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1. A Nested Case-Control Study of Metabolically Defined Body Size Phenotypes and Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Author: Murphy, N, Cross, A, Abubakar, M, Jenab, M, Aleksandrova, K, Boutron-Ruault, M, Dossus, L, Racine, A, Kühn, T, Katzke, V, Tjønneland, A, Petersen, K, Overvad, K, Quirós, JR, Jakszyn, P, Molina-Montes, E, Dorronsoro, M, Huerta, J, Barricarte, A, Khaw, K, Wareham, N, Travis, R, Trichopoulou, A, Lagiou, P, Trichopoulos, D, Masala, G, Krogh, V, Tumino, R, Vineis, P, Panico, S, Bueno-de-Mesquita, H, Siersema, P, Peeters, P, Ohlsson, B, Ericson, U, Palmqvist, R, Nyström, H, Weiderpass, E, Skeie, G, Freisling, H, Kong, S, Tsilidis, K, Muller, D, Riboli, E, Gunter, M, [Murphy,N, Cross,AJ, Vineis,P, Bueno-de-Mesquita,HB, Tsilidis,K, Riboli,E, Gunter,MJ] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.[Abubakar,M] Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, United Kingdom. [Jenab,M, Freisling,M, Kong,SY, Mulle,DC, Gunter,MJ] International Agency for Research on Cancer, World Health Organization, Lyon, France. [Aleksandrova,K] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Potsdam, Germany. [Boutron-Ruault,M, Dossus,L, Racine,A] Inserm, Nutrition, Hormones and Women’s Health, Centre for Research in Epidemiology and Population Health (CESP), U1018, Villejuif, France. Université Paris Sud, UMRS 1018, Villejuif, France. Institut Gustave Roussy, Villejuif, France. [Kühn,T, Katzke,VA] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Tjønneland,A, Petersen,KEN] Danish Cancer Society Research Center, Copenhagen, Denmark. [Overvad,K] Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark. [Quirós,JR] Public Health Directorate, Asturias, Spain. [Jakszyn,P] Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology, Barcelona, Spain. [Molina-Montes,E] Andalusian School of Public Health, Granada, Spain. [Molina-Montes,E, Huerta,J, Barricarte,A] Biomedical Research Centre Network for Epidemiology and Public Health (CIBERESP), Madrid, Spain. [Dorronsoro,M] Public Health Direction and Biodonostia–CIBERESP, Basque Regional Health Department, Vitoria, Spain. [Huerta,J] Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain. [Barricarte,A] Navarre Public Health Institute, Pamplona, Spain. [Khaw,K] University of Cambridge, Cambridge, United Kingdom. [Wareham,N] MRC Epidemiology Unit, Cambridge, United Kingdom. [Travis,RC] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. [Trichopoulou,A, Trichopoulos,D] Hellenic Health Foundation, Athens, Greece. [Trichopoulou,A, Lagiou,P] Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. [Trichopoulou,A, Lagiou,P, Trichopoulos,D] Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. [Lagiou,P, Trichopoulos,D] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America. [Masala,G] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy. [Krogh,V] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Tumino,R] Cancer Registry and Histopathology Unit, Civic–M.P.Arezzo Hospital, Azienda Sanitaria Provinciale di Ragusa, Italy. [Vineis,P] HuGeF Foundation, Torino, Italy. [Panico,S] Dipartimento di Medicina Clinica e Sperimentale, Federico II University, Naples, Italy. [Bueno-de- Mesquita,HB] Department of Determinants of Chronic Diseases, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia [Bueno-de-Mesquita,HB, Siersema,PD] Department of Gastroenterology and Hepatology, University Medical Centre Utrecht, Utrecht, The Netherlands. [Peeters,PH] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. [Ohlsson,B] Division of Internal Medicine, Department of Clinical Sciences, Skåne University Hospital, Lund University, Malmö, Sweden. [Ericson,U] Diabetes and Cardiovascular Disease–Genetic Epidemiology, Department of Clinical Sciences, Skåne University Hospital, Lund University, Malmö, Lund University, Sweden. [Palmqvist,R, Nyström,H] Medical Bioscience, Umeå University, Umeå, Sweden. [Weiderpass,E, Skeie,G] Department of Community Medicine, Faculty of Health Sciences, University of Tromsø–The Arctic University of Norway, Tromsø, Norway. [Weiderpass,E] Cancer Registry of Norway, Oslo, Norway. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Department of Genetic Epidemiology, Folkhälsan Research Center, Helsinki, Finland. [Tsilidis,K] Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece., Funding: The coordination of EPIC is financially supported by the European Commission (DGSANCO), and the International Agency for Research on Cancer., University Medical Center Utrecht, Imperial College Trust, Murphy, Neil, Cross, Amanda J, Abubakar, Mustapha, Jenab, Mazda, Aleksandrova, Krasimira, Boutron Ruault, Marie Christine, Dossus, Laure, Racine, Antoine, Kühn, Tilman, Katzke, Verena A, Tjønneland, Anne, Petersen, Kristina E. N, Overvad, Kim, Quirós, J. Ramón, Jakszyn, Paula, Molina Montes, Esther, Dorronsoro, Miren, Huerta, José María, Barricarte, Aurelio, Khaw, Kay Tee, Wareham, Nick, Travis, Ruth C, Trichopoulou, Antonia, Lagiou, Pagona, Trichopoulos, Dimitrio, Masala, Giovanna, Krogh, Vittorio, Tumino, Rosario, Vineis, Paolo, Panico, Salvatore, Bueno de Mesquita, H. Ba, Siersema, Peter D, Peeters, Petra H, Ohlsson, Bodil, Ericson, Ulrika, Palmqvist, Richard, Nyström, Hanna, Weiderpass, Elisabete, Skeie, Guri, Freisling, Heinz, Kong, So Yeon, Tsilidis, Kosta, Muller, David C, Riboli, Elio, Gunter, Marc J., Khaw, Kay-Tee [0000-0002-8802-2903], Wareham, Nicholas [0000-0003-1422-2993], and Apollo - University of Cambridge Repository
Subjects: Male, Phenomena and Processes::Genetic Phenomena::Phenotype [Medical Subject Headings], Cell- och molekylärbiologi, Obesidad, Biochemistry, Body Mass Index, Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14], Endocrinology, Odds Ratio, Insulin, Prospective Studies, Diseases::Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Body Weight::Overweight [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Vital Statistics::Morbidity::Prevalence [Medical Subject Headings], Adiposity, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, C-Peptide, Incidence, 11 Medical And Health Sciences, Oncology, Medicine, Waist Circumference, Fenotipo, Human, Logistic Model, Colon, Risk Assessment, Hyperinsulinism, Gastrointestinal Tumors, Neoplasias Colorrectales, Humans, Comparative Study, Diseases::Cardiovascular Diseases [Medical Subject Headings], Protective Factor, Cancer och onkologi, Chi-Square Distribution, Biology and Life Sciences, nutritional and metabolic diseases, Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [Medical Subject Headings], Biomarker, Hormones, Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::Obesity [Medical Subject Headings], Prospective Studie, Logistic Models, Case-Control Studies, Cancer and Oncology, Digestive System, Biomarkers, Cell and Molecular Biology, Metabolic Processes, Physiology, Health Status, Colorectal Neoplasm, Health Statu, Risk Factors, Medicine and Health Sciences, Body Size, Multivariate Analysi, Tamaño Corporal, Enfermedades Cardiovasculares, Medicine(all), Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings], Research Support, Non-U.S. Gov't, Estudios de Casos y Controles, Estudios Prospectivos, Middle Aged, Multicenter Study, Europe, Phenotype, Physiological Parameters, Female, Anatomy, Colorectal Neoplasms, Case-Control Studie, Research Article, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Physical Examination::Body Constitution::Body Weights and Measures::Body Size [Medical Subject Headings], Rectal Cancer, Research Support, N.I.H., Extramural, General & Internal Medicine, Journal Article, Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Hyperinsulinism [Medical Subject Headings], Obesity, Colorectal Cancer, Diabetic Endocrinology, Obesity, Metabolically Benign, Hiperinsulinismo, Risk Factor, Body Weight, Cancers and Neoplasms, Protective Factors, Gastrointestinal Tract, Metabolism, Sobrepeso, Multivariate Analysis, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, Prevalencia
Abstract: Background Obesity is positively associated with colorectal cancer. Recently, body size subtypes categorised by the prevalence of hyperinsulinaemia have been defined, and metabolically healthy overweight/obese individuals (without hyperinsulinaemia) have been suggested to be at lower risk of cardiovascular disease than their metabolically unhealthy (hyperinsulinaemic) overweight/obese counterparts. Whether similarly variable relationships exist for metabolically defined body size phenotypes and colorectal cancer risk is unknown. Methods and Findings The association of metabolically defined body size phenotypes with colorectal cancer was investigated in a case–control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Metabolic health/body size phenotypes were defined according to hyperinsulinaemia status using serum concentrations of C-peptide, a marker of insulin secretion. A total of 737 incident colorectal cancer cases and 737 matched controls were divided into tertiles based on the distribution of C-peptide concentration amongst the control population, and participants were classified as metabolically healthy if below the first tertile of C-peptide and metabolically unhealthy if above the first tertile. These metabolic health definitions were then combined with body mass index (BMI) measurements to create four metabolic health/body size phenotype categories: (1) metabolically healthy/normal weight (BMI < 25 kg/m2), (2) metabolically healthy/overweight (BMI ≥ 25 kg/m2), (3) metabolically unhealthy/normal weight (BMI < 25 kg/m2), and (4) metabolically unhealthy/overweight (BMI ≥ 25 kg/m2). Additionally, in separate models, waist circumference measurements (using the International Diabetes Federation cut-points [≥80 cm for women and ≥94 cm for men]) were used (instead of BMI) to create the four metabolic health/body size phenotype categories. Statistical tests used in the analysis were all two-sided, and a p-value of, Gunter and colleagues analyse a large European dataset to determine how body size and metabolic profile associates with the risk of developing colorectal cancer., Editors' Summary Background Colorectal cancer is the third most common cancer worldwide and is a leading cause of cancer-related death, killing around 700,000 people every year. It develops when cells in the colon (the final part of the digestive system, which is also known as the large intestine or large bowel) or the rectum (the lower end of the colon) acquire genetic changes that allow them to divide uncontrollably to form a tumor and to move around the body (metastasize). Symptoms of colorectal cancer include blood in the stool, a change in bowel habits, and unexplained weight loss. Treatments for colorectal cancer include surgery, chemotherapy, and radiation. As with other types of cancer, these treatments are more likely to be successful if started when the tumor is very small. Consequently, many countries run screening programs that use colonoscopy, the fecal occult blood test, and other tests to detect the earliest signs of colorectal cancer in apparently healthy people. Why Was This Study Done? Being obese—having too much body fat—is associated with an increased colorectal cancer risk (other risk factors include age, having a family history of colorectal cancer, and eating a high-fat, low-fiber diet). Obesity is also associated with several other chronic diseases, and recent evidence suggests that some obese individuals have a higher risk of developing these diseases than others. For example, overweight/obese individuals who have hyperinsulinemia (abnormally high blood levels of insulin; “metabolically unhealthy”) seem to have a higher risk of cardiovascular disease than their non-hyperinsulinemic (“metabolically healthy”) overweight counterparts. If certain combinations of metabolic health status and body size (“metabolically defined body size phenotypes”) are also associated with colorectal cancer, measurement of insulin levels in conjunction with body fat (adiposity) measurements such as body mass index (BMI; an indicator of body fat calculated by dividing a person’s weight in kilograms by their height in meters squared) might improve colorectal cancer risk assessment. In this nested case–control study, the researchers assess the associations between metabolically defined body size phenotypes and colorectal cancer risk. A nested case–control study identifies everyone in a group (here, participants in the European Prospective Investigation into Cancer and Nutrition [EPIC] study) who has a specific condition, identifies matched individuals in the same group without the condition, and asks whether these controls and the cases differ in terms of a specific characteristic or outcome. What Did the Researchers Do and Find? The researchers matched 737 participants in the EPIC study who developed colorectal cancer after study enrollment with 737 controls and used serum concentrations of C-peptide, a marker of insulin secretion, and BMI measurements to classify each individual as metabolically healthy/normal weight, metabolically healthy/overweight, metabolically unhealthy/normal weight, or metabolically unhealthy/overweight. Specifically, the researchers categorized people as metabolically unhealthy if they had a C-peptide level above an arbitrarily chosen cut-off value based on the distribution of C-peptide levels in the control participants and as overweight if they had a BMI of ≥25 kg/m2 (the standard definition of overweight). Compared to metabolically healthy normal weight individuals, metabolically unhealthy normal weight and overweight individuals had an increased colorectal cancer risk; metabolically healthy overweight individuals had a similar colorectal cancer risk to metabolically healthy normal weight individuals. Among overweight individuals, metabolically healthy individuals had a lower colorectal cancer risk than metabolically unhealthy individuals. Finally, similar associations were seen when the researchers used waist circumference instead of BMI as the measure of adiposity. What Do These Findings Mean? These findings suggest that normal weight individuals with hyperinsulinemia (the metabolically unhealthy normal weight phenotype) have a higher risk of colorectal cancer than normal weight individuals without hyperinsulinemia. They also suggest that metabolically unhealthy overweight individuals have a higher risk of colorectal cancer than metabolically healthy overweight individuals. The accuracy of these findings may be limited by the method the researchers used to classify individuals as hyperinsulinemic—there is no universally accepted clinical definition for using C-peptide level to diagnose hyperinsulinemia. Nevertheless, these findings suggest that the assessment of insulin levels in conjunction with adiposity measures might be a better way to assess an individual’s colorectal cancer risk than simply measuring adiposity, and might help to identify those individuals at high risk of colorectal cancer who are most likely to benefit from targeted interventions designed to prevent the onset of clinical disease. Additional Information This list of resources contains links that can be accessed when viewing the PDF on a device or via the online version of the article at http://dx.doi.org/10.1371/journal.pmed.1001988. The US National Cancer Institute provides information for patients about all aspects of colorectal cancer; it also provides more detailed information colorectal cancer for health professionals and information on cancer risk and obesity The UK National Health Service Choices website has information and personal stories about colorectal cancer and information on obesity The not-for-profit organization Cancer Research UK provides information about colorectal cancer and about the association between cancer and obesity MedlinePlus provides links to further resources about colorectal cancer and about obesity Wikipedia has a page on hyperinsulinemia (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages) More information about the EPIC study is available
Published: 2016

2. Alcohol drinking and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Author: Fedirko, V, Jenab, M, Rinaldi, S, Biessy, C, Allen, NE, Dossus, L, Onland-Moret, NC, Schütze, M, Tjønneland, A, Hansen, L, Overvad, K, Clavel-Chapelon, F, Chabbert-Buffet, N, Kaaks, R, Lukanova, A, Bergmann, MM, Boeing, H, Trichopoulou, A, Oustoglou, E, Barbitsioti, A, Saieva, C, Tagliabue, G, Galasso, R, Tumino, R, Sacerdote, C, Peeters, PH, Bueno-de-Mesquita, HB, Weiderpass, E, Gram, IT, Sanchez, S, Duell, EJ, Molina-Montes, E, Arriola, L, Chirlaque, MD, Ardanaz, E, Manjer, J, Lundin, E, Idahl, A, Khaw, KT, Romaguera-Bosch, D, Wark, PA, Norat, T, and Romieu, I
Subjects: Adult, Oncology, medicine.medical_specialty, Alcohol Drinking, Epidemiology, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Surveys and Questionnaires, Internal medicine, Confidence Intervals, Odds Ratio, Humans, Medicine, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Life Style, Aged, Proportional Hazards Models, Gynecology, business.industry, Proportional hazards model, Alcoholic Beverages, Incidence, Incidence (epidemiology), Endometrial cancer, Odds ratio, Middle Aged, medicine.disease, Endometrial Neoplasms, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, Socioeconomic Factors, 030220 oncology & carcinogenesis, Female, business, Hormone, Cohort study
Abstract: Purpose: Alcohol intake may adversely affect the concentrations of endogenous sex hormones, and thus increase the risk of endometrial cancer. However, epidemiologic studies have provided conflicting results. Therefore, we investigated the association between alcohol intake and endometrial cancer risk a large, multicenter, prospective study. Methods: From 1992 through 2010, 301,051 women in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort were followed for incident endometrial cancer (n = 1382). Baseline alcohol consumption was assessed by country-specific, validated dietary questionnaires. Information on past alcohol consumption was collected by lifestyle questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from Cox proportional hazard models. Results: The multivariable HRs (and 95% CIs) compared with light drinkers (0.1-6 g/d) were 1.03 (0.88-1.20) for 0 g of alcohol per day at baseline, 1.01 (0.86-1.17) for 6.1-12 g/d, 1.03 (0.87-1.22) for 12.1-24 g/d, 1.07 (0.87-1.38) for 24.1-36 g/d, and 0.85 (0.61-1.18) for more than 36 g/d (ptrend = 0.77). No association was observed among former drinkers (OR, 1.28; 95% CI, 0.98-1.68 compared with light drinkers). Null associations were also found between alcohol consumption at age 20 years, lifetime pattern of alcohol drinking, and baseline alcohol intake from specific alcoholic beverages and endometrial cancer risk. Conclusions: Our findings suggest no association between alcohol intake and endometrial cancer risk. © 2013 Elsevier Inc.
Published: 2016

3. Healthy Lifestyle and Risk of Cancer in the European Prospective Investigation Into Cancer and Nutrition Cohort Study

Author: McKenzie, F, Biessy, C, Ferrari, P, Freisling, H, Rinaldi, S, Chajès, V, Dahm, C, Overvad, K, Dossus, L, Lagiou, P, Trichopoulos, D, Trichopoulou, A, Bueno-de-Mesquita, H, May, A, Peeters, P, Weiderpass, E, Sanchez, M, Navarro, C, Ardanaz, E, Ericson, U, Wirfält, E, Travis, R, Romieu, I, de Batlle, J, Dartois, L, Krogh, V, Panico, S, Tumino, R, Rosso, S, Buckland, G, Andersson, A, Sund, M, Key, T, Gunter, M, Riboli, E, Vergnaud, A, and Medical Research Council (MRC)
Subjects: Gerontology, Male, Health Status, GUIDELINES, 0302 clinical medicine, Behavior Therapy, Neoplasms, Medicine, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, Non-U.S. Gov't, INDEX, Cancer, Medicine(all), education.field_of_study, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, Nutritional Support, Research Support, Non-U.S. Gov't, Hazard ratio, Age Factors, WOMEN, General Medicine, Middle Aged, Nutrition Surveys, Prognosis, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, Multicenter Study, 030220 oncology & carcinogenesis, Cohort, Female, CONCORDANCE, Life Sciences & Biomedicine, RESEARCH FUND/AMERICAN INSTITUTE, Cohort study, Research Article, Adult, Population, Observational Study, Lower risk, Research Support, Risk Assessment, DIET, 03 medical and health sciences, Medicine, General & Internal, Sex Factors, General & Internal Medicine, Journal Article, Humans, CORONARY-HEART-DISEASE, education, Life Style, METAANALYSIS, Science & Technology, Cancer prevention, business.industry, Prevention, 1103 Clinical Sciences, PREVENTION, Arthritis & Rheumatology, Life style, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business, Demography, Follow-Up Studies, Forecasting
Abstract: It has been estimated that at least a third of the most common cancers are related to lifestyle and as such are preventable. Key modifiable lifestyle factors have been individually associated with cancer risk; however, less is known about the combined effects of these factors. This study generated a healthy lifestyle index score (HLIS) to investigate the joint effect of modifiable factors on the risk of overall cancers, alcohol-related cancers, tobacco-related cancers, obesity-related cancers, and reproductive-related cancers. The study included 391,608 men and women from the multinational European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The HLIS was constructed from 5 factors assessed at baseline (diet, physical activity, smoking, alcohol consumption, and anthropometry) by assigning scores of 0 to 4 to categories of each factor, for which higher values indicate healthier behaviors. Hazard ratios (HR) were estimated by Cox proportional regression and population attributable fractions (PAFs) estimated from the adjusted models. There was a 5% lower risk (adjusted HR 0.952, 95% confidence interval (CI): 0.946, 0.958) of all cancers per point score of the index for men and 4% (adjusted HR 0.961, 95% CI: 0.956, 0.966) for women. The fourth versus the second category of the HLIS was associated with a 28% and 24% lower risk for men and women respectively across all cancers, 41%and 33%for alcohol-related, 49%and 46%for tobacco-related, 41% and 26% for obesity-related, and 21% for female reproductive cancers. Findings suggest simple behavior modifications could have a sizeable impact on cancer prevention, especially for men.
Published: 2016

4. Height, age at menarche and risk of hormone receptor-positive and -negative breast cancer: a cohort study

Author: Ritte, R, Lukanova, A, Tjønneland, A, Olsen, A, Overvad, K, Mesrine, S, Fagherazzi, G, Dossus, L, Teucher, B, Steindorf, K, Boeing, H, Aleksandrova, K, Trichopoulou, A, Lagiou, P, Trichopoulos, D, Palli, D, Grioni, S, Mattiello, A, Tumino, R, Sacerdote, C, Quirõs, JR, Buckland, G, Molina-Montes, E, Chirlaque, MD, Ardanaz, E, Amiano, P, Bueno-De-Mesquita, B, Van Duijnhoven, F, Van Gils, CH, Peeters, PH, Wareham, N, Khaw, KT, Key, TJ, Travis, RC, Krum-Hansen, S, Gram, IT, Lund, E, Sund, M, Andersson, A, Romieu, I, Rinaldi, S, McCormack, V, Riboli, E, and Kaaks, R
Subjects: Cancer Research, Nutrition and Disease, population, Physiology, exposures, Risk Factors, Voeding en Ziekte, Prospective Studies, Prospective cohort study, estrogen-receptor, education.field_of_study, Age Factors, Middle Aged, Prognosis, European Prospective Investigation into Cancer and Nutrition, Europe, Receptors, Estrogen, Oncology, Cohort, Menarche, Female, Receptors, Progesterone, associations, Adult, medicine.medical_specialty, body-size, growth, Population, Breast Neoplasms, Breast cancer, Biomarkers, Tumor, medicine, Humans, Risk factor, education, VLAG, childhood, Gynecology, Leg, leg length, business.industry, Proportional hazards model, Estrogens, medicine.disease, Body Height, adolescence, participants, business, Follow-Up Studies
Abstract: Associations of breast cancer overall with indicators of exposures during puberty are reasonably well characterized; however, uncertainty remains regarding the associations of height, leg length, sitting height and menarcheal age with hormone receptor-defined malignancies. Within the European Prospective Investigation into Cancer and Nutrition cohort, Cox proportional hazards models were used to describe the relationships of adult height, leg length and sitting height and age at menarche with risk of estrogen and progesterone receptor negative (ER-PR-) (n = 990) and ER+PR+ (n = 3,524) breast tumors. Height as a single risk factor was compared to a model combining leg length and sitting height. The possible interactions of height, leg length and sitting height with menarche were also analyzed. Risk of both ER-PR- and ER+PR+ malignancies was positively associated with standing height, leg length and sitting height and inversely associated with increasing age at menarche. For ER+PR+ disease, sitting height (hazard ratios: 1.14[95% confidence interval: 1.08-1.20]) had a stronger risk association than leg length (1.05[1.00-1.11]). In comparison, for ER-PR- disease, no distinct differences were observed between leg length and sitting height. Women who were tall and had an early menarche (≤13 years) showed an almost twofold increase in risk of ER+PR+ tumors but no such increase in risk was observed for ER-PR- disease. Indicators of exposures during rapid growth periods were associated with risks of both HR-defined breast cancers. Exposures during childhood promoting faster development may establish risk associations for both HR-positive and -negative malignancies. The stronger associations of the components of height with ER+PR+ tumors among older women suggest possible hormonal links that could be specific for postmenopausal women. What's new? Adult height and early age at menarche are established risk factors for breast cancer. In this study, the authors examined these factors in relation to the hormone-receptor status of breast tumors, with height divided into leg length vs. sitting height. They found that women who were tall and had an early menarche (≤13 years) had almost double the risk of developing estrogen/progesterone-positive (ER+PR+) tumors. Leg length and early menarche were also associated with increased risk for receptor-negative (ER-PR-) tumors. In addition, the data suggest possible hormonal links that could be specific for postmenopausal women. Copyright © 2012 UICC.
Published: 2013

5. Comprehensive analysis of hormone and genetic variation in 36 genes related to steroid hormone metabolism in pre- and postmenopausal women from the breast and prostate cancer cohort consortium (BPC3)

Author: Beckmann, L., Hüsing, A., Setiawan, V. W., Amiano, P., Clavel-Chapelon, F., Chanock, S. J., Cox, D. G., Diver, R., Dossus, L., Feigelson, H. S., Haiman, C., Hallmans, G., Hayes, R. B., Henderson, B. E., Hoover, R. N., Hunter, D. J., Khaw, K., Kolonel, L. N., Kraft, P., Lund, E., Le Marchand, L., Peeters, P. H. M., Riboli, E., Stram, D., Thomas, G., Thun, M. J., Tumino, R., Trichopoulos, D., Vogel, U., Willett, W. C., Yeager, M., Ziegler, R., Hankinson, S. E., Kaaks, R., Renseigné, Non, Public Health Division of Gipuzkoa, Basque Government, CIBER en Salud Pública, CIBERSP, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Gustave Roussy (IGR), Equipe 06, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Public Health and Clinical Medicine, Nutritional Research, Umeå University, Division of Epidemiology, Public Health and Primary Care, Imperial College London, Laboratoire des Procédés en Milieux Granulaires (LPMG-EMSE), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)-Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Civile - M.P.Arezzo Hospital, Department Cancer Epidemiology, and German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ)
Subjects: Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Clinical Biochemistry, MESH: Risk Assessment, Biochemistry, Body Mass Index, Cohort Studies, 0302 clinical medicine, Endocrinology, Sex hormone-binding globulin, MESH: Hormones, Ethnicity, polycyclic compounds, Hormone metabolism, Prospective cohort study, Gonadal Steroid Hormones, MESH: Cohort Studies, Testosterone, MESH: Genetic Association Studies, MESH: Gonadal Steroid Hormones, MESH: Aged, 0303 health sciences, MESH: Middle Aged, biology, MESH: Polymorphism, Single Nucleotide, Age Factors, MESH: Genetic Predisposition to Disease, Middle Aged, 3. Good health, Europe, Postmenopause, MESH: Premenopause, 030220 oncology & carcinogenesis, Cohort, Female, Steroids, MESH: Ethnic Groups, hormones, hormone substitutes, and hormone antagonists, MESH: Postmenopause, Cohort study, medicine.medical_specialty, endocrine system, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Polymorphism, Single Nucleotide, Risk Assessment, MESH: Body Mass Index, 03 medical and health sciences, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, Alleles, Genetic Association Studies, 030304 developmental biology, Aged, MESH: Age Factors, MESH: Humans, MESH: Alleles, Biochemistry (medical), JCEM Online: Brief Reports, Hormones, MESH: Steroids, Steroid hormone, Premenopause, biology.protein, MESH: Europe, MESH: Female, Steroid hormone metabolism, MESH: Breast Neoplasms
Abstract: International audience; CONTEXT: Sex steroids play a central role in breast cancer development. OBJECTIVE: This study aimed to relate polymorphic variants in 36 candidate genes in the sex steroid pathway to serum concentrations of sex steroid hormones and SHBG. DESIGN: Data on 700 genetic polymorphisms were combined with existing hormone assays and data on breast cancer incidence, within the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Nurses' Health Study (NHS) cohorts; significant findings were reanalyzed in the Multiethnic Cohort (MEC). SETTING AND PARTICIPANTS: We analyzed data from a pooled sample of 3852 pre- and postmenopausal Caucasian women from EPIC and NHS and 454 postmenopausal women from MEC. MAIN OUTCOME MEASURES: Outcome measures were SHBG, testosterone, dehydroepiandrosterone (DHEAS), androstenedione, estrone (E1), and estradiol (E2) as well as breast cancer risk. RESULTS: Globally significant associations were found among pre- and postmenopausal women combined between levels of SHBG and the SHBG gene and between DHEAS and the FSHR and AKR1C3 genes. Among postmenopausal women, serum E1 and E2 were significantly associated with the genes CYP19 and FSHR, and E1 was associated with ESR1. None of the variants related to serum hormone levels showed any significant association with breast cancer risk. CONCLUSIONS: We confirmed associations between serum levels of SHBG and the SHBG gene and of E1 and E2 and the CYP19 and ESR1 genes. Novel associations were observed between FSHR and DHEAS, E1, and E2 and between AKR1C3 and DHEAS.
Published: 2011

6. Diabetes mellitus, glycated haemoglobin and C-peptide levels in relation to pancreatic cancer risk; a study within the prospective EPIC cohort

Author: Grote, VA, Rohrmann, S, Nieters, A, Dossus, L, Bueno-de-Mesquita, HB, and Kaaks, R
Subjects: ddc: 610, diabetes, pancreatic cancer, cohort study, glycated haemoglobin, C-peptide, 610 Medical sciences, Medicine, EPIC
Abstract: Background: It is a long-standing debate whether diabetes mellitus is a potentially causal risk factor for pancreatic cancer, or more likely a consequence of pancreatic tumour development. Prospective epidemiologic studies have shown variable relationships of pancreas cancer risk with pre-diagnostic[for full text, please go to the a.m. URL], Mainz//2011; 56. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie (gmds), 6. Jahrestagung der Deutschen Gesellschaft für Epidemiologie (DGEpi)
Published: 2011
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7. Circulating prolactin and in situ breast cancer risk in the European EPIC cohort: a case-control study

Author: Sabina Rinaldi, Aurelio Barricarte, Dimitrios Trichopoulos, Evelyn M. Monninkhof, Françoise Clavel-Chapelon, Anne Tjønneland, Amalia Mattiello, Laure Dossus, Renée T. Fortner, Virginia Menéndez, Vittorio Krogh, Kim Overvad, Fulvio Ricceri, Antonia Trichopoulou, Rosario Tumino, Laura Baglietto, Kaja Tikk, Elisabete Weiderpass, Disorn Sookthai, Ruth C. Travis, Timothy J. Key, María José Sánchez, Antonio Agudo, Giovanna Masala, Isabelle Romieu, Elio Riboli, Heiner Boeing, María Dolores Chirlaque, Malin Sund, Theron Johnson, Anja Olsen, N. Charlotte Onland-Moret, Anne Andresson, Rudolf Kaaks, Hbas Bueno-de-Mesquita, Pagona Lagiou, Pilar Amiano, Kay-Tee Khaw, Melissa A. Merritt, [Tikk,K, Sookthai,D, Fortner,RT, Johnson,T, Kaaks,R] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Rinaldi,S, Romieu,I] Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC), Lyon, France. [Tjønneland,D, Olsen,A] Danish Cancer Society Research Center, Copenhagen, Denmark. [Overvad,K] Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark. [Clavel-Chapelon,F, Dossus,l] INSERM, Centre for Research in Epidemiology and Population Health [CESP], Nutrition, Hormones and Women’s Health team, Villejuif, France. [Clavel-Chapelon,F, Dossus,l] Univ Paris Sud, Villejuif, France. [Clavel-Chapelon,F, Dossus,l] IGR, Villejuif, France. [Baglietto,L] Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia. Centre for Molecular, Environmental, Genetic, and Analytic Epidemiology, The University of Melbourne, Melbourne, Australia. [Boeing,H] Department of Epidemiology, German Institute of Human Nutrition (DIfE) Potsdam-Rehbrücke, Nuthetal, Germany. [Trichopoulou,A, Trichopoulos,D] Hellenic Health Foundation, Athens, Greece.[Trichopoulou,A, Lagiou.P] Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Goudi, Athens, Greece. [Trichopoulou,A, Lagiou,P, Trichopoulos,D] Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. [Lagiou,P, Trichopoulos,D] Department of Epidemiology, Harvard School of Public Health, Boston, USA. [Masala,G] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute, Florence, Italy. [Krogh,V] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. [Tumino,R] Cancer Registry and Histopathology Unit, 'Civic - M.P.Arezzo' Hospital ASP, Ricceri, Ragusa, Italy. [Ricceri,F] Unit of Cancer Epidemiology, AO Citta’ della Salute e della Scienza, University of Turin, Torino, Italy. Unit of Cancer Epidemiology, AO Citta’ della Salute e della Scienza, University of Turin, Torino, Italy. [Mattiello,A] Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy. [Agudo,A] Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology-ICO, IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain. [Menéndez,V] Public Health Directorate, Asturias, Spain. [Sánchez,M] Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitario de Granada (Granada.ibs), Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain. [Amiano,P] Public Health Division of Gipuzkoa, BioDonostia Reserach Institute, San Sebastian, Spain. [Chirlaque,M] Department of Epidemiology, Murcia Regional Health Authority, Murcia, Spain. [Barricarte,A] Navarre Public Health Institute, Pamplona, Spain. [Sánchez, M, Amiano, P, Chirlaque,M, Barricarte,A] Consortium for Biomedical Research in Epidemiology and Public Health (CIBER de Epidemiología y Salud Pública (CIBERESP)), Madrid, Spain. [Bueno-de-Mesquita,H] Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands. Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. [Bueno-de-Mesquita,H, Merritt,MA, Riboli,E] Department of Epidemiology and Biostatistics, The School of Public Health, Imperial College, London, UK. [Monninkhof,EM, Onland-Moret,NC] Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. [Andresson,A] Department of Radiation Sciences, University of Umeå, Umeå, Sweden. [Sund,M] Department of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden. [Weiderpass,E] Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway. Department of Research, Cancer Registry of Norway, Oslo, Norway. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Samfundet Folkhälsan, Helsinki, Finland, [Khaw,K] School of Clinical Medicine, University of Cambridge, Cambridge, UK. [Key,TJ, and Travis,RC] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK. [Tikk,K] Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ) Heidelberg, Heidelberg, Germany.
Subjects: Oncology, Cancer Research, Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Peptide Hormones::Gonadotropins::Gonadotropins, Pituitary::Prolactin [Medical Subject Headings], PERIOD, Prolactina, Cohort Studies, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Breast cancer, Risk Factors, REPRODUCIBILITY, HISTORY, Odds Ratio, 0303 health sciences, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings], Neoplasias de la Mama, Estudios de Casos y Controles, Middle Aged, Adult, Aged, Breast Neoplasms, Carcinoma in Situ, Case-Control Studies, Europe, Female, Follow-Up Studies, Humans, Logistic Models, Menopause, Prolactin, 3. Good health, European Prospective Investigation into Cancer and Nutrition, POSTMENOPAUSAL WOMEN, PREMENOPAUSAL WOMEN, 030220 oncology & carcinogenesis, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk [Medical Subject Headings], Cohort, Life Sciences & Biomedicine, Cohort study, Research Article, medicine.medical_specialty, CARCINOMA, STEROID-HORMONES, Riesgo, Càncer de mama, 03 medical and health sciences, Internal medicine, parasitic diseases, medicine, Journal Article, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], 030304 developmental biology, Cancer och onkologi, Science & Technology, business.industry, Carcinoma in situ, Case-control study, Odds ratio, medicine.disease, Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::Carcinoma::Carcinoma in Situ [Medical Subject Headings], Cancer and Oncology, PLASMA PROLACTIN, business
Abstract: Introduction The relationship between circulating prolactin and invasive breast cancer has been investigated previously, but the association between prolactin levels and in situ breast cancer risk has received less attention. Methods We analysed the relationship between pre-diagnostic prolactin levels and the risk of in situ breast cancer overall, and by menopausal status and use of postmenopausal hormone therapy (HT) at blood donation. Conditional logistic regression was used to assess this association in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, including 307 in situ breast cancer cases and their matched control subjects. Results We found a significant positive association between higher circulating prolactin levels and risk of in situ breast cancer among all women [pre-and postmenopausal combined, ORlog2 = 1.35 (95% CI 1.04-1.76), P-trend = 0.03]. No statistically significant heterogeneity was found between prolactin levels and in situ cancer risk by menopausal status (P-het = 0.98) or baseline HT use (P-het = 0.20), although the observed association was more pronounced among postmenopausal women using HT compared to non-users (P-trend = 0.06 vs P-trend = 0.35). In subgroup analyses, the observed positive association was strongest in women diagnosed with in situ breast tumors = 4 years after blood donation (P-trend = 0.01 vs P-trend = 0.63; P-het = 0.04) and among nulliparous women compared to parous women (P-trend = 0.03 vs P-trend = 0.15; P-het = 0.07). Conclusions Our data extends prior research linking prolactin and invasive breast cancer to the outcome of in situ breast tumours and shows that higher circulating prolactin is associated with increased risk of in situ breast cancer.The relationship between circulating prolactin and invasive breast cancer has been investigated previously, but the association between prolactin levels and in situ breast cancer risk has received less attention.
Published: 2015

8. Sources of pre-analytical variations in yield of DNA extracted from blood samples: analysis of 50,000 DNA samples in EPIC

Author: Domenico Palli, Bertrand Hémon, Petra H.M. Peeters, Guri Skeie, Gilles Ferro, Pierre Hainaut, Françoise Clavel-Chapelon, Karina Standahl Olsen, Amy Hutchinson, Carine Biessy, Elio Riboli, Afshan Siddiq, Antonia Trichopoulou, Pagona Lagiou, Christophe Lallemand, Nicholas J. Wareham, Federico Canzian, Heiner Boeing, Anne Boland, Claudia Agnoli, Roberto Bilbao, Elodie Caboux, Eiliv Lund, Ruth C. Travis, Carmen Navarro, Maimuna Mendy, Núria Sala, Laure Dossus, Eva Fisher, Dimitrios Trichopoulos, Aurelio Barricarte, Yvonne T. van der Schouw, Maria Luisa Redondo, H. Bas Bueno-de-Mesquita, Isabelle Romieu, Rosario Tumino, Marie-Christine Boutron-Ruault, Salvatore Panico, Abigail Britten, Paolo Vineis, Silvia Polidoro, Mark J. Gunter, Sabina Rinaldi, María José Sánchez, Matthew A. Sims, International Prevention Research Institute (IPRI), Caboux, E, Lallemand, C, Ferro, G, H?mon, B, Mendy, M, Biessy, C, Sims, M, Wareham, N, Britten, A, Boland, A, Hutchinson, A, Siddiq, A, Vineis, P, Riboli, E, Romieu, I, Rinaldi, S, Gunter, Mj, Peeters, Ph, van der Schouw, Yt, Travis, R, Bueno de Mesquita, Hb, Canzian, F, S?nchez, Mj, Skeie, G, Olsen, K, Lund, E, Bilbao, R, Sala, N, Barricarte, A, Palli, D, Navarro, C, Panico, Salvatore, Redondo, Ml, Polidoro, S, Dossus, L, Boutron Ruault, Mc, Clavel Chapelon, F, Trichopoulou, A, Trichopoulos, D, Lagiou, P, Boeing, H, Fisher, E, Tumino, R, Agnoli, C, Hainaut, P., [Caboux,E, Lallemand,C, Ferro,G, Hémon,B, Mendy,M, Biessy,C, Romieu,I, Rinaldi,S] International Agency for Research on Cancer, Lyon, France. [Sims,M, Wareham,N, Britten,A] Medical Research Council (MRC) Epidemiology Unit, Addenbrooke’s Hospital, Cambridge, United Kingdom. [Boland,A] Centre National de Génotypage, Institut Génomique, Commissariat à l’énergie Atomique, Evry, France. [Hutchinson,A] Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department Health and Human Services, Bethesda, Maryland, United States of America. [Siddiq,A, Vineis,P, Riboli,E, Gunter,MJ, Peeters,PHM] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, United Kingdom. [Peeters,PHM, Schouw,T] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. [Travis,R[ Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom. [Bueno-de-Mesquita,HB] National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands. [Canzian,F] Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Sánchez,M] Andalusian School of Public Health, Granada (Spain) and CIBER de Epidemiología y Salud Pública (CIBERESP), Granada, Spain. [Skeie,G, Olsen,KS, Lund,E] Institute of Community Medicine, University of Tromsø, Tromsø, Norway. [Bilbao,R] Fundación Vasca de Innovación e Investigación Sanitarias, Sondika, Bizkaia, Spain. [Sala,N] Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology (ICO)-IDIBELL, Barcelona, Spain. [Barricarte,A] Navarre Public Health Institute, Pamplona, Spain. [Barricarte,A, Navarro,C] Consortium for Biomedical Research in Epidemiology and Public Health (CIBER Epidemiología y Salud Pública-CIBERESP), Madrid, Spain. [Hainaut,P] International Prevention Research Institute, Lyon, France. [Palli,D] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute – ISPO, Florence, Italy. [Navarro,C] Department of Epidemiology, Regional Health Authority, Murcia, Spain. [Panico,S] Department of clinical and experimental medicine, Federico ii University, Naples, Italy. [Redondo,ML] Public Health Directorate, Asturias, Spain. [Polidoro,S] Human Genetics Foundation-HuGeF, Turin, Italy. [Dossus,L, Boutron-Ruault,MC, Clavel-Chapelon,F] INSERM U1018, Gustave Roussy Institute, Paris South University, Villejuif, France. [Trichopoulou,A, Lagiou,P] Department of Hygiene, Epidemiology and Medical Statistics, Medical School, World Health Organization (WHO) Collaborating Center for Food and Nutrition Policies, University of Athens, Goudi, Athens, Greece. [Trichopoulou,A, Trichopoulos,D] Hellenic Health Foundation, Athens, Greece. [Trichopoulos,D, Lagiou,P] Department of Epidemiology, Harvard School of Public Health, Massachusetts, Boston, United States of America. Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. [Boeing,H] Potsdam-Rehbrücke Department of Epidemiology, German Institute of Human Nutrition (DIfE), Nuthetal, Germany. [Fisher,E] Administrative Office of the Commission on Genetic Testing Robert Koch-Institute, Berlin, Germany. [Tumino,R] Cancer Registry and Histopathology Unit, ‘‘Civile M. P. Arezzo’’ Hospital, Ragusa, Italy. [Agnoli,C] Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Funding: The study was funded by European Commission Research & Innovation DG project BBMRI (Biobanking and Biomolecular Resources Research Infrastructure,http://www.bbmri.eu), project number 212111 and by the Regular Budget of International Agency for Research on Cancer (IARC). DNA extraction data used in the study were generated as part of molecular epidemiological studies approved by the Steering Committee of the European Prospective Investigation into Cancer and Nutrition (EPIC, http://epic.iarc.fr). Detailed information about the funding of EPIC is available at http://epic.iarc.fr/funding.php. The funding agencies and organizations which provided funds for DNA extraction in specific EPIC studies were Imperial College London (ICL, BRCD study), Medical Research Council UK (MRC UK, EPHD study), European Community INTERACT project (through MRC Cambridge, UK, INT study, http://www.inter-act.eu), International Agency for Research on Cancer (IARC) and Imperial College London (ICL) (LUND study), EU FP6 Network of Excellence Environmental Cancer Risk, Nutrition and Individual Susceptibility (ECNIS, http:// www.ecnis.org), and and Cancer Research UK (CRCUK) (LYMD study).
Subjects: Male, Erythrocytes, Genotyping Techniques, Epidemiology, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Errors::Observer Variation [Medical Subject Headings], ADN, Genome-wide association study, Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Biochemistry, Body Mass Index, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Anatomy::Cells::Blood Cells::Erythrocytes [Medical Subject Headings], 0302 clinical medicine, Prospective Studies, lcsh:Science, Càncer, Cancer, 0303 health sciences, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Epidemiologic Factors::Age Factors [Medical Subject Headings], Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Epidemiologic Factors::Sex Factors [Medical Subject Headings], Genomics, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Specimen Handling [Medical Subject Headings], 3. Good health, SNP genotyping, 030220 oncology & carcinogenesis, Science & Technology - Other Topics, Medicine, Cellular Types, Genotyping, Anciano, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Habits::Smoking [Medical Subject Headings], Check Tags::Male [Medical Subject Headings], Specimen Handling, Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Hemolysis [Medical Subject Headings], 03 medical and health sciences, Cryobiology, AGE, Named Groups::Persons::Age Groups::Adult [Medical Subject Headings], Genetics, Genome-Wide Association Studies, QUALITY, Humans, Biology, Aged, Science & Technology, Blood Cells, lcsh:R, Computational Biology, DNA, Biotechnology, Check Tags::Female [Medical Subject Headings], Case-Control Studies, Leukocytes, Mononuclear, lcsh:Q, Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::DNA [Medical Subject Headings], Índice de Masa Corporal, lcsh:Medicine, Cancer risk, Nucleic Acids, Molecular Cell Biology, GENOME WIDE, RISK, 2. Zero hunger, Observer Variation, Multidisciplinary, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings], Smoking, Age Factors, Middle Aged, Haemolysis, Nutrition Surveys, CANCER, European Prospective Investigation into Cancer and Nutrition, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Research Design::Reproducibility of Results [Medical Subject Headings], Multidisciplinary Sciences, CELL COUNT, Genetic Epidemiology, SEX, Female, Research Article, Factores de Edad, Adult, VDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk genetikk: 714, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], Clinical Research Design, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Physical Examination::Body Constitution::Body Weights and Measures::Body Mass Index [Medical Subject Headings], VDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710::Medical genetics: 714, Hemolysis, Adult Age Factors Aged Body Mass Index Case-Control Studies DNA/blood/*isolation & purification Erythrocytes/chemistry Female Genotyping Techniques Hemolysis Humans Leukocytes, Sex Factors, Named Groups::Persons::Age Groups::Adult::Aged [Medical Subject Headings], Nutrició, 030304 developmental biology, Nutrition, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Genotyping Techniques [Medical Subject Headings], Population Biology, business.industry, Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear [Medical Subject Headings], Reproducibility of Results, DNA extraction, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Mononuclear/*chemistry Male Middle Aged Observer Variation Prospective Studies Reproducibility of Results Sex Factors Smoking Specimen Handling/*standards, business
Abstract: The European Prospective Investigation into Cancer and nutrition (EPIC) is a long-term, multi-centric prospective study in Europe investigating the relationships between cancer and nutrition. This study has served as a basis for a number of Genome-Wide Association Studies (GWAS) and other types of genetic analyses. Over a period of 5 years, 52,256 EPIC DNA samples have been extracted using an automated DNA extraction platform. Here we have evaluated the pre-analytical factors affecting DNA yield, including anthropometric, epidemiological and technical factors such as center of subject recruitment, age, gender, body-mass index, disease case or control status, tobacco consumption, number of aliquots of buffy coat used for DNA extraction, extraction machine or procedure, DNA quantification method, degree of haemolysis and variations in the timing of sample processing. We show that the largest significant variations in DNA yield were observed with degree of haemolysis and with center of subject recruitment. Age, gender, body-mass index, cancer case or control status and tobacco consumption also significantly impacted DNA yield. Feedback from laboratories which have analyzed DNA with different SNP genotyping technologies demonstrate that the vast majority of samples (approximately 88%) performed adequately in different types of assays. To our knowledge this study is the largest to date to evaluate the sources of pre-analytical variations in DNA extracted from peripheral leucocytes. The results provide a strong evidence-based rationale for standardized recommendations on blood collection and processing protocols for large-scale genetic studies. The study was funded by European Commission Research & Innovation DG project BBMRI (Biobanking and Biomolecular Resources Research Infrastructure, http://www.bbmri.eu), project number 212111 and by the Regular Budget of International Agency for Research on Cancer (IARC). DNA extraction data used in the study were generated as part of molecular epidemiological studies approved by the Steering Committee of the European Prospective Investigation into Cancer and Nutrition (EPIC, http://epic.iarc.fr). Detailed information about the funding of EPIC is available at http://epic.iarc.fr/funding.php. The funding agencies and organizations which provided funds for DNA extraction in specific EPIC studies were Imperial College London (ICL, BRCD study); Medical Research Council UK (MRC UK, EPHD study); European Community INTERACT project (through MRC Cambridge, UK, INT study, http://www.inter-act.eu); International Agency for Research on Cancer (IARC) and Imperial College London (ICL) (LUND study), EU FP6 Network of Excellence Environmental Cancer Risk, Nutrition and Individual Susceptibility (ECNIS, http:// www.ecnis.org); and Cancer Research UK (CRCUK) (LYMD study).
Published: 2012

9. Adiposity, hormone replacement therapy use and breast cancer risk by age and hormone receptor status: a large prospective cohort study

Author: Elio Riboli, Sabina Sieri, Sabina Rinaldi, Birgit Teucher, Petra H.M. Peeters, José Ramón Quirós, Rudolf Kaaks, Rebecca Ritte, María José Sánchez, Kim Overvad, Isabelle Romieu, Sanda Krum-Hansen, Franco Berrino, Naomi E. Allen, Françoise Clavel-Chapelon, Genevieve Buckland, Salvatore Panico, Anja Olsen, Afshan Siddiq, Heiner Boeing, David Cox, Eiliv Lund, Krasimira Aleksandrova, Malin Sund, Per Lenner, Rosario Tumino, Nicholas J. Wareham, Agnès Fournier, Annekatrin Lukanova, Eva Ardanaz, Carla H. van Gils, Pagona Lagiou, Inger T. Gram, Bas Bueno-de-Mesquita, Paolo Vineis, Sabine Rohrmann, Guy Fagherazzi, Thure Filskov Overvad, Antonia Trichopoulou, María Dolores Chirlaque, Pilar Amiano, Kay-Tee Khaw, Domenico Palli, Dimitrios Trichopoulos, Timothy J. Key, Anne Tjønneland, Laure Dossus, Ritte, R, Lukanova, A, Berrino, F, Dossus, L, Tj?nneland, A, Olsen, A, Overvad, Tf, Overvad, K, Clavel Chapelon, F, Fournier, A, Fagherazzi, G, Rohrmann, S, Teucher, B, Boeing, H, Aleksandrova, K, Trichopoulou, A, Lagiou, P, Trichopoulos, D, Palli, D, Sieri, S, Panico, Salvatore, Tumino, R, Vineis, P, Quir?s, Jr, Buckland, G, S?nchez, Mj, Amiano, P, Chirlaque, Md, Ardanaz, E, Sund, M, Lenner, P, Bueno de Mesquita, B, van Gils, Ch, Peeters, Ph, Krum Hansen, S, Gram, It, Lund, E, Khaw, Kt, Wareham, N, Allen, Ne, Key, Tj, Romieu, I, Rinaldi, S, Siddiq, A, Cox, D, Riboli, E, Kaaks, R., Khaw, Kay-Tee [0000-0002-8802-2903], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Division of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department of Preventive and Predictive Medicine, Fondazione IRCCS Instituto Nazionale dei Tumori, Cancer Epidemiology Institute, Danish Cancer Society, Department of Cardiology, Aarhus University [Aarhus], Department of Epidemiology, Aarhus University [Aarhus]-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Division of Cancer Epidemiology and Prevention, Institute of Social and Preventive Medicine, German Institute of Human Nutrition, Hellenic Health Foundation, WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene-Epidemiology and Medical Statistics-Athens Medical School, Harvard School of Public Health, Bureau of Epidemiologic Research, Academy of Athens, Molecular and Nutritional Epidemiology Unit, Scientific Institute of Tuscany-Cancer Research and Prevention Institute (ISPO), Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Department of Clinical and Experimental Medicine, Università degli studi di Napoli Federico II-Medical School, Cancer Registry and Histopathology Unit, Civile - M.P.Arezzo Hospital, Centre for Environment and Health, Imperial College London-School of public health, Human Genetics Foundation (HuGeF), Università degli studi di Torino (UNITO), Public Health and Health Planning Directorate, Universidad de Oviedo, Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology (ICO-IDIBELL)-Cancer Epidemiology Research Programme, Granada Cancer Registry, Andalusian School of Public Health [Granada], Consorcio de Investigación Biomédica en Red especializado en Epidemiología y Salud Pública (CIBERESP), Los Centros de Investigación Biomédica en Red (CIBER), Public Health Division of Gipuzkoa, Institute BIO Donostia-Health Department, Murcia Regional Health Authority, Navarra Public Health Institute, Leyre 15, Department of Surgery and Perioperative Sciences, Umea University Hospital, Department of Oncology and Radiation Sciences, Oncology, National Institute for Public Health and the Environment [Bilthoven] (RIVM), Department of Gastroenterology and Hepatology, University Medical Centre, Julius Center for Health Sciences and Primary Care, VU University Medical Center [Amsterdam], Department of Epidemiology and Biostatistics, Imperial College London-Faculty of Medicine-School of public health, Institute of Community Medicine, University of Tromsø (UiT), School of Clinical Medicine, University of Cambridge [UK] (CAM), Medical Research Council, Addenbrooke's Hospital-Epidemiology Unit, Cancer Epidemiology Unit, University of Oxford [Oxford], Unité d'épidémiologie nutritionnelle, Section Nutrition et Métabolisme-Centre Internationale de la recherche sur le cancer (CIRC), Department of Genomics of Common Disease, This work was (partly) supported by a grant from the German Research Foundation, Graduiertenkolleg 793: Epidemiology of communicable and chronic noncommunicable diseases and their interrelationships. The coordination of EPIC is financially supported by the European Commission Directorate General for Health and Consumer Protection (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by the Danish Cancer Society (Denmark), Ligue contre le Cancer, Mutuelle Générale de l'Education Nationale, and the Institut National de la Santé et de la Recherche Médicale (France), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and the Federal Ministry of Education and Research (Germany), the Hellenic Health Foundation, the Stavros Niarchos Foundation and the Hellenic Ministry of Health and Social Solidarity, the Italian Association for Research on Cancer (AIRC) and the National Research Council (Italy), the Dutch Ministry of Public Health, Welfare and Sport (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands (The Netherlands), ERC-2009-AdG 232997 and Nordforsk, the Nordic Centre of Excellence programme on Food, Nutrition and Health. (Norway), the Health Research Fund (FIS), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (number 6236) and Navarra, and ISCIII RTICC Red Temática de Investigación Cooperativa en Cáncer (R06/0020) (Spain), the Swedish Cancer Society, Swedish Scientific Council and the Regional Government of Skåne and Västerbotten (Sweden), Cancer Research UK, and the Medical Research Council, (United Kingdom)., [Ritte,R, Lukanova,A, Dossus,L, Rohrmann,S, Teucher,B, Kaaks,R] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Berrino,F] Department of Ritte et al. Breast Cancer Research Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Tjønneland,A, Olsen,A] Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark. [Overvad,TF] Department of Cardiology, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark. [Overvad,K] Department of Epidemiology, School of Public Health, Aarhus University, Aarhus, Denmark. [Clavel-Chapelon,F, Fournier,A, Fagherazzi,G] Centre for Research in Epidemiology and Population Health, INSERM, Institut Gustave Roussy, Villejuif, France. Paris South University, Villejuif, France. [Rohrmann,S] Division of Cancer Epidemiology and Prevention, Institute of Social and Preventive Medicine, Zurich, Switzerland. [Boeing,H, Aleksandrova,K] Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Nuthetal, Germany. [Trichopoulou,A, Lagiou,P] WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Goudi, Athens, Greece. [Trichopoulou, A] Hellenic Health Foundation, Athens, Greece. [Trichopoulos,D] Department of Epidemiology, Harvard School of Public Health, Boston, USA. Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. [Palli,D] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Scientific Institute of Tuscany, Florence, Italy. [Sieri,S] Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. [Panico,S] Department of Clinical and Experimental Medicine Medical School Federico II University, Naples, Italy. [Tumino, R] Cancer Registry and Histopathology Unit, ‘Civile M.P. Arezzo’ Hospital ASP 7, Ragusa, Italy. [Vineis,P, Riboli,E] Centre for Environment and Health School of Public Health, Imperial College London, London, UK. [Vineis,P] Human Genetics Foundation (HuGeF), Torino, Italy. [Quirós,JR] Public Health and Health Planning Directorate, Asturias, Spain. [Buckland,G] Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain. [Sánchez,MJ] Andalusian School of Public Health, Granada, Spain. [Sánchez,MJ, Amiano,P, Chirlaque,MD, Ardanaz,E] CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. [Amiano,P] Public Health Division of Gipuzkoa, Institute BIO Donostia, Health Department, Basque Region, Gipuzkoa, Spain. [Chirlaque,MD] Department of Epidemiology, Murcia Regional Health Authority, Murcia, Spain. [Ardanaz,E] Navarra Public Health Institute, Pamplona, Spain. [Sund,M] Department of Surgery and Perioperative Sciences, Umeå University Hospital, Umeå, Sweden. [Lenner,P] Department of Oncology and Radiation Sciences, Oncology, Umeå University Hospital, Umeå, Sweden. [Bueno-de-Mesquita,B] National Institute for Public Health and the Environment, Bilthoven, The Netherlands. Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands. [van Gils,CH, Peeters,PHM] Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands. [Peeters,PHM, Siddiq,A, Cox,D] Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Medicine, Imperial College, London, London, UK. [Krum-Hansen,S, Gram,IT, Lund,E] Institute of Community Medicine, University of Tromsø, Tromsø, Norway. [Khaw,KT] School of Clinical Medicine, University of Cambridge, The Old Schools, Trinity Lane, Cambridge, UK. [Wareham,N] Medical Research Council, Epidemiology Unit, Addenbrooke’s Hospital, Cambridge, UK. [Allen,NE, Key,TJ] Cancer Epidemiology Unit, University of Oxford, Oxford, UK. [Romieu,I, Rinaldi,S] Nutritional Epidemiology Group, Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC), Lyon, France. [Siddiq,A] Department of Genomics of Common Disease, School of Public Health, Imperial College London, London UK., University of Zurich, Kaaks, Rudolf, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Medical School-University of Naples Federico II = Università degli studi di Napoli Federico II, Università degli studi di Torino = University of Turin (UNITO), Universidad de Oviedo [Oviedo], University of Oxford, and BMC, Ed.
Subjects: Oncology, medicine.medical_treatment, body-mass index, Named Groups::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Body Mass Index, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], 0302 clinical medicine, Medicine, 1306 Cancer Research, Prospective Studies, Adiposity, estrogen-receptor, Aged, 80 and over, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Epidemiologic Factors::Age Factors [Medical Subject Headings], 3. Good health, Postmenopause, nutrition, Receptors, Estrogen, PREMENOPAUSAL WOMEN, Adiposidad, premenopausal omen, fat distribution, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk [Medical Subject Headings], 030220 oncology & carcinogenesis, Cohort, 2730 Oncology, Receptors, Progesterone, Factores de riesgo, Cohort study, medicine.medical_specialty, Named Groups::Persons::Age Groups::Adult::Young Adult [Medical Subject Headings], Estudios de cohortes, united-states, 03 medical and health sciences, Breast cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, Named Groups::Persons::Age Groups::Adult [Medical Subject Headings], Humans, Aged, Gynecology, Cancer och onkologi, Science & Technology, Proportional hazards model, weight, ONCOLOGY, medicine.disease, Check Tags::Female [Medical Subject Headings], Premenopause, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Cancer and Oncology, Surgery, Body mass index, Named Groups::Persons::Age Groups::Adult::Aged::Aged, 80 and over [Medical Subject Headings], postmenopausal women, Overweight, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Physical Examination::Body Constitution::Body Weights and Measures::Body Fat Distribution::Adiposity [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Cohort Studies, Risk Factors, 030212 general & internal medicine, Prospective cohort study, physical-activity, 2. Zero hunger, Medicine(all), Estrogen Replacement Therapy, Age Factors, Hormone replacement therapy (menopause), Estudios Prospectivos, Middle Aged, POSTMENOPAUSAL WOMEN, Neoplasias de la mama, NUTRITION, Female, medicine.symptom, Life Sciences & Biomedicine, Research Article, Factores de Edad, Adult, Risk, Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Climacteric::Menopause::Premenopause [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Drug Therapy::Hormone Replacement Therapy::Estrogen Replacement Therapy [Medical Subject Headings], Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::DNA-Binding Proteins::Receptors, Cytoplasmic and Nuclear::Receptors, Steroid::Receptors, Progesterone [Medical Subject Headings], UNITED-STATES, 610 Medicine & health, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Physical Examination::Body Constitution::Body Weights and Measures::Body Mass Index [Medical Subject Headings], [SDV.CAN]Life Sciences [q-bio]/Cancer, Breast Neoplasms, size, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::DNA-Binding Proteins::Receptors, Cytoplasmic and Nuclear::Receptors, Steroid::Receptors, Estrogen [Medical Subject Headings], Young Adult, Internal medicine, Named Groups::Persons::Age Groups::Adult::Aged [Medical Subject Headings], Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Receptores de Progesterona, business.industry, Kirurgi, FAT DISTRIBUTION, 10060 Epidemiology, Biostatistics and Prevention Institute (EBPI), Receptores Estrogénicos, BODY-MASS INDEX, ESTROGEN-RECEPTOR, PHYSICAL-ACTIVITY, SIZE, WEIGHT, business
Abstract: Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't; INTRODUCTION Associations of hormone-receptor positive breast cancer with excess adiposity are reasonably well characterized; however, uncertainty remains regarding the association of body mass index (BMI) with hormone-receptor negative malignancies, and possible interactions by hormone replacement therapy (HRT) use. METHODS Within the European EPIC cohort, Cox proportional hazards models were used to describe the relationship of BMI, waist and hip circumferences with risk of estrogen-receptor (ER) negative and progesterone-receptor (PR) negative (n = 1,021) and ER+PR+ (n = 3,586) breast tumors within five-year age bands. Among postmenopausal women, the joint effects of BMI and HRT use were analyzed. RESULTS For risk of ER-PR- tumors, there was no association of BMI across the age bands. However, when analyses were restricted to postmenopausal HRT never users, a positive risk association with BMI (third versus first tertile HR = 1.47 (1.01 to 2.15)) was observed. BMI was inversely associated with ER+PR+ tumors among women aged ≤49 years (per 5 kg/m2 increase, HR = 0.79 (95%CI 0.68 to 0.91)), and positively associated with risk among women ≥65 years (HR = 1.25 (1.16 to 1.34)). Adjusting for BMI, waist and hip circumferences showed no further associations with risks of breast cancer subtypes. Current use of HRT was significantly associated with an increased risk of receptor-negative (HRT current use compared to HRT never use HR: 1.30 (1.05 to 1.62)) and positive tumors (HR: 1.74 (1.56 to 1.95)), although this risk increase was weaker for ER-PR- disease (Phet = 0.035). The association of HRT was significantly stronger in the leaner women (BMI ≤22.5 kg/m2) than for more overweight women (BMI ≥25.9 kg/m2) for, both, ER-PR- (HR: 1.74 (1.15 to 2.63)) and ER+PR+ (HR: 2.33 (1.84 to 2.92)) breast cancer and was not restricted to any particular HRT regime. CONCLUSIONS An elevated BMI may be positively associated with risk of ER-PR- tumors among postmenopausal women who never used HRT. Furthermore, postmenopausal HRT users were at an increased risk of ER-PR- as well as ER+PR+ tumors, especially among leaner women. For hormone-receptor positive tumors, but not for hormone-receptor negative tumors, our study confirms an inverse association of risk with BMI among young women of premenopausal age. Our data provide evidence for a possible role of sex hormones in the etiology of hormone-receptor negative tumors. Yes
Published: 2012

10. Weight change in middle adulthood and risk of cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Author: Amanda J. Cross, Kristin Benjaminsen Borch, Renée T. Fortner, Vittorio Simeon, Paul Brennan, Guri Skeie, Elio Riboli, Rosario Tumino, Elisabete Weiderpass, Gianluca Severi, Carlotta Sacerdote, Kim Overvad, Manuela M. Bergmann, Isabel Drake, Sara Grioni, Panagiota Pagoni, Giovanna Masala, Pietro Ferrari, Heinz Freisling, Matthias B. Schulze, Maria Dolores Chirlaque, Pilar Amiano, Mattias Johansson, Ioanna Tzoulaki, Konstantinos K. Tsilidis, Timothy J. Key, J. Ramón Quirós, Eva Ardanaz, Antonio Agudo, Neil Murphy, Marie-Christine Boutron-Ruault, Christel Häggström, Sofia Christakoudi, Rudolf Kaaks, Merete Ellingjord-Dale, Sophia Harlid, Charlotta Rylander, Tanja Stocks, Anne Tjønneland, Fanny Artaud, Laure Dossus, Jytte Halkjær, Miguel Rodríguez-Barranco, Aurora Perez-Cornago, David C. Muller, Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Kræftens Bekæmpelse, DCS German Cancer Research Center, DKFZ Centre International de Recherche sur le Cancer, CIRC National Research Council, NRC Medical Research Council, MRC: MC_UU_00011/6, MR/M012190/1 Cancer Research UK, CRUK: C570/A16491, C8221/A19170 World Cancer Research Fund, WCRF European Commission, EC Institut National de la Santé et de la Recherche Médicale, Inserm Bundesministerium für Bildung und Forschung, BMBF Cancerfonden Ministerie van Volksgezondheid, Welzijn en Sport, VWS Ligue Contre le Cancer Vetenskapsrådet, VR Associazione Italiana per la Ricerca sul Cancro, AIRC Deutsche Krebshilfe Rijksinstituut voor Volksgezondheid en Milieu, RIVM Institut Gustave-Roussy Mutuelle Générale de l'Education Nationale, MGEN NIHR Imperial Biomedical Research Centre, BRC Fondation Gustave Roussy, The authors thank the National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands, for their contribution and ongoing support to the EPIC study. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Kr?ftens Bek?mpelse) (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle G?n?rale de l'Education Nationale, Institut National de la Sant? et de la Recherche M?dicale (INSERM) (France), German Cancer Aid (Deutsche Krebshilfe), German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), Federal Ministry of Education and Research (Bundesministerium f?r Bildung und Forschung, BMBF) (Germany), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), Health Research Fund (FIS-ISCIII), Regional Governments of Andaluc?a, Asturias, Basque Country, Murcia, Navarra, and the Catalan Institute of Oncology (Barcelona) (Spain), Swedish Cancer Society (Cancerfonden), Swedish Research Council (Vetenskapsr?det), County Councils of Sk?ne and V?sterbotten (Sweden), Cancer Research UK (C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (MR/M012190/1 to EPIC-Oxford) (United Kingdom). Panagiota Pagoni is funded by Medical Research Council (grant reference MC_UU_00011/6). Infrastructure support for the Department of Epidemiology and Biostatistics at Imperial College London (UK) was provided by the NIHR Imperial Biomedical Research Centre (BRC). The funders had no role in the design and conduct of the study, the collection, analysis and interpretation of the data, or the preparation, review and approval of the manuscript, or in the decision to submit the manuscript for publication., The authors thank the National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands, for their contribution and ongoing support to the EPIC study. The coordination of EPIC is financially supported by the European Commission (DG‐SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Kræftens Bekæmpelse) (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid (Deutsche Krebshilfe), German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF) (Germany), Associazione Italiana per la Ricerca sul Cancro‐AIRC‐Italy and National Research Council (Italy), Health Research Fund (FIS‐ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia, Navarra, and the Catalan Institute of Oncology (Barcelona) (Spain), Swedish Cancer Society (Cancerfonden), Swedish Research Council (Vetenskapsrådet), County Councils of Skåne and Västerbotten (Sweden), Cancer Research UK (C570/A16491 and C8221/A19170 to EPIC‐Oxford), Medical Research Council (MR/M012190/1 to EPIC‐Oxford) (United Kingdom). Panagiota Pagoni is funded by Medical Research Council (grant reference MC_UU_00011/6). Infrastructure support for the Department of Epidemiology and Biostatistics at Imperial College London (UK) was provided by the NIHR Imperial Biomedical Research Centre (BRC). The funders had no role in the design and conduct of the study, the collection, analysis and interpretation of the data, or the preparation, review and approval of the manuscript, or in the decision to submit the manuscript for publication., Associazione Italiana per la Ricerca sul Cancro, Bundesministerium für Bildung und Forschung, Cancer Research UK, Grant/Award Numbers: C570/A16491, C8221/A19170, Cancerfonden, Catalan Institute of Oncology Barcelona, Centre International de Recherche sur le Cancer, County Council of Skåne Sweden, County Council of Västerbotten Sweden, Deutsche Krebshilfe, Deutsches Krebsforschungszentrum, Directorate‐General for Health and Consumers, Dutch Ministry of Public Health, Welfare and Sports (VWS), Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), Health Research Fund (FIS‐ISCIII) Spain, Institut Gustave‐Roussy, Institut National de la Santé et de la Recherche Médicale, Kræftens Bekæmpelse, Ligue Contre le Cancer, LK Research Funds, Medical Research Council, Grant/Award Numbers: MC_UU_00011/6, MR/M012190/1, Mutuelle Générale de l'Education Nationale, National Research Council Italy, Netherlands Cancer Registry, Regional Government of Andalucía, Regional Government of Asturias, Regional Government of Basque Country, Regional Government of Murcia, Regional Government of Navarra, Statistics Netherlands, Vetenskapsrådet, World Cancer Research Fund (WCRF), Institut Gustave Roussy, International Agency for Research on Cancer, European Commission (DG‐SANCO) Funding information, Christakoudi, S., Pagoni, P., Ferrari, P., Cross, A. J., Tzoulaki, I., Muller, D. C., Weiderpass, E., Freisling, H., Murphy, N., Dossus, L., Turzanski Fortner, R., Agudo, A., Overvad, K., Perez-Cornago, A., Key, T. J., Brennan, P., Johansson, M., Tjonneland, A., Halkjaer, J., Boutron-Ruault, M. -C., Artaud, F., Severi, G., Kaaks, R., Schulze, M. B., Bergmann, M. M., Masala, G., Grioni, S., Simeon, V., Tumino, R., Sacerdote, C., Skeie, G., Rylander, C., Borch, K. B., Quiros, J. R., Rodriguez-Barranco, M., Chirlaque, M. -D., Ardanaz, E., Amiano, P., Drake, I., Stocks, T., Haggstrom, C., Harlid, S., Ellingjord-Dale, M., Riboli, E., Tsilidis, K. K., and Cancer Research UK
Subjects: Male, Cancer Research, middle adulthood, Overweight, Body Mass Index, Cohort Studies, 0302 clinical medicine, Weight loss, Risk Factors, Neoplasms, Prospective Studies, Correlation of Data, 2. Zero hunger, Ovarian Neoplasms, Obstetrics, Hazard ratio, PROLIFERATION, WOMEN, weight gain, Middle Aged, Kidney Neoplasms, 3. Good health, European Prospective Investigation into Cancer and Nutrition, BMI change, Europe, Oncology, 030220 oncology & carcinogenesis, ddc:540, Female, SQUAMOUS-CELL CARCINOMA, medicine.symptom, Life Sciences & Biomedicine, EXPRESSION, medicine.medical_specialty, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, LEPTIN, FATNESS, medicine, Humans, cancer, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, Obesity, Risk factor, Proportional Hazards Models, Cancer och onkologi, Science & Technology, business.industry, Weight change, Endometrial Neoplasms, BODY-MASS INDEX, ESTROGEN-RECEPTORS, Pancreatic Neoplasms, Nutrition Assessment, Cancer and Oncology, Institut für Ernährungswissenschaft, GAIN, weight loss, business, Weight gain, Body mass index
Abstract: International audience; Obesity is a risk factor for several major cancers. Associations of weight change in middle adulthood with cancer risk, however, are less clear. We examined the association of change in weight and body mass index (BMI) category during middle adulthood with 42 cancers, using multivariable Cox proportional hazards models in the European Prospective Investigation into Cancer and Nutrition cohort. Of 241 323 participants (31% men), 20% lost and 32% gained weight (>0.4 to 5.0 kg/year) during 6.9 years (average). During 8.0 years of follow-up after the second weight assessment, 20 960 incident cancers were ascertained. Independent of baseline BMI, weight gain (per one kg/year increment) was positively associated with cancer of the corpus uteri (hazard ratio [HR] = 1.14; 95% confidence interval: 1.05-1.23). Compared to stable weight (±0.4 kg/year), weight gain (>0.4 to 5.0 kg/year) was positively associated with cancers of the gallbladder and bile ducts (HR = 1.41; 1.01-1.96), postmenopausal breast (HR = 1.08; 1.00-1.16) and thyroid (HR = 1.40; 1.04-1.90). Compared to maintaining normal weight, maintaining overweight or obese BMI (World Health Organisation categories) was positively associated with most obesity-related cancers. Compared to maintaining the baseline BMI category, weight gain to a higher BMI category was positively associated with cancers of the postmenopausal breast (HR = 1.19; 1.06-1.33), ovary (HR = 1.40; 1.04-1.91), corpus uteri (HR = 1.42; 1.06-1.91), kidney (HR = 1.80; 1.20-2.68) and pancreas in men (HR = 1.81; 1.11-2.95). Losing weight to a lower BMI category, however, was inversely associated with cancers of the corpus uteri (HR = 0.40; 0.23-0.69) and colon (HR = 0.69; 0.52-0.92). Our findings support avoiding weight gain and encouraging weight loss in middle adulthood.
Published: 2021

11. Adherence to the World Cancer Research Fund/American Institute for Cancer Research cancer prevention recommendations and risk of in situ breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Author: Christina C. Dahm, Marc J. Gunter, Carlotta Sacerdote, Carmen Santiuste, Sabine Rohrmann, Merete Ellingjord-Dale, Cecilie Kyrø, Anika Hüsing, Renée T. Fortner, Eva Ardanaz, Antonia Trichopoulou, María Dolores López, Claudia Agnoli, Elisabete Weiderpass, Virginia Menéndez, Rudolf Kaaks, Signe Borgquist, Marina Kvaskoff, Patrick Arveux, Anne Tjønneland, Carlo La Vecchia, Helene Tilma Vistisen, Marije F. Bakker, Antonio Agudo, María José Sánchez, Agnès Fournier, Laure Dossus, Kay-Tee Khaw, Timothy J. Key, Guri Skeie, Eleni Peppa, Rosario Tumino, Elio Riboli, Salma Butt, Carla H. van Gils, Nena Karavasiloglou, Kostantinos K. Tsilidis, Tilman Kühn, Giovanna Masala, Inge Huybrechts, Matthias B. Schulze, Domenico Palli, Anna Karakatsani, Jenny Chang-Claude, Salvatore Panico, Apollo - University of Cambridge Repository, [Karavasiloglou,N, Rohrmann,S] Division of Chronic Disease Epidemiology, Institute for Epidemiology, Biostatistics and Prevention, University of Zurich, Zurich, Switzerland. [Karavasiloglou,N, Rohrmann,S] Cancer Registry Zurich and Zug, University Hospital Zurich, Zurich, Switzerland. [Karavasiloglou,N, Hüsing,A, Turzanski Fortner,R, Chang-Claude,J, Kaaks,R, Kühn,T] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Masala,G, Palli,D] Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network - ISPRO, Florence, Italy. [van Gils,CH, Bakker,MF] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands. [Huybrechts,I, Weiderpass,E, Dossus,L] International Agency for Research on Cancer, Lyon, France. [Weiderpas,E, Skeie,G] Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway. [Arveux,P, Fournier,A, Kvaskoff,M] CESP, Fac. de médecine - Univ. Paris-Sud, Fac. de médecine - UVSQ, INSERM, Université Paris-Saclay, Villejuif, France. [Arveux,P, Kvaskoff,M] Gustave Roussy, Villejuif, France. [Arveux,P] Breast and Gynaecologic Cancer Registry of Côte d’Or, Georges-François Leclerc Cancer Centre, UNICANCER, Dijon, France. [Tjønneland,A] Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. [Tjønneland,A, Kyrø,C] Danish Cancer Society Research Center, Copenhagen, Denmark. [Dahm,CC, Vistisen,HT] Department of Public Health, Aarhus University, Aarhus, Denmark. [Sánchez,MJ] Andalusian School of Public Health (EASP), Granada, Spain. [Sánchez,MJ] Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), Granada, Spain. [Sánchez,MJ, Chirlaque López,MD, Santiuste,C, Ardanaz,E] CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain. [Sánchez,MJ] Universidad de Granada, Granada, Spain. [Chirlaque López,MD, Santiuste,C] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. [Chirlaque López,MD] Department of Health and Social Sciences, Murcia University, Murcia, Spain. [Ardanaz,E] Navarra Public Health Institute, Pamplona, Spain. [Ardanaz,E] IdiSNA, Navarra Institute for Health Research, Pamplona, Spain. [Menéndez,V] Public Health Directorate, Asturias, Spain. [Agudo,A] Unit of Nutrition and Cancer, Catalan Institute of Oncology - ICO, Nutrition and Cancer Group, Bellvitge Biomedical Research Institute - IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain. [Trichopoulou,A, Karakatsani,A, La Vecchia,C, Peppa,E] Hellenic Health Foundation, Athens, Greece. [Karakatsani,A] 2nd Pulmonary Medicine Department, School of Medicine, 'ATTIKON' University Hospital, National and Kapodistrian University of Athens, Haidari, Greece. [La Vecchia,C] Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy. [Agnoli,C] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Panico,S] Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy. [Tumino,R] Cancer Registry and Histopathology Department, Azienda Sanitaria Provinciale (ASP), Ragusa, Italy. [Sacerdote,C] Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention (CPO), Turin, Italy. [Butt,ST] Department of Clinical Sciences, Lund University, Malmö, Sweden. [Butt,ST] Department of Surgery, Skåne University Hospital, Malmö, Sweden. [Borgquist,S] Department of Oncology, Aarhus University Hospital, Aarhus University, Aarhus, Denmark. [Borgquist,S] Division of Oncology and Pathology, Clinical Sciences, Lund University, Lund, Sweden. [Skeie,G] Nutritional Epidemiology Group, School of Food Science and Nutrition, University of Leeds, Leeds, UK. [Schulze,M] Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Nuthetal, Germany. [Key,T] Nuffield Department of Population Health, University of Oxford, Oxford, UK. [Khaw,KT] Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. [Tsilidis,KK, Ellingjord-Dale,M, Riboli,E] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Tsilidis,KK] Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece., The coordination of the European Prospective Investigation into Cancer and Nutrition (EPIC) is supported financially by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by the Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (France), German Cancer Aid, German Cancer Research Center (German Cancer Research Center), Federal Ministry of Education and Research (Federal Ministry of Education and Research), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum, and Federal Ministry of Education and Research (Germany), Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (Ministry of Health, Welfare and Sport), Netherlands Cancer Registry (Netherlands Cancer Registry), LK Research Funds, Dutch Prevention Funds, Dutch Zorg Onderzoek Nederland, World Cancer Research Fund, Statistics Netherlands (the Netherlands), Nordic Centre of Excellence Programme on Food, Nutrition and Health (Norway), Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), the Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO, Swedish Cancer Society, Swedish Research Council, and County Councils of Skåne and Västerbotten (Sweden), Cancer Research UK (14136 to EPIC-Norfolk, C570/A16491 and C8221/A19170 to EPIC-Oxford), and the Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (UK)., Tjønneland, Anne [0000-0003-4385-2097], Dahm, Christina C [0000-0003-0481-2893], Tumino, Rosario [0000-0003-2666-414X], and Borgquist, Signe [0000-0001-7938-8893]
Subjects: 0301 basic medicine, Male, Breastfeeding, lcsh:Medicine, Breast carcinoma in situ, GUIDELINES, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Cohort Studies, 0302 clinical medicine, Breast cancer, Risk Factors, Medicine, Prospective Studies, Prospective cohort study, 11 Medical and Health Sciences, Medicine(all), Geographical Locations::Geographic Locations::Americas::North America::United States [Medical Subject Headings], Hazard ratio, Academies and Institutes, Cohort, General Medicine, Middle Aged, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Lifestyle Score, Europe, POSTMENOPAUSAL WOMEN, 030220 oncology & carcinogenesis, Female, CONCORDANCE, Life Sciences & Biomedicine, PROJECT, In situ breast cancer, Cohort study, Research Article, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], Estudios de cohortes, RECREATIONAL PHYSICAL-ACTIVITY, Check Tags::Male [Medical Subject Headings], Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Data Collection::Nutrition Assessment [Medical Subject Headings], Breast Neoplasms, Estilo de vida, Càncer de mama, 03 medical and health sciences, Medicine, General & Internal, Medicina preventiva, DIETARY, General & Internal Medicine, Journal Article, Humans, VDP::Medisinske Fag: 700, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Carcinoma de mama in situ, Preventive medicine, 030109 nutrition & dietetics, Cancer prevention, Science & Technology, business.industry, Prevention, lcsh:R, Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], medicine.disease, Lifestyle, United States, VDP::Medical disciplines: 700, Nutrition Assessment, Health Care::Health Care Economics and Organizations::Organizations::Academies and Institutes [Medical Subject Headings], Check Tags::Female [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Cancer research, Life style, Geographical Locations::Geographic Locations::Europe [Medical Subject Headings], business
Abstract: Background Even though in situ breast cancer (BCIS) accounts for a large proportion of the breast cancers diagnosed, few studies have investigated potential risk factors for BCIS. Their results suggest that some established risk factors for invasive breast cancer have a similar impact on BCIS risk, but large population-based studies on lifestyle factors and BCIS risk are lacking. Thus, we investigated the association between lifestyle and BCIS risk within the European Prospective Investigation into Cancer and Nutrition cohort. Methods Lifestyle was operationalized by a score reflecting the adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations. The recommendations utilized in these analyses were the ones pertinent to healthy body weight, physical activity, consumption of plant-based foods, energy-dense foods, red and processed meat, and sugary drinks and alcohol, as well as the recommendation on breastfeeding. Cox proportional hazards regression was used to assess the association between lifestyle score and BCIS risk. The results were presented as hazard ratios (HR) and corresponding 95% confidence intervals (CI). Results After an overall median follow-up time of 14.9 years, 1277 BCIS cases were diagnosed. Greater adherence to the WCRF/AICR cancer prevention recommendations was not associated with BCIS risk (HR = 0.98, 95% CI 0.93–1.03; per one unit of increase; multivariable model). An inverse association between the lifestyle score and BCIS risk was observed in study centers, where participants were recruited mainly via mammographic screening and attended additional screening throughout follow-up (HR = 0.85, 95% CI 0.73–0.99), but not in the remaining ones (HR = 0.99, 95% CI 0.94–1.05). Conclusions While we did not observe an overall association between lifestyle and BCIS risk, our results indicate that lifestyle is associated with BCIS risk among women recruited via screening programs and with regular screening participation. This suggests that a true inverse association between lifestyle habits and BCIS risk in the overall cohort may have been masked by a lack of information on screening attendance. The potential inverse association between lifestyle and BCIS risk in our analyses is consistent with the inverse associations between lifestyle scores and breast cancer risk reported from previous studies.
Published: 2019

12. Prospective analysis of circulating metabolites and breast cancer in EPIC

Author: José María Huerta, Salvatore Panico, Antonia Trichopoulou, Joseph A. Rothwell, Sabina Sieri, Anja Olsen, Christina C. Dahm, Ruth C. Travis, Audrey Gicquiau, Pilar Amiano, Elisabete Weiderpass, N. Charlotte Onland-Moret, Antonio Agudo, Anna Karakatsani, Isabelle Romieu, Paolo Vineis, Mathilde His, Elio Riboli, Marc J. Gunter, Guri Skeie, Tilman Kühn, Augustin Scalbert, Carla H. van Gils, Georgia Martimianaki, Therese Haugdahl Nøst, Anne Tjønneland, Heiner Boeing, Laure Dossus, Pietro Ferrari, Julie A. Schmidt, Rosario Tumino, Konstantinos K. Tsilidis, David Achaintre, Torkjel M. Sandanger, Agnès Fournier, Sofia Christakoudi, María José Sánchez, Vivian Viallon, Renée T. Fortner, Kim Overvad, Giovanna Masala, Sabina Rinaldi, J. Ramón Quirós, Gianluca Severi, Eva Ardanaz, [His,M, Viallon,V, Dossus,L, Gicquiau,A, Achaintre,D, Scalbert,A, Ferrari,P, Weiderpass,E, Gunter,MJ, Rinaldi,S] International Agency for Research on Cancer, Lyon, France. [Romieu,I] Centre for Research on Population Health, National Institute of Public Health, Cuernavaca, Mexico. [Onland-Moret,NC, van Gils,CH] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands. [Dahm,CC, Overvad,K] Department of Public Health, Aarhus University, Aarhus, Denmark. [Overvad,K] Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark. [Olsen,A, Tjønneland,A] Danish Cancer Society Research Center, Copenhagen, Denmark. [Tjønneland,A] University of Copenhagen, Copenhagen, Denmark. [Fournier,A, Rothwell,JA, Severi,G] CESP, Université Paris-Sud, UVSQ, INSERM, Université Paris-Saclay, Villejuif, France. [Fournier,A, Severi,G] Gustave Roussy, Villejuif, France. [Kühn,T, Fortner,R] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Boeing,H] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany. [Trichopoulou,A, Karakatsani,A, Martimianaki,G] Hellenic Health Foundation, Athens, Greece. [Karakatsani,A] Pulmonary Medicine Department, School of Medicine, National and Kapodistrian University of Athens, 'ATTIKON' University Hospital, Haidari, Greece. [Masala,G] Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network – ISPRO, Florence, Italy. [Sieri,S] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy. [Tumino,R] Cancer Registry and Histopathology Department, 'M.P.Arezzo'Hospital, ASP Ragusa, Ragusa, Italy. [Vineis,P] Italian Institute for Genomic Medicine (IIGM), Turin, Italy. [Vineis,P] MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK. [Panico,S] Dipartimento di medicina clinica e chirurgia, Federico II University, Naples, Italy. [Nøst,TH, Sandanger,TM, Skeie,G] Department of Community Medicine, UiT the Arctic University of Norway, Tromso, Norway. [Skeie,G] Nutritional Epidemiology Group, School of Food Science and Nutrition, University of Leeds, Leeds, UK. [Quirós,JR] Public Health Directorate, Asturias, Spain. [Agudo,A] Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain. [Sánchez,MJ] Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs.GRANADA, Universidad de Granada, Granada, Spain. [Sánchez,MJ, Amiano,P, Huerta,JM, Ardanaz,E] CIBER Epidemiology and Public Health CIBERESP, Madrid, Spain. [Amiano,P] Public Health Division of Gipuzkoa, BioDonostia Research Institute, San Sebastian, Spain. [Huerta,JM] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. [Ardanaz,E] Navarra Public Health Institute, Pamplona, Spain. [Ardanaz,E] IdiSNA, Navarra Institute for Health Research, Pamplona, Spain. [Schmidt,JA, Travis,RC] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK. [Riboli,E, Tsilidis,KK, Christakoudi,S] Department of Epidemiology and Biostatistics, Imperial College London, St Mary’s Campus, Norfolk Place, London, UK. [Tsilidis,KK] Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece. [Christakoudi,S] MRC Centre for Transplantation, King’s College London, Great Maze Pond, London, SE1 9RT, UK, This work was funded by the French National Cancer Institute (grant number 2015-166). The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany), the Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), European Research Council (ERC-2009-AdG 232997), and Nordforsk, Nordic Centre of Excellence Programme on Food, Nutrition and Health (Norway), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236), Navarra, and the CERCA Program (Generalitat de Catalunya) (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), and Cancer Research UK (14136 to EPIC-Norfolk, and C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom).
Subjects: 0301 basic medicine, Oncology, lcsh:Medicine, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Probability::Risk::Risk Factors [Medical Subject Headings], Mass Spectrometry, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Cohort Studies, 0302 clinical medicine, Breast cancer, Information Science::Information Science::Data Collection::Vital Statistics::Morbidity::Incidence [Medical Subject Headings], Risk Factors, Estudios prospectivos, Prospective Studies, Prospective cohort study, 11 Medical and Health Sciences, Persons::Persons::Age Groups::Adult::Aged [Medical Subject Headings], education.field_of_study, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings], VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, Incidence, Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Biochemistry::Metabolomics [Medical Subject Headings], General Medicine, Metabolómica, Middle Aged, metabolomics, 3. Good health, Research Design, 030220 oncology & carcinogenesis, Cohort, Neoplasias de la mama, Female, Chemicals and Drugs::Biological Factors::Biological Markers::Biomarkers, Pharmacological [Medical Subject Headings], Cohort study, Research Article, prospective study, Adult, medicine.medical_specialty, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], Population, Breast Neoplasms, Càncer de mama, 03 medical and health sciences, breast cancer, Internal medicine, Cell Line, Tumor, General & Internal Medicine, medicine, Journal Article, Metabolomics, Humans, Prospective study, education, Persons::Persons::Age Groups::Adult [Medical Subject Headings], Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Aged, business.industry, lcsh:R, Case-control study, Cancer, Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Odds ratio, medicine.disease, 030104 developmental biology, Check Tags::Female [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Case-Control Studies, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Chemistry Techniques, Analytical::Mass Spectrometry [Medical Subject Headings], Biomarkers
Abstract: BackgroundMetabolomics is a promising molecular tool to identify novel etiologic pathways leading to cancer. Using a targeted approach, we prospectively investigated the associations between metabolite concentrations in plasma and breast cancer risk.MethodsA nested case-control study was established within the European Prospective Investigation into Cancer cohort, which included 1624 first primary incident invasive breast cancer cases (with known estrogen and progesterone receptor and HER2 status) and 1624 matched controls. Metabolites (n = 127, acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexose, sphingolipids) were measured by mass spectrometry in pre-diagnostic plasma samples and tested for associations with breast cancer incidence using multivariable conditional logistic regression.ResultsAmong women not using hormones at baseline (n = 2248), and after control for multiple tests, concentrations of arginine (odds ratio [OR] per SD = 0.79, 95% confidence interval [CI] = 0.70–0.90), asparagine (OR = 0.83 (0.74–0.92)), and phosphatidylcholines (PCs) ae C36:3 (OR = 0.83 (0.76–0.90)), aa C36:3 (OR = 0.84 (0.77–0.93)), ae C34:2 (OR = 0.85 (0.78–0.94)), ae C36:2 (OR = 0.85 (0.78–0.88)), and ae C38:2 (OR = 0.84 (0.76–0.93)) were inversely associated with breast cancer risk, while the acylcarnitine C2 (OR = 1.23 (1.11–1.35)) was positively associated with disease risk. In the overall population, C2 (OR = 1.15 (1.06–1.24)) and PC ae C36:3 (OR = 0.88 (0.82–0.95)) were associated with risk of breast cancer, and these relationships did not differ by breast cancer subtype, age at diagnosis, fasting status, menopausal status, or adiposity.ConclusionsThese findings point to potentially novel pathways and biomarkers of breast cancer development. Results warrant replication in other epidemiological studies.
Published: 2019

13. Development and validation of circulating CA125 prediction models in postmenopausal women

Author: J. Ramón Quirós, N. Charlotte Onland-Moret, Anna Karakatsani, Marina Kvaskoff, Raina N. Fichorova, Pilar Amiano, Eva Lundin, Louise Hansen, Kathryn L. Terry, Sara Grioni, Kay-Tee Khaw, Leila Lujan-Barroso, Amalia Mattiello, Renée T. Fortner, Agnès Fournier, Linda J. Titus, Rudolf Kaaks, Sandra Colorado-Yohar, Anne Tjønneland, Timothy J. Key, Marc J. Gunter, Aurelio Barricarte, Shelley S. Tworoger, Laure Dossus, Britton Trabert, Naoko Sasamoto, Inger T. Gram, David C. Muller, Hanna Sartor, Bernard Rosner, Allison F. Vitonis, Francesca Mancini, Eleni Peppa, Valentina Fiano, María José Sánchez, Heiner Boeing, Daniel W. Cramer, Ana Babic, Hidemi S. Yamamoto, Rosario Tumino, Nicolas Wentzensen, Domenico Palli, Annika Idahl, Elisabete Weiderpass, Antonia Trichopoulou, Elio Riboli, Sasamoto, Naoko [0000-0002-4526-2181], Tjønneland, Anne [0000-0003-4385-2097], Tumino, Rosario [0000-0003-2666-414X], Apollo - University of Cambridge Repository, [Sasamoto,N, Vitonis,AF, Cramer,DW, Terry,KL] Obstetrics and Gynecology Epidemiology Center, Brigham and Women’s Hospital and Harvard Medical School, 221 Longwood Avenue, Boston, MA, USA. [Babic,A] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. [Rosner,BA] Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA. [Fortner,RT, Kaaks,R] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Yamamoto,H, Fichorova,RN] Laboratory of Genital Tract Biology, Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women’s Hospital, Boston, MA, USA.[Titus,LJ] Departments of Epidemiology and Pediatrics, Geisel School of Medicine at Dartmouth and Norris Cotton Cancer Center, Hanover, NH, USA. [Tjønneland,A, Hansen,L] Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark. [Tjønneland,A] Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. [Kvaskoff,M, Fournier,A, Mancini,FR] CESP, Fac. de médecine - Univ. Paris-Sud, Fac. de médecine - UVSQ, INSERM, Université Paris-Saclay, Villejuif, France. [Kvaskoff,M, Mancini,FR] Gustave Roussy, Villejuif, France. [Boeing,H] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany. [Trichopoulou,A, Peppa,E, Karakatsani,A] Hellenic Health Foundation, Athens, Greece. [Trichopoulou,A] WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Dept. of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece. [Karakatsani,A] 2nd Pulmonary Medicine Department, School of Medicine, 'ATTIKON' University Hospital, National and Kapodistrian University of Athens, Haidari, Greece. [Palli,D] Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network - ISPRO, Florence, Italy. [Grioni,S] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milano, Italy. [Mattiello,A] Dipartimento Di Medicina Clinica E Chirurgia, Federico II University, Naples, Italy. [Tumino,R] Cancer Registry and Histopathology Department, 'Civic - M.P. Arezzo'Hospital, ASP, Ragusa, Italy. [Fiano,V] Unit of Cancer Epidemiology– CeRMS, Department of Medical Sciences, University of Turin, Turin, Italy. [Onland-Moret,NC] Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands. [Weiderpass,E, Gunter,M, Dossus,L] International Agency for Research on Cancer, Lyon, France. [Gram,IT] Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway. [Quirós,JR] Public Health Directorate, Asturias, Spain. [Lujan-Barroso,L] Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO-IDIBELL), L’ Hospitalet de Llobregat, Barcelona, Spain. [Sánchez,MJ] Andalusian School of Public Health (EASP), Granada, Spain. [Sánchez,MJ] Instituto de Investigación Biosanitaria de Granada (ibs. GRANADA). Universidad de Granada, Granada, Spain. [Sánchez,MJ, Colorado-Yohar,S, Barricarte,A, Amiano,P] CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain. [Colorado-Yohar,S] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. [Colorado-Yohar,S] Research Group on Demography and Health, National Faculty of Public Health, University of Antioquia, Medellín, Colombia. [Barricarte,A] Navarra Public Health Institute, Navarra Institute for Health Research (IdiSNA), Pamplona, Spain. [Amiano,P] Public Health Division of Gipuzkoa, BioDonostia Research Institute, San Sebastian, Spain. [Idahl,A] Department of Clinical Sciences, Obstetrics and Gynecology, Umeå University, Umeå, Sweden. [Lundin,E] Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden. [Sartor,H] Department of Medical Imaging and Physiology, Skåne University Hospital, Lund, Sweden. [Sartor,H] Department of Translational Medicine, Lund University, Lund, Sweden. [Khaw,KT] Cancer Epidemiology Unit, University of Cambridge, Cambridge, UK. [Key,TJ] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK. [Muller,D, Riboli,E] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Trabert,B, Wentzensen,N] Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Washington, D.C, USA. [Tworoger,SS] Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida, USA. [Tworoger,SS, Terry,KL] Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA., Research reported in this publication was supported by U.S. National Institutes of Health under the following award numbers: R01 CA193965 (to K.L. Terry), R01 CA 158119 and R35 CA197605 (to D.W. Cramer), P01 CA087969 (to S.S. Tworoger), UM1 CA186107, R01 CA49449, UM1 CA176726, R01 CA67262, and supported in part by the intramural research program of the U.S. National Cancer Institute, National Institutes of Health, Department of Health and Human Services. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany), the Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway), Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten, The Cancer Research Foundation of Northern Sweden (Sweden), Cancer Research UK (14136 to EPIC-Norfolk, and C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom).
Subjects: Antígeno Ca-125, Oncology, endocrine system diseases, medicine.medical_treatment, Càncer d'ovari, Ovarian neoplasms, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Theoretical [Medical Subject Headings], 0302 clinical medicine, Neoplasms, PROSTATE, 030212 general & internal medicine, CA-125, Early Detection of Cancer, Persons::Persons::Age Groups::Adult::Aged [Medical Subject Headings], 2. Zero hunger, RISK, Reproductive Biology, Biochemical markers, Obstetrics and Gynecology, Early detection, Diseases::Neoplasms [Medical Subject Headings], Middle Aged, Early diagnosis, female genital diseases and pregnancy complications, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Menopause, Postmenopause, Posmenopausia, 030220 oncology & carcinogenesis, Marcadors bioquímics, Biomarker (medicine), Female, Postmenopausal, Life Sciences & Biomedicine, Menopausa, medicine.medical_specialty, Neoplasias ováricas, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Early Diagnosis::Early Detection of Cancer [Medical Subject Headings], BIOMARKERS, CA125, Ovarian cancer, Prediction model, Reproduktionsmedicin och gynekologi, lcsh:Gynecology and obstetrics, Chemicals and Drugs::Biological Factors::Antigens::Antigens, Neoplasm::Antigens, Tumor-Associated, Carbohydrate::CA-125 Antigen [Medical Subject Headings], OVARIAN-CANCER, 03 medical and health sciences, Diagnóstico precoz, Internal medicine, Obstetrics, Gynecology and Reproductive Medicine, medicine, Journal Article, Humans, VDP::Medisinske Fag: 700, Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Reproductive Physiological Processes::Sexual Development::Climacteric::Menopause::Postmenopause [Medical Subject Headings], lcsh:RG1-991, Aged, Hysterectomy, Science & Technology, business.industry, Research, Case-control study, CANCER SCREENING TRIAL, Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Stepwise regression, Models, Theoretical, medicine.disease, VDP::Medical disciplines: 700, Detección precoz del cáncer, Check Tags::Female [Medical Subject Headings], CA-125 Antigen, Hormone therapy, business, Body mass index, LUNG
Abstract: Background Cancer Antigen 125 (CA125) is currently the best available ovarian cancer screening biomarker. However, CA125 has been limited by low sensitivity and specificity in part due to normal variation between individuals. Personal characteristics that influence CA125 could be used to improve its performance as screening biomarker. Methods We developed and validated linear and dichotomous (≥35 U/mL) circulating CA125 prediction models in postmenopausal women without ovarian cancer who participated in one of five large population-based studies: Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO, n = 26,981), European Prospective Investigation into Cancer and Nutrition (EPIC, n = 861), the Nurses’ Health Studies (NHS/NHSII, n = 81), and the New England Case Control Study (NEC, n = 923). The prediction models were developed using stepwise regression in PLCO and validated in EPIC, NHS/NHSII and NEC. Result The linear CA125 prediction model, which included age, race, body mass index (BMI), smoking status and duration, parity, hysterectomy, age at menopause, and duration of hormone therapy (HT), explained 5% of the total variance of CA125. The correlation between measured and predicted CA125 was comparable in PLCO testing dataset (r = 0.18) and external validation datasets (r = 0.14). The dichotomous CA125 prediction model included age, race, BMI, smoking status and duration, hysterectomy, time since menopause, and duration of HT with AUC of 0.64 in PLCO and 0.80 in validation dataset. Conclusions The linear prediction model explained a small portion of the total variability of CA125, suggesting the need to identify novel predictors of CA125. The dichotomous prediction model showed moderate discriminatory performance which validated well in independent dataset. Our dichotomous model could be valuable in identifying healthy women who may have elevated CA125 levels, which may contribute to reducing false positive tests using CA125 as screening biomarker.
Published: 2019

14. Osteoprotegerin and breast cancer risk by hormone receptor subtype: A nested case-control study in the EPIC cohort

Author: Miren Dorronsoro, Marc J. Gunter, Mathilde His, Helena Schock, Sabina Sieri, Maria Dolores Chirlaque, Aurélie Affret, Rudolf Kaaks, Elisabete Weiderpass, H. Bas Bueno-de-Mesquita, Philippos Orfanos, Melissa A. Merritt, Anne Tjønneland, Domenico Palli, J. Ramón Quirós, María José Sánchez, Theron Johnson, Danja Sarink, Eva Ardanaz, Antonio Agudo, Renée T. Fortner, Laure Dossus, Timothy J. Key, Kim Overvad, Rosario Tumino, Androniki Naska, Petra H.M. Peeters, Heiner Boeing, Amalia Mattiello, Anja Olsen, Sabina Rinaldi, Eiliv Lund, Antonia Trichopoulou, Carla H. van Gils, Marie-Christine Boutron-Ruault, Kay-Tee Khaw, Elio Riboli, Fulvio Ricceri, Khaw, Kay-Tee [0000-0002-8802-2903], Apollo - University of Cambridge Repository, University Medical Center Utrecht, Imperial College Trust, [Fortner,RT, Sarink,D, Schock,H, Johnson,T, Kaaks,R] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Tjønneland,A, Olsen,A] Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark. [Overvad,K] Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark. [Affret,A, His,M, Boutron-Ruault,MC] Université Paris-Saclay, Université Paris-Sud, UVSQ, CESP, INSERM, Villejuif, France. [Affret,A, Boutron-Ruault,MC] Villejuif, France. [Boeing,H] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany. [Trichopoulou,A, Naska,A, Orfanos,P] Hellenic Health Foundation, Athens, Greece. [Trichopoulou,A, Orfanos,P] WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. [Palli,D] Cancer Risk Factors and Life-Style Epidemiology Unit, Cancer Research and Prevention Institute - ISPO, Florence, Italy. [Sieri,S] Epidemiology and Prevention Unit, Department of Preventive & Predictive Medicine Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Mattiello,A] Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy. [Tumino,R] Cancer Registry and Histopathology Unit, 'Civic - M.p.Arezzo' Hospital, ASP Ragusa, Italy. [Ricceri,F] Unit of Epidemiology, Regional Health Service ASL TO3, Grugliasco (TO), Italy. [Ricceri,F] Unit of Cancer Epidemiology, Department of Medical Sciences, University of Turin, Turin, Italy. [Bueno-de-Mesquita,HB] Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. [Bueno-de-Mesquita,HB, Merritt,MA, Riboli,E] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Bueno-de-Mesquita,HB] Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. [Peeters,PH, Van Gils,CH] Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands. [Peeters,PH] MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, UK. [Weiderpass,E, Lund,E] Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway. [Weiderpass,E] Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway. [Weiderpass,E] Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. [Weiderpass,E] Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland. [Quirós,JR] Public Health Directorate, Asturias, Spain. [Agudo,A] Unit of Nutrition and Cancer. Cancer Epidemiology Research Program. Catalan Institute of Oncology-IDIBELL. L'Hospitalet de Llobregat, Barcelona, Spain. [Sánchez,MJ] Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria ibs. GRANADA. Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain. [Sánchez,MJ, Chirlaque,MD, Ardanaz,E] CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. [Chirlaque,MD] Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia, Spain. [Chirlaque,MD] Department of Health and Social Sciences, Universidad de Murcia, Murcia, Spain. [Ardanaz,E] Navarra Public Health Institute, Pamplona, Spain. [Ardanaz,E] IdiSNA, Navarra Institute for Health Research, Pamplona, Spain. [Dorronsoro,M] Public Health Direction and Biodonostia Research Institute CIBERESP, Basque Regional Health Department, San Sebastian, Spain. [Key,T] Nuffield Department of Population Health, University of Oxford, Oxford, UK. [Khaw,KT] Cancer Epidemiology Unit, University of Cambridge, Cambridge, UK. [Rinaldi,S, Dossus,L, Gunter,M] International Agency for Research on Cancer, Lyon, France., This project was funded by research grant 111454 from the Deutsche Kresbshilfe. RT Fortner was supported by a Marie Curie International Incoming Fellowship of the European Commission’s Seventh Framework Programme (MC-IIF-623984). The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by the Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, and Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum, and Federal Ministry of Education and Research (Germany), the Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and the National Research Council (Italy), the Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands (The Netherlands), ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway), Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia, and Navarra, and ISCIII RETIC (RD06/0020) (Spain), the Swedish Cancer Society, Swedish Research Council, and County Councils of Skåne and Västerbotten (Sweden), and Cancer Research UK (14136 to EPIC-Norfolk, and C570/A16491 and C8221/A19170 to EPIC-Oxford), and the Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (UK).
Subjects: 0301 basic medicine, Oncology, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Transcription Factors::Receptors, Cytoplasmic and Nuclear::Receptors, Steroid::Receptors, Progesterone [Medical Subject Headings], Estrogen receptor, Progesterone receptor, Cohort Studies, 0302 clinical medicine, Breast cancer, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Immunologic::Receptors, Cytokine::Receptors, Tumor Necrosis Factor::Receptor Activator of Nuclear Factor-kappa B [Medical Subject Headings], Risk Factors, Prospective Studies, Prospective cohort study, Medicine(all), Osteoprotegerina, biology, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, 11 Medical And Health Sciences, General Medicine, Middle Aged, Necrosi, 3. Good health, European Prospective Investigation into Cancer and Nutrition, RANK axis, RANKL, 030220 oncology & carcinogenesis, Neoplasias de la mama, Female, Research Article, musculoskeletal diseases, medicine.medical_specialty, Receptores estrogénicos, Health Care::Environment and Public Health::Public Health::Epidemiologic Factors::Causality::Risk Factors [Medical Subject Headings], Breast Neoplasms, Receptores de progesterona, Receptores de hormonas, Hormone receptor, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::DNA-Binding Proteins::Receptors, Cytoplasmic and Nuclear::Receptors, Steroid::Receptors, Estrogen [Medical Subject Headings], Càncer de mama, Health Care::Environment and Public Health::Public Health::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings], Necrosis, 03 medical and health sciences, Osteoprotegerin, General & Internal Medicine, Internal medicine, Journal Article, medicine, Humans, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], business.industry, Case-control study, medicine.disease, Health Care::Environment and Public Health::Public Health::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Prospective Studies [Medical Subject Headings], 030104 developmental biology, Endocrinology, Case-Control Studies, Nested case-control study, Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Climacteric::Menopause::Postmenopause [Medical Subject Headings], biology.protein, Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, Immunologic::Receptors, Cytokine::Receptors, Tumor Necrosis Factor::Tumor Necrosis Factor Decoy Receptors::Osteoprotegerin [Medical Subject Headings], VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business
Abstract: All Author: Renée T. Fortner, Danja Sarink, Helena Schock, Theron Johnson, Anne Tjønneland, Anja Olsen, Kim Overvad, Aurélie Affret, Mathilde His, Marie-Christine Boutron-Ruault, Heiner Boeing, Antonia Trichopoulou, Androniki Naska, Philippos Orfanos, Domenico Palli, Sabina Sieri, Amalia Mattiello, Rosario Tumino, Fulvio Ricceri, H. Bas Bueno-de-Mesquita, Petra H. M. Peeters, Carla H. Van Gils, Elisabete Weiderpass, Eiliv Lund, J. Ramón Quirós, Antonio Agudo, Maria-José Sánchez, María-Dolores Chirlaque, Eva Ardanaz, Miren Dorronsoro, Tim Key, Kay-Tee Khaw, Sabina Rinaldi, Laure Dossus, Marc Gunter, Melissa A. Merritt, Elio Riboli and Rudolf Kaaks, Background: Circulating osteoprotegerin (OPG), a member of the receptor activator of nuclear factor kappa-B (RANK) axis, may influence breast cancer risk via its role as the decoy receptor for both the RANK ligand (RANKL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Circulating OPG and breast cancer risk has been examined in only one prior study. Methods: A case-control study was nested in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 2008 incident invasive breast cancer cases (estrogen receptor (ER)+, n = 1622; ER–, n = 386), matched 1:1 to controls, were included in the analysis. Women were predominantly postmenopausal at blood collection (77%); postmenopausal women included users and non-users of postmenopausal hormone therapy (HT). Serum OPG was quantified with an electrochemiluminescence assay. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. Results: The associations between OPG and ER+ and ER– breast cancer differed significantly. Higher concentrations of OPG were associated with increased risk of ER– breast cancer (top vs. bottom tertile RR = 1.93 [95% CI 1.24–3.02]; ptrend = 0.03). We observed a suggestive inverse association for ER+ disease overall and among women premenopausal at blood collection. Results for ER– disease did not differ by menopausal status at blood collection (phet = 0.97), and we observed no heterogeneity by HT use at blood collection (phet ≥ 0.43) or age at breast cancer diagnosis (phet ≥ 0.30). Conclusions: This study provides the first prospective data on OPG and breast cancer risk by hormone receptor subtype. High circulating OPG may represent a novel risk factor for ER– breast cancer., This project was funded by research grant 111454 from the Deutsche Kresbshilfe. RT Fortner was supported by a Marie Curie International Incoming Fellowship of the European Commission’s Seventh Framework Programme (MC-IIF-623984). The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by the Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, and Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum, and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and the National Research Council (Italy); the Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands (The Netherlands); ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia, and Navarra, and ISCIII RETIC (RD06/0020) (Spain); the Swedish Cancer Society, Swedish Research Council, and County Councils of Skåne and Västerbotten (Sweden); and Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), and the Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (UK).
Published: 2017

15. Circulating prolactin and breast cancer risk among pre- and postmenopausal women in the EPIC cohort

Author: Antonia Trichopoulou, M-J Sanchez, Laura Baglietto, Elisabete Weiderpass, Virginia Menéndez, Evelyn M. Monninkhof, Anne Tjønneland, A. Olsen, Laure Dossus, V. Pala, R. Tumino, Marc J. Gunter, Salvatore Panico, Kim Overvad, Disorn Sookthai, F. Clavel-Chapelon, Timothy J. Key, Pagona Lagiou, Rudolf Kaaks, Pilar Amiano, Charlotte Onland-Moret, Ruth C. Travis, Theron Johnson, Stefano Rosso, Kay-Tee Khaw, Anne Andersson, Dimitrios Trichopoulos, Eva Ardanaz, Antonio Agudo, Isabelle Romieu, Elio Riboli, Kaja Tikk, H. Boeing, Malin Sund, J. M. Huerta Castano, Hendrik B. Bueno-de-Mesquita, Domenico Palli, S. Rinaldi, Tikk, K, Sookthai, D, Johnson, T, Rinaldi, S, Romieu, I, Tj?nneland, A, Olsen, A, Overvad, K, Clavel Chapelon, F, Baglietto, L, Boeing, H, Trichopoulou, A, Lagiou, P, Trichopoulos, D, Palli, D, Pala, V, Tumino, R, Rosso, S, Panico, Salvatore, Agudo, A, Men?ndez, V, S?nchez, Mj, Amiano, P, Huerta Casta?o, Jm, Ardanaz, E, Bueno de Mesquita, Hb, Monninkhof, E, Onland Moret, C, Andersson, A, Sund, M, Weiderpass, E, Khaw, Kt, Key, Tj, Travis, Rc, Gunter, Mj, Riboli, E, Dossus, L, and Kaaks, R.
Subjects: Oncology, medicine.medical_specialty, medicine.medical_treatment, Prolactin levels, Breast Neoplasms, Progesterone receptor, Cohort Studies, Breast cancer, Risk Factors, Internal medicine, Estrogen receptor, Humans, Medicine, Prospective cohort study, Gynecology, business.industry, Case-control study, Hormone replacement therapy (menopause), Hematology, Prospective cohort, medicine.disease, Prolactin, Postmenopause, Menopause, Hormone replacement therapy, Case-Control Studies, Female, Premenopause, Cohort, business, Cohort study
Abstract: BACKGROUND: Experimental and epidemiological evidence suggests that prolactin might play a role in the etiology of breast cancer. We analyzed the relationship of prediagnostic circulating prolactin levels with the risk of breast cancer by menopausal status, use of postmenopausal hormone replacement therapy (HRT) at blood donation, and by estrogen and progesterone receptor status of the breast tumors. PATIENTS AND METHODS: Conditional logistic regression was used to analyze the data from a case-control study nested within the prospective European EPIC cohort, including 2250 invasive breast cancer and their matched control subjects. RESULTS: Statistically significant heterogeneity in the association of prolactin levels with breast cancer risk between women who were either pre- or postmenopausal at the time of blood donation was observed (Phet = 0.04). Higher serum levels of prolactin were associated with significant increase in the risk of breast cancer among postmenopausal women [odds ratio (OR)Q4-Q1 = 1.29 (95% confidence interval, CI, 1.05-1.58), Ptrend = 0.09]; however, this increase in risk seemed to be confined to women who used postmenopausal HRT at blood donation [ORQ4-Q1 = 1.45 (95% CI 1.08-1.95), Ptrend = 0.01], whereas no statistically significant association was found for the non-users of HRT [ORQ4-Q1 = 1.11 (95%CI 0.83-1.49), Ptrend = 0.80] (Phet = 0.08). Among premenopausal women, a statistically non-significant inverse association was observed [ORQ4-Q1 = 0.70 (95% CI 0.48-1.03), Ptrend = 0.16]. There was no heterogeneity in the prolactin-breast cancer association by hormone receptor status of the tumor. CONCLUSION: Our study indicates that higher circulating levels of prolactin among the postmenopausal HRT users at baseline may be associated with increased breast cancer risk.
Published: 2014

16. Anthropometric characteristics and risk of lymphoid and myeloid leukemia in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Author: Miren Dorronsoro, Martine M. Ros, Ruth C. Travis, Fatemeh Saberi Hosnijeh, Petra H.M. Peeters, Eva Ardanaz, Giovanna Tagliabue, Françoise Clavel-Chapelon, A Lukanova, José María Huerta, Pagona Lagiou, Dorthe Johansen, H. Bas Bueno-de-Mesquita, Roel Vermeulen, Valentina Gallo, Michael Katsoulis, Signe Borgquist, Guy Fagherazzi, Isabelle Romieu, Elio Riboli, Rudolf Kaaks, María José Sánchez, Jytte Halkjær, Anne Tjønneland, Laure Dossus, Salvatore Panico, Timothy J. Key, Catalina Bonet, Paolo Vineis, Antonia Trichopoulou, Saberi Hosnijeh, F, Romieu, I, Gallo, V, Riboli, E, Tj?nneland, A, Halkj?r, J, Fagherazzi, G, Clavel Chapelon, F, Dossus, L, Lukanova, A, Kaaks, R, Trichopoulou, A, Lagiou, P, Katsoulis, M, Panico, Salvatore, Tagliabue, G, Bonet, C, Dorronsoro, M, Huerta, Jm, Ardanaz, E, S?nchez, Mj, Johansen, D, Borgquist, S, Peeters, P, Bueno de Mesquita, Hb, Ros, Mm, Travis, Rc, Key, Tj, Vineis, P, and Vermeulen, R.
Subjects: Male, Oncology, Cancer Research, medicine.medical_specialty, Myeloid, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, hemic and lymphatic diseases, Internal medicine, medicine, Humans, Obesity, Prospective Studies, 030212 general & internal medicine, Risk factor, Abdominal obesity, Molecular epidemiology Aetiology, screening and detection [NCEBP 1], 2. Zero hunger, business.industry, Myeloid leukemia, Middle Aged, medicine.disease, Leukemia, Lymphoid, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, Leukemia, medicine.anatomical_structure, Leukemia, Myeloid, 030220 oncology & carcinogenesis, Immunology, Female, medicine.symptom, business, Body mass index, Lymphoid leukemia
Abstract: Item does not contain fulltext PURPOSE: Overweight and obesity have been suggested as a risk factor for leukemia. Impaired immune function associated with obesity, increased insulin-like growth factor-I activity and stimulating effects of leptin suggest a possible biological link between anthropometric measures and leukemia. However, evidence from epidemiological studies has been inconsistent. We examined the potential association between prospective measurements of body size and risk of leukemia among participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). METHODS: During follow-up (mean = 11.52 years, standard deviation = 2.63), 671 leukemia (lymphoid leukemia = 50.1 %, myeloid leukemia = 43.2 %) cases were identified. Anthropometric measures including weight, height, body mass index (BMI), waist circumference (WC), hip circumference, and waist-to-hip ratio (WHR) were measured. Cox proportional hazard models were used to explore the association between anthropometric measures and risk of leukemia. RESULTS: No associations were observed between anthropometric measures and total leukemia, and lymphoid leukemia. Risk of myeloid leukemia significantly increased for higher categories of BMI and WC among women. Analyses by subtype of myeloid leukemia showed an increased risk of acute myeloid leukemia (AML) for higher categories of WHR among women. This association seemed to be reversed for chronic myeloid leukemia. No association between anthropometric measures and myeloid leukemia were observed among men except an increased risk of AML with height. CONCLUSION: The study showed no associations between anthropometric measures and total leukemia, and lymphoid leukemia among men and women. A possible association between BMI as general obesity and WC as abdominal obesity and increased risk of myeloid leukemia among women were observed.
Published: 2013

17. Obesity, inflammatory markers, and endometrial cancer risk: a prospective case-control study

Author: Jakob Stegger, Petra H.M. Peeters, Kay-Tee Khaw, Jone M. Altzibar, Kim Overvad, Nicholas J. Wareham, Anne Tjønneland, Göran Hallmans, María José Sánchez, Timothy J. Key, María Dolores Chirlaque, Carlotta Sacerdote, Sabina Rinaldi, Vassiliki Benetou, Fränzel J.B. Van Duijnhoven, N. Charlotte Onland-Moret, Sabine Rohrmann, Salvatore Panico, Laure Dossus, Eva Lundin, Maria Luisa Redondo, Madlen Schütze, Susen Becker, Birgit Teucher, Anja Olsen, Aida Jimenez-Corona, Rudolf Kaaks, Heiner Boeing, Dora Romaguera, Rosario Tumino, H. Bas Bueno-de-Mesquita, Franco Berrino, Teresa Norat, Naomi E. Allen, Domenico Palli, Nathalie Chabbert-Buffet, Eva Ardanaz, Pierre Hainaut, Nadia Slimani, Antonia Trichopoulou, Elio Riboli, Annekatrin Lukanova, Pagona Lagiou, Noémie Travier, Françoise Clavel-Chapelon, Dossus, L, Rinaldi, S, Becker, S, Lukanova, A, Tjonneland, A, Olsen, A, Stegger, J, Overvad, K, Chabbert Buffet, N, Jimenez Corona, A, Clavel Chapelon, F, Rohrmann, S, Teucher, B, Boeing, H, Schütze, M, Trichopoulou, A, Benetou, V, Lagiou, P, Palli, D, Berrino, F, Panico, Salvatore, Tumino, R, Sacerdote, C, Redondo, Ml, Travier, N, Sanchez, Mj, Altzibar, Jm, Chirlaque, Md, Ardanaz, E, Bueno de Mesquita, Hb, van Duijnhoven, Fj, Onland Moret, Nc, Peeters, Ph, Hallmans, G, Lundin, E, Khaw, Kt, Wareham, N, Allen, N, Key, Tj, Slimani, N, Hainaut, P, Romaguera, D, Norat, T, Riboli, E, and Kaaks, R.
Subjects: Risk, Cancer Research, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Gastroenterology, Body Mass Index, Endocrinology, Risk Factors, Internal medicine, Odds Ratio, medicine, Humans, Obesity, Prospective Studies, Risk factor, Prospective cohort study, Aged, Immunoassay, Inflammation, biology, Interleukin-6, business.industry, Endometrial cancer, C-reactive protein, Age Factors, Regular Papers, Case-control study, Odds ratio, Middle Aged, medicine.disease, Endometrial Neoplasms, European Prospective Investigation into Cancer and Nutrition, Interleukin 1 Receptor Antagonist Protein, C-Reactive Protein, Logistic Models, Oncology, Quartile, Case-Control Studies, biology.protein, Female, business, Biomarkers
Abstract: Obesity, a major risk factor for endometrial cancer, is a low-grade inflammatory state characterized by elevated concentrations of cytokines and acute phase reactants. The current study had two aims: first to investigate the associations of C-reactive protein (CRP), interleukin 6 (IL6), and IL1 receptor antagonist (IL1Ra) with endometrial cancer risk and second to examine to which extent these markers can influence the association between obesity and endometrial cancer. We conducted a case–control study, nested within the European Prospective Investigation into Cancer and Nutrition, which comprised 305 incident cases of endometrial cancer and 574 matched controls. CRP, IL6, and IL1Ra were measured in prospectively collected blood specimens by immunoassays. Data were analyzed using conditional logistic regression. All statistical tests were two-sided, and P values Ptrend=0.02), IL6 (OR for top versus bottom quartile: 1.66, 95% CI: 1.08–2.54, Ptrend=0.008), and IL1Ra (OR for top versus bottom quartile: 1.82, 95% CI: 1.22–2.73, Ptrend=0.004). After adjustment for body mass index (BMI), the estimates were strongly reduced and became non-significant. The association between BMI and endometrial cancer was also substantially attenuated (∼10–20%) after adjustment for inflammatory markers, even when the effects of C-peptide or estrone had already been taken into account. We provided epidemiological evidence that chronic inflammation might mediate the association between obesity and endometrial cancer and that endometrial carcinogenesis could be promoted by an inflammatory milieu.
Published: 2016

18. Circulating 25-hydroxyvitamin D3 in relation to renal cell carcinoma incidence and survival in the EPIC cohort

Author: Carlos González, Per Magne Ueland, Domenico Palli, Anne Tjønneland, Laure Dossus, Marie-Christine Boutron-Ruault, Petra H.M. Peeters, Mattias Johansson, Kay-Tee Khaw, Salvatore Panico, H. Bas Bueno-de-Mesquita, Anja Olsen, Maria Wennberg, Börje Ljungberg, Miren Dorronsoro, Tilman Kühn, Dimitrios Trichopoulos, Elio Riboli, Elisabete Weiderpass, Anouar Fanidi, Ruth C. Travis, Heiner Boeing, Annika Steffen, Paul Brennan, Nicholas J. Wareham, Neil Murphy, Rosario Tumino, Maria Giotaki, Antonia Trichopoulou, Verena Katzke, Aurelio Barricarte, Gianluca Severi, Paolo Vineis, David C. Muller, Øivind Midttun, Vittorio Krogh, María José Sánchez, Ramón Alonso De La Torre, Carmen Santiuste, Muller, Dc, Fanidi, A, Midttun, O, Steffen, A, Dossus, L, Boutron Ruault, Mc, Severi, G, K?hn, T, Katzke, V, de la Torre, Ra, Gonz?lez, Ca, S?nchez, Mj, Dorronsoro, M, Santiuste, C, Barricarte, A, Khaw, Kt, Wareham, N, Travis, Rc, Trichopoulou, A, Giotaki, M, Trichopoulos, D, Palli, D, Krogh, V, Tumino, R, Vineis, P, Panico, Salvatore, Tj?nneland, A, Olsen, A, Bueno de Mesquita, Hb, Peeters, Ph, Ljungberg, B, Wennberg, M, Weiderpass, E, Murphy, N, Riboli, E, Ueland, Pm, Boeing, H, Brennan, P, and Johansson, M.
Subjects: Male, medicine.medical_specialty, Alcohol Drinking, Epidemiology, urologic and male genital diseases, Gastroenterology, White People, Body Mass Index, Sex Factors, Risk Factors, Internal medicine, medicine, Odds Ratio, Humans, Prospective Studies, Prospective cohort study, Carcinoma, Renal Cell, Survival analysis, Aged, Calcifediol, Proportional Hazards Models, Proportional hazards model, business.industry, Incidence, Smoking, Age Factors, Odds ratio, Middle Aged, Confidence interval, European Prospective Investigation into Cancer and Nutrition, Endocrinology, Logistic Models, Nested case-control study, Female, business, Body mass index
Abstract: Normal renal function is essential for vitamin D metabolism, but it is unclear whether circulating vitamin D is associated with risk of renal cell carcinoma (RCC). We assessed whether 25-hydroxyvitamin D3 (25(OH)D3) was associated with risk of RCC and death after RCC diagnosis in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC recruited 385,747 participants with blood samples between 1992 and 2000. The current study included 560 RCC cases, 557 individually matched controls, and 553 additional controls. Circulating 25(OH)D3 was assessed by mass spectrometry. Conditional and unconditional logistic regression models were used to calculate odds ratios and 95% confidence intervals. Death after RCC diagnosis was assessed using Cox proportional hazards models and flexible parametric survival models. A doubling of 25(OH)D3 was associated with 28% lower odds of RCC after adjustment for season of and age at blood collection, sex, and country of recruitment (odds ratio = 0.72, 95% confidence interval: 0.60, 0.86; P = 0.0004). This estimate was attenuated somewhat after additional adjustment for smoking status at baseline, circulating cotinine, body mass index (weight (kg)/height (m)(2)), and alcohol intake (odds ratio = 0.82, 95% confidence interval: 0.68, 0.99; P = 0.038). There was also some indication that both low and high 25(OH)D3 levels were associated with higher risk of death from any cause among RCC cases.
Published: 2016

19. Menopausal Hormone Therapy and Risk of Endometrial Carcinoma Among Postmenopausal Women in the European Prospective Investigation into Cancer and Nutrition

Author: Kim Overvad, Konstantinos K. Tsilidis, Eiliv Lund, Timothy J. Key, N. Charlotte Onland-Moret, Benedetta Bendinelli, H. Bas Bueno-de-Mesquita, Agnès Fournier, Kay-Tee Khaw, Salvatore Panico, Eric J. Duell, Alban Fabre, Anja Olsen, Aurelio Barricarte, Maria-Dolores Chirlaque, Rudolf Kaaks, Madlen Schuetze, Pilar Amiano, Vittorio Krogh, Carla H. van Gils, Françoise Clavel-Chapelon, Nathalie Chabbert-Buffet, Veronika Fedirko, Kjersti Bakken, Manuela M. Bergmann, Maria-Esther Molina-Montes, Anne Tjønneland, Elio Riboli, Laure Dossus, Naomi E. Allen, Dominique S. Michaud, Nicholas J. Wareham, María-Luisa Redondo, Traci Mouw, Fränzel J. B. van Duijnhoven, Carlotta Sacerdote, Rosario Tumino, Oxana Gavrilyuk, Sabina Rinaldi, Allen, Ne, Tsilidis, Kk, Key, Tj, Dossus, L, Kaaks, R, Lund, E, Bakken, K, Gavrilyuk, O, Overvad, K, Tjønneland, A, Olsen, A, Fournier, A, Fabre, A, Clavel Chapelon, F, Chabbert Buffet, N, Sacerdote, C, Krogh, V, Bendinelli, B, Tumino, R, Panico, Salvatore, Bergmann, M, Schuetze, M, van Duijnhoven, Fj, Bueno de Mesquita, Hb, Onland Moret, Nc, van Gils, Ch, Amiano, P, Barricarte, A, Chirlaque, Md, Molina Montes, Me, Redondo, Ml, Duell, Ej, Khaw, Kt, Wareham, N, Rinaldi, S, Fedirko, V, Mouw, T, Michaud, D, and Riboli, E.
Subjects: Oncology, medicine.medical_specialty, Norpregnenes, Epidemiology, medicine.drug_class, medicine.medical_treatment, Tibolone, Body Mass Index, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Estrogen Receptor Modulators, Risk Factors, Internal medicine, medicine, Humans, Risk factor, Aged, Proportional Hazards Models, Retrospective Studies, Gynecology, 030219 obstetrics & reproductive medicine, business.industry, Incidence, Endometrial cancer, Estrogen Replacement Therapy, Age Factors, Cancer, Middle Aged, medicine.disease, Endometrial Neoplasms, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, Postmenopause, Menopause, 030220 oncology & carcinogenesis, Female, Hormone therapy, business, Progestin, medicine.drug
Abstract: Udgivelsesdato: 2010-Oct-20 Estrogen-only menopausal hormone therapy (HT) increases the risk of endometrial cancer, but less is known about the association with other types of HT. Using Cox proportional hazards regression, the authors examined the association of various types of HT with the risk of endometrial cancer among 115,474 postmenopausal women recruited into the European Prospective Investigation into Cancer and Nutrition between 1992 and 2000. After a mean follow-up period of 9 years, 601 incident cases of endometrial cancer were identified. In comparison with never users of HT, risk of endometrial cancer was increased among current users of estrogen-only HT (hazard ratio (HR) = 2.52, 95% confidence interval (CI): 1.77, 3.57), tibolone (HR = 2.96, 95% CI: 1.67, 5.26), and, to a lesser extent, estrogen-plus-progestin HT (HR = 1.41, 95% CI: 1.08, 1.83), although risks differed according to regimen and type of progestin constituent. The association of HT use with risk was stronger among women who were older, leaner, or had ever smoked cigarettes. The finding of a strong increased risk of endometrial cancer with estrogen-only HT and a weaker association with combined HT supports the hypothesis that progestins have an attenuating effect on endometrial cancer risk. The increased risk associated with tibolone use requires further investigation.
Published: 2010

20. Serum IGF-I, its major binding protein (IGFBP-3) and epithelial ovarian cancer risk: the European Prospective Investigation into Cancer and Nutrition (EPIC)

Author: Jakob Linseisen, Carla H. van Gils, Françoise Clavel, Elio Riboli, Göran Berglund, Annekatrin Lukanova, H. Bas Bueno-de-Mesquita, Timothy J. Key, Salvatore Panico, Mandy Schulz, Petra H.M. Peeters, Dimitrios Trichopolos, Kim Overvad, Eva Lundin, Christina Bamia, Carmen Navarro, Anja Olsen, Nerea Larrañaga, Anne Tjønneland, Laure Dossus, Domenico Palli, Carmen Martinez-Garcia, Kay-Tee Khaw, Jenny Chang-Claude, Mette Skytte Tetsche, J. Ramón Quirós, Eva Ardanaz, Guillem Pera, Rosario Tumino, Carlotta Sacerdote, Franco Berrino, Sabina Rinaldi, Rudolf Kaaks, Heiner Boeing, Eiliv Lund, Naomi E. Allen, Sheila Bingham, Antonia Trichopoulou, Peeters, Ph, Lukanova, A, Allen, N, Berrino, F, Key, T, Dossus, L, Rinaldi, S, VAN GILS, Ch, BUENO DE MESQUITA, Hb, Boeing, H, Schulz, M, CHANG CLAUDE, J, Linseisen, J, Panico, Salvatore, Sacerdote, C, Palli, D, Tumino, R, Trichopoulou, A, Trichopolos, D, Bamia, C, Larranaga, N, Ardanaz, E, Pera, G, Quiros, Jr, MARTINEZ GARCIA, C, Navarro, C, Bingham, Sa, Khaw, Kt, Clavel, F, Tjonneland, A, Olsen, A, Overvad, K, Tetsche, M, Lund, E, Lundin, E, Berglund, G, Riboli, E, and Kaaks, R.
Subjects: Adult, Oncology, Cancer Research, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Biology, Endocrinology, Risk Factors, Internal medicine, medicine, Humans, Neoplasms, Glandular and Epithelial, Prospective Studies, ddc:610, Insulin-Like Growth Factor I, Prospective cohort study, Aged, Ovarian Neoplasms, Case-control study, Odds ratio, Middle Aged, medicine.disease, European Prospective Investigation into Cancer and Nutrition, Europe, Insulin-Like Growth Factor Binding Protein 3, Premenopause, Case-Control Studies, Relative risk, Female, Ovarian cancer, Body mass index, Hormone
Abstract: We set out to study the relationship between circulating levels of IGF-I and its major binding protein (IGFBP-3) in relation to ovarian cancer risk. We conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition. Levels of IGF-I and IGFBP-3 were measured in prediagnostic serum samples of 214 women who subsequently developed ovarian cancer, and 388 matched control subjects. Conditional logistic regression models were used to estimate relative risks of ovarian cancer by tertiles of IGF-I and IGFBP-3 levels. For all women, there was no association between the circulating IGF-I or IGFBP-3 levels and the risk of ovarian cancer. However, among women diagnosed with ovarian cancer aged 55 or younger, the relative risk was higher in the middle or top tertiles of serum IGF-I, when compared with women in the lowest tertile (odds ratios (OR) = 1.8 (95%CI 0.7–4.3) and OR = 2.4 (95%CI 0.9–6.4); Ptrend = 0.08) respectively. These results were adjusted for body mass index, previous hormone use, fertility problems, and parity. Restricting the analysis to women who were premenopausal at blood donation, relative risks for ovarian cancer diagnosed before age 55 were higher (OR = 5.1 (95%CI 1.5–18.2) and OR = 5.6 (95%CI 1.5–20.8) respectively, for second and third tertiles; Ptrend = 0.02). Adjustment for serum IGFBP-3 levels only slightly attenuated relative risk estimates. Relations between IGFBP-3 and ovarian cancer before age 55 were in the same direction as for IGF-I, but less strong and statistically not significant. In women aged over 55, there was no association between serum IGF-I or IGFBP-3 and ovarian cancer risk. Our results suggest that the circulating levels of IGF-I may play a potentially important role in the development of ovarian cancer in women of a pre- or perimenopausal age.
Published: 2007

21. Pre-diagnostic concordance with the WCRF/AICR guidelines and survival in European colorectal cancer patients: a cohort study

Author: Carla H. van Gils, E. Riboli, Christos Tsironis, Anne-Claire Vergnaud, H. Bas Bueno-de-Mesquita, Laureen Dartois, José Ramón Quirós, Veronika Fedirko, Pietro Ferrari, Teresa Norat, Pagona Lagiou, Christina C. Dahm, Giovanna Masala, Timothy J. Key, Mark J. Gunter, Maria Wennberg, Kay-Tee Khaw, Verena Katzke, Petra H.M. Peeters, Aurelio Barricarte, Heather Ward, Nicholas J. Wareham, Anne Tjønneland, Lena Maria Nilsson, Bodil Ohlsson, Valeria Pala, Laure Dossus, Antonia Trichopoulou, Tilman Kühn, Heiner Boeing, Elisabete Weiderpass, Petra A. Wark, M. Dorronsoro, Carmen Navarro, Camilla Plambeck Hansen, Genevieve Buckland, Salvatore Panico, Marie-Christine Boutron-Ruault, María José Sánchez, Paolo Vineis, Peter D. Siersema, Karin Jirström, Dora Romaguera, Rosario Tumino, Mazda Jenab, Romaguera, Dora, Ward, Heather, Wark, Petra A, Vergnaud, Anne Claire, Peeters, Petra H, van Gils, Carla H, Ferrari, Pietro, Fedirko, Veronika, Jenab, Mazda, Boutron Ruault, Marie Christine, Dossus, Laure, Dartois, Laureen, Hansen, Camilla Plambeck, Dahm, Christina Catherine, Buckland, Genevieve, Sánchez, María José, Dorronsoro, Miren, Navarro, Carmen, Barricarte, Aurelio, Key, Timothy J, Trichopoulou, Antonia, Tsironis, Christo, Lagiou, Pagona, Masala, Giovanna, Pala, Valeria, Tumino, Rosario, Vineis, Paolo, Panico, Salvatore, Bueno de Mesquita, H. Ba, Siersema, Peter D, Ohlsson, Bodil, Jirström, Karin, Wennberg, Maria, Nilsson, Lena M, Weiderpass, Elisabete, Kühn, Tilman, Katzke, Verena, Khaw, Kay Tee, Wareham, Nick J, Tjønneland, Anne, Boeing, Heiner, Quirós, José R, Gunter, Marc J, Riboli, Elio, Norat, Teresa, Department of Medical and Clinical Genetics, Medicum, BMC, BMC, Department of Epidemiology and Public Health, Imperial College London, Instituto de Investigación Sanitaria de Palma (IdISPa), Hospital Universitario Son Espases, CIBER Fisiopatología de la Obesidad y Nutrición ( (CIBEROBN)), Instituto de Salud Carlos III [Madrid] (ISC), Department of Primary Care and Public Health, Department of Epidemiology, University Medical Center [Utrecht]-Julius Center for Health Sciences and Primary Care, Nutrition and Metabolism Section, International Agency for Cancer Research (IACR), Emory University [Atlanta, GA]-Rollins School of Public Health-Winship Cancer Institute, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Section for Epidemiology, Aarhus University [Aarhus], Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology (ICO-IDIBELL)-Cancer Epidemiology Research Programme, Granada Cancer Registry, Andalusian School of Public Health [Granada], Consorcio de Investigación Biomédica en Red especializado en Epidemiología y Salud Pública (CIBERESP), Los Centros de Investigación Biomédica en Red (CIBER), Murcia Regional Health Council [Murcia], Department of Health and Social Sciences, Universidad de Murcia, Navarre Public Health Institute, Cancer Epidemiology Unit, University of Oxford, Hellenic Health Foundation, Bureau of Epidemiologic Research, Academy of Athens, Department of Hygiene, Epidemiology and Medical Statistics, Harvard School of Public Health, Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute-ISPO, Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], Cancer Registry and Histopathology Unit, Department of Oncology-Civile - M.P.Arezzo Hospital, Human Genetics Foundation (HuGeF), Università degli studi di Torino = University of Turin (UNITO), Dipartimento di Medicina Clinica e Chirurgia, University of Naples Federico II = Università degli studi di Napoli Federico II, Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya = Universiti Malaya [Kuala Lumpur, Malaisie] (UM), Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment [Bilthoven] (RIVM), Department of Gastroenterology and Hepatology, University Medical Center [Utrecht], Division of Internal Medicine, Skane University Hospital [Malmo], Lund University [Lund]-Lund University [Lund], Division of Oncology and Pathology, Lund University [Lund], Department of Public Health and Clinical Medicine, Nutritional Research, Umeå University, Arctic Research Centre, Department of Community Medicine, The Arctic University of Norway [Tromsø, Norway] (UiT), Department of Research, Cancer Registry of Norway, Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Genetic Epidemiology Group [Helsinki], Folkhälsan Research Center, Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Division of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Clinical Gerontology Unit, University of Cambridge [UK] (CAM), MRC Epidemiology Unit, University of Cambridge [UK] (CAM)-Institute of Metabolic Science, Danish Cancer Society Research Center, German Institute of Human Nutrition (DIfE) Potsdam-Rehbrücke, Public Health Directorate, Khaw, Kay-Tee [0000-0002-8802-2903], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), University of Oxford [Oxford], Università degli studi di Torino (UNITO), University of Naples Federico II, University of Malaya, The Arctic University of Norway, University of Helsinki-University of Helsinki-Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki, [Romaguera,D, Ward,H, Vergnaud,A, Peeters,PH, Vineis,P, Bueno-de-Mesquita,HB, Gunter, MJ, Riboli,E, Norat,T] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Romaguera,D] Instituto de Investigación Sanitaria de Palma (IdISPa), Hospital Universitario Son Espases, Palma de Mallorca, Spain. [Romaguera,D] CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain. [Wark,PA] Global eHealth Unit, Department of Primary Care and Public Health, School of Public Health, Imperial College London, London, UK. [Peeters,PH, Gils, CH] Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. [Ferrari,P, Jenab,M] International Agency for Cancer Research (IARC), Lyon CEDEX, France. [Fedirko,V] Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, USA. [Fedirko,V] Winship Cancer Institute, Emory University, Atlanta, USA. [Boutron-Ruault,M, Dossus,L, Dartois,L] Inserm (Institut National de la Santé et de la Recherche Médicale), Centre for Research in Epidemiology and Population Health (CESP), Vaillant, Villejuif, Cedex, France. [Boutron-Ruault,M, Dartois,L] Univ Paris Sud, Villejuif, France. [Boutron-Ruault,M, Dartois,L] Gustave Roussy, Villejuif, France. [Hansen,CP, Dahm,CC] Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus C, Denmark. [Buckland,G] Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain. [Sánchez,MJ] Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs. GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain. [Sánchez,MJ, Dorronsoro,M, Navarro,C, Barricarte,A] CIBER de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain. [Dorronsoro,M] Public Health Direction and Biodonostia Basque Regional Health Department, San Sebastian, Spain. [Navarro,C] Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain. Department of Health and Social Sciences, Universidad de Murcia, Campus Universitario de Espinardo, Murcia, Spain. [Barricarte,A] Navarre Public Health Institute, Pamplona, Spain. [Key,TJ] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford UK. [Trichopoulou,A, Tsironis,C] Hellenic Health Foundation, Athens, Greece . [Trichopoulou,A, Lagiou,P] Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. [Lagiou,P] Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. [Lagiou,P] Department of Epidemiology, Harvard School of Public Health, Boston, USA. [Masala,G] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute – ISPO, Florence, Italy. [Pala,V] Epidemiology and Prevention Unit, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy. [Tumino,R] Cancer Registry and Histopathology Unit, 'Civic – M.P. Arezzo' Hospital, Ragusa, Italy. [Vineis,P] HuGeF Foundation, Turin, Italy. [Panico,S] Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy. [Bueno-de-Mesquita,HB] Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven The Netherlands. [Bueno-de-Mesquita,HB, Siersema,PD] Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands. [Bueno-de-Mesquita,HB] Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. [Ohlsson,B] Division of Internal Medicine, Department of Clinical Sciences, Skane University Hospital, Malmo, Lund University, Lund, Sweden. [Jirström,K] Department of Clinical Sciences, Division of Oncology and Pathology, Lund University, Lund, Sweden. [Wennberg,M] Public Health and Clinical Medicine, Nutritional Research, Umeå University, Umeå, Sweden. [Nilsson,LM] Arctic Research Centre, Umeå University, Umeå, Sweden. [Weiderpass,E] Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, ISM - Universitetet i Tromsø, Tromsø, Norway. Department of Research, Cancer Registry of Norway, Majorstuen Oslo, Norway. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Department of Genetic Epidemiology, Folkhälsan Research Center, Folkhälsan Research Center, Biomedicum 1, University of Helsinki, Helsinki, Finland. [Kühn,T, Katzke,V] German Cancer Research Center (DKFZ), Division of Cancer Epidemiology Im Neuenheimer Feld 581, Heidelberg, Germany. [Khaw,K] University of Cambridge School of Clinical Medicine, Clinical Gerontology Unit Box 251, Addenbrooke’s Hospital, Cambridge, UK. [Wareham,NJ] MRC Epidemiology Unit, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK. [Tjønneland,A] Danish Cancer Society Research Center, Copenhagen, Denmark. [Boeing,H] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany. [Quirós,JR] Public Health Directorate, Oviedo Asturias, Spain., This study was funded by the World Cancer Research Fund (WCRF) International Regular Grant Programme (Grant number 2009/44). Dora Romaguera holds a Ramon y Cajal contract (Ministerio de Economía y Competitividad, Spain and European Regional Development Fund, RYC-2011-08796). In addition, EPIC investigators acknowledge funding from the following agencies: Europe Against Cancer Program of the European Commission (SANCO), German Cancer Aid, German Cancer Research Center (DKFZ), German Federal Ministry of Education and Research (BMBF), Danish Cancer Society, Catalan Institute of Oncology, Spain, Health Research Fund (FIS) of the Spanish Ministry of Health, Spanish Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236) and Navarra, ISCIII RCESP exp. C03/09 and ISCIII RETICC RD06/0020/0091, Spain, Cancer Research UK, Medical Research Council, United Kingdom, The Hellenic Health Foundation, Greece, Italian Association for Research on Cancer (AIRC), Italian National Research Council, Fondazione-Istituto Banco Napoli, Italy, Dutch Ministry of Public Health, Welfare and Sports, Dutch Prevention Funds, LK Research Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), The Netherlands, Swedish Cancer Society, Swedish Scientific Council, Regional Government of Skåne, Sweden, Helga—Nordic Center of Excellence Programme in Nutrition and Health, French League against Cancer (LNCC), National Institute for Health and Medical Research (INSERM), France, Mutuelle Générale de l'Education Romaguera et al. BMC Medicine (2015) 13:107 Page 10 of 12 Nationale (MGEN), France, 3 M Co., France, Gustave Roussy Institute (IGR), France, and and General Councils of France. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Subjects: Male, physical activity, 0302 clinical medicine, estudios prospectivos, Prospective Studies, estudios de cohortes, mediana edad, Aged, 80 and over, anciano, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Motor Activity [Medical Subject Headings], dieta, Incidence, Hazard ratio, COLON-CANCER, General Medicine, adulto, 3. Good health, Näringslära, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, estilo de vida, Cohort, Dieta, Estilo de Vida, RESEARCH FUND/AMERICAN INSTITUTE, Cohort study, Human, medicine.medical_specialty, Concordance, European Continental Ancestry Group, DIAGNOSIS, incidencia, White People, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Càncer colorectal, Neoplasias Colorrectales, BREAST-CANCER, Humans, Life Style, Aged, Cancer prevention, Proportional hazards model, Physical activity, Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [Medical Subject Headings], Psychiatry and Psychology::Behavior and Behavior Mechanisms::Psychology, Social::Life Style [Medical Subject Headings], weight, LIFE-STYLE FACTORS, Colorectal cancer, REPRODUCTIVE HISTORY, Prospective Studie, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Cancer and Oncology, Proportional Hazards Model, grupo de ascendencia continental europea, Estudios de Cohortes, Gerontology, cumplimiento del paciente, Survival, modelos de riesgos proporcionales, VDP::Medisinske Fag: 700::Helsefag: 800::Epidemiologi medisinsk og odontologisk statistikk: 803, [SDV]Life Sciences [q-bio], humanos, Colorectal Neoplasm, Alcohol consumption, Breast cancer, Prospective study, Named Groups::Persons::Survivors [Medical Subject Headings], Cohort Studies, 030212 general & internal medicine, Prospective cohort study, Non-U.S. Gov't, 2. Zero hunger, Medicine(all), RISK, Nutrition and Dietetics, Healthy lifestyle, Diet, Weight, Research Support, Non-U.S. Gov't, Public Health, Global Health, Social Medicine and Epidemiology, Middle Aged, European Prospective Investigation into Cancer and Nutrition, VDP::Medical disciplines: 700::Health sciences: 800::Epidemiology medical and dental statistics: 803, NUTRITION, Female, Colorectal Neoplasms, Research Article, Adult, neoplasias colorrectales, 3122 Cancers, RECREATIONAL PHYSICAL-ACTIVITY, Other Research Radboud Institute for Molecular Life Sciences [Radboudumc 0], colorectal cancer, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings], Research Support, survival, Sobrevivientes, healthy lifestyle, Internal medicine, medicine, Journal Article, Proportional Hazards Models, Actividad Motora, business.industry, Physical fitness, BODY-MASS INDEX, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Other Clinical Medicine, 3121 General medicine, internal medicine and other clinical medicine, Patient Compliance, Cohort Studie, business, diet, Condició física
Abstract: Background: Cancer survivors are advised to follow lifestyle recommendations on diet, physical activity, and body fatness proposed by the World Cancer Research Fund/American Institute of Cancer Research (WCRF/AICR) for cancer prevention. Previous studies have demonstrated that higher concordance with these recommendations measured using an index score (the WCRF/AICR score) was associated with lower cancer incidence and mortality. The aim of this study was to evaluate the association between pre-diagnostic concordance with WCRF/AICR recommendations and mortality in colorectal cancer (CRC) patients. Methods: The association between the WCRF/AICR score (score range 0-6 in men and 0-7 in women; higher scores indicate greater concordance) assessed on average 6.4 years before diagnosis and CRC-specific (n = 872) and overall mortality (n = 1,113) was prospectively examined among 3,292 participants diagnosed with CRC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (mean follow-up time after diagnosis 4.2 years). Multivariable Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality. Results: The HRs (95% CIs) for CRC-specific mortality among participants in the second (score range in men/women: 2.25-2.75/3.25-3.75), third (3-3.75/4-4.75), and fourth (4-6/5-7) categories of the score were 0.87 (0.72-1.06), 0.74 (0.61-0.90), and 0.70 (0.56-0.89), respectively (P for trend, We would like to acknowledge the contribution of all participants in the study. This study was funded by the World Cancer Research Fund (WCRF) International Regular Grant Programme (Grant number 2009/44). Dora Romaguera holds a Ramon y Cajal contract (Ministerio de Economia y Competitividad, Spain and European Regional Development Fund; RYC-2011-08796). In addition, EPIC investigators acknowledge funding from the following agencies: Europe Against Cancer Program of the European Commission (SANCO); German Cancer Aid; German Cancer Research Center (DKFZ); German Federal Ministry of Education and Research (BMBF); Danish Cancer Society; Catalan Institute of Oncology, Spain; Health Research Fund (FIS) of the Spanish Ministry of Health; Spanish Regional Governments of Andalucia, Asturias, Basque Country, Murcia (no. 6236) and Navarra; ISCIII RCESP exp. C03/09 and ISCIII RETICC RD06/0020/0091, Spain; Cancer Research UK; Medical Research Council, United Kingdom; The Hellenic Health Foundation, Greece; Italian Association for Research on Cancer (AIRC); Italian National Research Council; Fondazione-Istituto Banco Napoli, Italy; Dutch Ministry of Public Health, Welfare and Sports, Dutch Prevention Funds, LK Research Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), The Netherlands; Swedish Cancer Society; Swedish Scientific Council; Regional Government of Skane, Sweden; Helga-Nordic Center of Excellence Programme in Nutrition and Health; French League against Cancer (LNCC); National Institute for Health and Medical Research (INSERM), France; Mutuelle Generale de l'Education Nationale (MGEN), France; 3 M Co., France; Gustave Roussy Institute (IGR), France; and General Councils of France.
Published: 2014

22. C-peptide, IGF-I, sex-steroid hormones and adiposity

Author: Petra H.M. Peeters, Naomi E. Allen, H. Bas Bueno-de-Mesquita, Valeria Pala, Françoise Clavel-Chapelon, Anne Tjønneland, Laure Dossus, Gabriele Nagel, Teresa Norat, Kim Overvad, M. J. Tormo, J. R. Quirós, Carmen Martinez-Garcia, Irene D. Bezemer, Sheila Bingham, Antonio Agudo, Søren Paaske Johnsen, Bertrand Hémon, Antonia Trichopoulou, Anja Olsen, Paolo Vineis, Carla H. van Gils, Nikos Baibas, Sabina Rinaldi, Eva Ardanaz, Petra H. Lahmann, Heiner Boeing, D. Zilis, Rosario Tumino, Emmanuelle Kesse, Salvatore Panico, Elio Riboli, Bertrand Tehard, Paulus A.H. van Noord, Jakob Linseisen, Andrew W. Roddam, Rudolf Kaaks, Pilar Amiano, Kay-Tee Khaw, Domenico Palli, University of Groningen, Bezemer, Id, Rinaldi, S, Dossus, L, Gils, Ch, Peeters, Ph, Noord, Pa, BUENO DE MESQUITA, Hb, Johnsen, Sp, Overvad, K, Olsen, A, Tjonneland, A, Boeing, H, Lahmann, Ph, Linseisen, J, Nagel, G, Allen, N, Roddam, A, Bingham, S, Khaw, Kt, Kesse, E, Tehard, B, CLAVEL CHAPELON, F, Agudo, A, Ardanaz, E, Quiros, Jr, Amiano, P, C., Mg, Tormo, Mj, Pala, V, Panico, Salvatore, Vineis, P, Palli, D, Tumino, R, Trichopoulou, A, Baibas, N, Zilis, D, Hemon, B, Norat, T, Riboli, E, and Kaaks, R.
Subjects: Cancer Research, medicine.medical_treatment, FACTOR (IGF)-I, Body Mass Index, chemistry.chemical_compound, Sex hormone-binding globulin, Sex Hormone-Binding Globulin, Prospective Studies, Insulin-Like Growth Factor I, BINDING PROTEIN-3, anthropometry, biology, C-Peptide, C-peptide, Middle Aged, POLYCYSTIC-OVARY-SYNDROME, sex-steroid hormones, European Prospective Investigation into Cancer and Nutrition, IGF-I, Postmenopause, Oncology, POSTMENOPAUSAL WOMEN, PREMENOPAUSAL WOMEN, Androgens, Female, LIFE-STYLE, ENERGY-BALANCE, hormones, hormone substitutes, and hormone antagonists, medicine.medical_specialty, insulin, medicine.drug_class, Internal medicine, GROWTH-FACTOR-I, medicine, Humans, BREAST-CANCER, ddc:610, business.industry, Waist-Hip Ratio, Insulin, Estrogens, Androgen, BODY-MASS INDEX, Endocrinology, Cross-Sectional Studies, Insulin-Like Growth Factor Binding Protein 3, chemistry, Premenopause, Sex steroid, biology.protein, business, Body mass index, Hormone
Abstract: Objectives: The risk of some cancers is positively associated with body weight, which may influence circulating levels of sex-steroid hormones, insulin and IGF-I. Interrelationships between these hormones and the associations with adiposity were evaluated in healthy women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC).Methods: A cross-sectional analysis was performed on anthropometric and hormonal data from 743 pre- and 1217 postmenopausal women. Body mass index (BMI) and waist circumference were used as indicators of adiposity. C-peptide, Insulin Growth Factor (IGF)-I, Insulin Growth Factor binding protein (IGFBP)-3, androgens, estrogens and sex hormone binding globulin (SHBG) were measured by immunoassays; free sex steroid concentrations were calculated.Results: BMI and waist circumference were positively correlated with estrogens in postmenopausal women and with C-peptide, free testosterone and inversely with SHBG in all women. C-peptide and IGF-I were inversely correlated with SHBG, and positively with free sex steroids in postmenopausal women. IGF-I was positively associated with postmenopausal estrogens and androgen concentrations in all women.Conclusions: Sex-steroid concentrations appear to be regulated along several axes. Adiposity correlated directly with estrogens in postmenopausal women and with insulin, resulting in lower SHBG and increased levels of free sex steroids. Independent of adiposity and insulin, IGF-I was associated with decreased SHBG levels, and increased concentrations of androgens and postmenopausal estrogens.
Published: 2005

23. Fruit and vegetable intake and cause-specific mortality in the EPIC study

Author: Nicholas J. Wareham, Kathryn E. Bradbury, Mattias Johansson, Petra H.M. Peeters, Isabel Drake, Emily Sonestedt, José María Huerta, Idlir Licaj, H. Bas Bueno-de-Mesquita, Rudolf Kaaks, Dagrun Engeset, Pagona Lagiou, Anja Olsen, Tonje Braaten, Kim Overvad, Ingegerd Johansson, Antonio Agudo, Kuanrong Li, Anne Tjønneland, Neil Murphy, Laure Dossus, Antonia Trichopoulou, Maria Luisa Redondo, Elio Riboli, Peter D. Siersema, Elisabete Weiderpass, Heiner Boeing, Anna Winkvist, Dimitrios Trichopoulos, Eva Ardanaz, Laureen Dartois, Salvatore Panico, Max Leenders, Rosario Tumino, Pilar Amiano, Paolo Vineis, Kay-Tee Khaw, Domenico Palli, Marie-Christine Boutron-Ruault, Pietro Ferrari, Timothy J. Key, Marc J. Gunter, Vittorio Krogh, María José Sánchez, Hendriek C. Boshuizen, Manuela M. Bergmann, IRAS RATIA-SIB, LS IRAS EEPI GRA (Gezh.risico-analyse), Risk Assessment of Toxic and Immunomodulatory Agents, Leenders, M, Boshuizen, Hc, Ferrari, P, Siersema, Pd, Overvad, K, Tj?nneland, A, Olsen, A, Boutron Ruault, Mc, Dossus, L, Dartois, L, Kaaks, R, Li, K, Boeing, H, Bergmann, Mm, Trichopoulou, A, Lagiou, P, Trichopoulos, D, Palli, D, Krogh, V, Panico, Salvatore, Tumino, R, Vineis, P, Peeters, Ph, Weiderpass, E, Engeset, D, Braaten, T, Redondo, Ml, Agudo, A, S?nchez, Mj, Amiano, P, Huerta, Jm, Ardanaz, E, Drake, I, Sonestedt, E, Johansson, I, Winkvist, A, Khaw, Kt, Wareham, Nj, Key, Tj, Bradbury, Ke, Johansson, M, Licaj, I, Gunter, Mj, Murphy, N, Riboli, E, and Bueno de Mesquita, Hb
Subjects: Male, Nutrition and Disease, Epidemiology, Disease, Wiskundige en Statistische Methoden - Biometris, project, Risk Factors, Voeding en Ziekte, Cause of Death, Neoplasms, Surveys and Questionnaires, Vegetables, Prospective Studies, cardiovascular-disease mortality, Cause of death, risk, education.field_of_study, Incidence (epidemiology), Incidence, Hazard ratio, Middle Aged, PE&RC, European Prospective Investigation into Cancer and Nutrition, Europe, nutrition, Cardiovascular Diseases, all-cause, Female, dietary-intake measurements, Adult, medicine.medical_specialty, cancer-mortality, Population, Lower risk, Diet Surveys, Environmental health, medicine, Humans, education, Mathematical and Statistical Methods - Biometris, Life Style, Aged, Proportional Hazards Models, hiroshima/nagasaki life-span, business.industry, Proportional hazards model, Feeding Behavior, heart-disease, Surgery, Diet, european countries, Fruit, business
Abstract: Consumption of fruits and vegetables is associated with a lower overall mortality. The aim of this study was to identify causes of death through which this association is established. More than 450,000 participants from the European Prospective Investigation into Cancer and Nutrition study were included, of which 25,682 were reported deceased after 13 years of follow-up. Information on lifestyle, diet and vital status was collected through questionnaires and population registries. Hazard ratios (HR) with 95 % confidence intervals (95 % CI) for death from specific causes were calculated from Cox regression models, adjusted for potential confounders. Participants reporting consumption of more than 569 g/day of fruits and vegetables had lower risks of death from diseases of the circulatory (HR for upper fourth 0.85, 95 % CI 0.77-0.93), respiratory (HR for upper fourth 0.73, 95 % CI 0.59-0.91) and digestive system (HR for upper fourth 0.60, 95 % CI 0.46-0.79) when compared with participants consuming less than 249 g/day. In contrast, a positive association with death from diseases of the nervous system was observed. Inverse associations were generally observed for vegetable, but not for fruit consumption. Associations were more pronounced for raw vegetable consumption, when compared with cooked vegetable consumption. Raw vegetable consumption was additionally inversely associated with death from neoplasms and mental and behavioral disorders. The lower risk of death associated with a higher consumption of fruits and vegetables may be derived from inverse associations with diseases of the circulatory, respiratory and digestive system, and may depend on the preparation of vegetables and lifestyle factors.
Published: 2014

24. Thyroid-Stimulating Hormone, Thyroglobulin, and Thyroid Hormones and Risk of Differentiated Thyroid Carcinoma: The EPIC Study

Author: Salvatore Panico, Petra H.M. Peeters, Domenico Palli, Ruth C. Travis, Graham Byrnes, Augustin Scalbert, Eiliv Lund, Dimitrios Trichopoulos, Kim Overvad, Martin Almquist, Pagona Lagiou, Heiner Boeing, Anne Tjønneland, Annekatrin Lukanova, H. Bas Bueno-de-Mesquita, Carine Biessy, Rudolf Kaaks, Julie Kathrine Schmidt, Laure Dossus, Carmen Navarro, Martyn Plummer, Elisabete Weiderpass, Jytte Halkjær, Joakim Hennings, Nerea Larrañaga, Marie-Christine Boutron-Ruault, Antonio Agudo, Isabelle Romieu, Rosario Tumino, Kay-Tee Khaw, Silvia Franceschi, Claudia Agnoli, Elio Riboli, Antonia Trichopoulou, Jane Nautrup Østergaard, Jonas Manjer, Paolo Vineis, Maria Sandström, Esther Molina, Françoise Clavel-Chapelon, Konstantinos K. Tsilidis, J. Ramón Quirós, Eva Ardanaz, Marc J. Gunter, Sabina Rinaldi, Rinaldi, S, Plummer, M, Biessy, C, Tsilidis, Kk, stergaard, Jn, Overvad, K, Tj?nneland, A, Halkjaer, J, Boutron Ruault, Mc, Clavel Chapelon, F, Dossus, L, Kaaks, R, Lukanova, A, Boeing, H, Trichopoulou, A, Lagiou, P, Trichopoulos, D, Palli, D, Agnoli, C, Tumino, R, Vineis, P, Panico, Salvatore, Bueno de Mesquita, Hb, Peeters, Ph, Weiderpass, E, Lund, E, Quir?s, Jr, Agudo, A, Molina, E, Larra?aga, N, Navarro, C, Ardanaz, E, Manjer, J, Almquist, M, Sandstr?m, M, Hennings, J, Khaw, Kt, Schmidt, J, Travis, Rc, Byrnes, G, Scalbert, A, Romieu, I, Gunter, M, Riboli, E, and Franceschi, S.
Subjects: Adult, Male, Thyroid Hormones, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, Thyrotropin, Thyroid Function Tests, Risk Assessment, Thyroglobulin, Thyroid function tests, Sampling Studies, Thyroid carcinoma, Thyroid-stimulating hormone, Predictive Value of Tests, Risk Factors, Internal medicine, Biomarkers, Tumor, Odds Ratio, medicine, Humans, Thyroid Neoplasms, Aged, Autoantibodies, Thyroid-stimulating hormone measurement, medicine.diagnostic_test, business.industry, Incidence, Carcinoma, Case-control study, Odds ratio, Middle Aged, Logistic Models, Endocrinology, Oncology, Case-Control Studies, Female, business, Hormone
Abstract: BACKGROUND: Increased levels of thyroglobulin (Tg) and thyroid-stimulating hormone (TSH) are associated with differentiated thyroid carcinoma (TC) risk, but strong epidemiological evidence is lacking.METHODS: Three hundred fifty-seven incident TC case patients (n = 300 women and 57 men; mean age at blood collection = 51.5 years) were identified in the EPIC cohort study and matched with 2 (women) or 3 (men) control subjects using incidence density sampling. Matching included study center, sex, age, date, time, and fasting status at blood collection. Levels of total and free (f) thyroxine (T4) and triiodo-thyronine (T3), TSH, Tg, and anti-Tg antibodies (TgAb) were measured by commercially available immunoassays. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed using conditional logistic regression. All statistical tests were two-sided.RESULTS: TC risk was positively associated with Tg (OR for the highest vs lowest quartile = 9.15; 95% CI = 5.28 to 15.90; P < .001) and negatively associated with TSH level (OR = 0.56; 95% CI = 0.38 to 0.81; P = .001). Odds ratios were not modified by adjustment for weight and height and were consistent across sexes, age groups, and countries. The association with Tg was stronger in follicular than papillary TC. The odds ratio for TgAb-positivity was 1.50 (95% CI = 1.05 to 2.15; P = .03). Among case patients, TSH level was stable over time, whereas Tg level was higher in proximity to TC diagnosis. Areas under the receiver operating characteristic curve were 57% and 74% for TSH and Tg level, respectively.CONCLUSIONS: High Tg levels precede by up to 8 years the detection of TC, pointing to a long sojourn time of the disease. Low TSH levels may predispose to TC onset. Neither marker has sufficient accuracy to be a screening test.
Published: 2014

25. Lifetime alcohol use and overall and cause-specific mortality in the European Prospective Investigation into Cancer and nutrition (EPIC) study

Author: Vasiliki Benetou, Isabelle Romieu, Antonia Trichopoulou, Teresa Norat, Joline W.J. Beulens, Kim Overvad, Larraitz Arriola, Elisabete Weiderpass, Eric J. Duell, Aurelio Barricarte, Paul Brennan, Anne Tjønneland, Peter Wallström, Rosario Tumino, Mattias Johansson, Guy Fagherazzi, Laure Dossus, Petra H.M. Peeters, Marc J. Gunter, Dimitrios Trichopoulos, David C. Muller, Carlotta Sacerdote, Laureen Dartois, Elio Riboli, Nicholas J. Wareham, Pietro Ferrari, Claudia Agnoli, Idlir Licaj, Anja Olsen, Esther Molina-Montes, Domenico Palli, Per Kragh Andersen, Kathryn E. Bradbury, Kuanrong Li, Heiner Boeing, Luciana Neves Nunes, Rudolf Kaaks, Carmen Navarro Sánchez, Kay-Tee Khaw, [Ferrari,P, Licaj,I, Muller,DC, Johansson,M, Nunes,L, Brennan,P, Romieu,I] International Agency for Research on Cancer, Lyon, France. [Andersen,PK] Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark. [Boeing,H] Potsdam-Rehbrücke Department of Epidemiology, German Institute of Human Nutrition, Nuthetal, Germany. [Weiderpass,E] Department of Community Medicine, Faculty of Health Sciences, University of Tromso, The Arctic University of Norway, Tromsø, Norway. Department of Research, Cancer Registry of Norway, Oslo, Norway. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Samfundet Folkhälsan, Helsinki, Finland. [Dossus,L, Dartois,L, Fagherazzi,G] Inserm, Centre for research in Epidemiology and Population Health (CESP), U1018, Nutrition, Hormones and Women’s Health team, Villejuif, France. Université Paris Sud, UMRS 1018, Villejuif, France. IGR, Villejuif, France. [Bradbury,KE] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK. [Khaw,K] Department of Public Health and Primary Care, University of Cambridge Addenbrooke’s Hospital, Cambridge, UK. [Wareham,N] Medical Research Council Epidemiology Unit, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, UK. [Duell,EJ] Unit of Nutrition, Cancer Epidemiology Research Program, Environment and Cancer, Bellvitge Biomedical Research Institute (IDIBELL), Catalan Institute of Oncology (ICO), Barcelona, Spain. [Barricarte,A] Navarre Public Health Institute, Pamplona, Spain. [Barricarte,A, Arriola,L] Consortium for Biomedical Research in Epidemiology and Public Health (CIBER Epidemiología y Salud Pública-CIBERESP), Murcia, Spain. [Molina-Montes,E] Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria de Granada, Granada, Spain. [Molina-Montes,E, Navarro,C] CIBER Epidemiología y Salud Pública (CIBERESP), Spain. [Navarro,C] Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain. Department of Health and Social Sciences, Universidad de Murcia, Murcia, Spain. [Arriola,L] Public Health Division of Gipuzkoa, Instituto BIO-Donostia, Basque Government, Spain. [Wallström,P] Nutrition Epidemiology Research Group, Department of Clinical Sciences, Lund University, Malmö, Sweden. [Tjønneland,A, Olsen,A] Danish Cancer Society Research Center, Copenhagen, Denmark. [Trichopoulou,A, Benetou,V] Department of Hygiene, Epidemiology and Medical Statistics, WHO Collaborating Center for Food and Nutrition Policies, University of Athens Medical School, Athens, Greece.[Trichopoulou,A, Trichopoulos,D] Hellenic Health Foundation, Athens, Greece. [Trichopoulos,D] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. [Tumino,R] Cancer Registry and Histopathology Unit, 'Civic-MP Arezzo' Hospital, ASP Ragusa, Italy. [Agnoli,C] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Sacerdote,C] Unit of Cancer Epidemiology, AO Citta’ della Salute e della Scienza-University of Turin and Center for Cancer Prevention (CPO-Piemonte), Turin, Italy. Human Genetics Foundation (HuGeF), Turin, Italy. [Palli,D] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute—ISPO, Florence, Italy. [Li,K, Kaaks,R] Department of Cancer Epidemiology, German Cancer Research Centre, Heidelberg, Germany. [Peeters,P, Beulens,JW] Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands. [Nunes,L] Department of Statistics, Federal University of Rio Grande do Sul, Porto Alegre, Brazil. [Gunter,M, Norat,T, Norat,E] Department of Epidemiology & Biostatistics, School of Public Health, Imperial College London, London, UK. [Overvad,K] Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark. Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark., Funding This work was supported by the Direction Générale de la Santé (French Ministry of Health) (Grant GR-IARC-2003-09-12-01), by the European Commission (Directorate General for Health and Consumer Affairs) and the International Agency for Research on Cancer. The national cohorts are supported by the Danish Cancer Society (Denmark), the Ligue Contre le Cancer, the Institut Gustave Roussy, the Mutuelle Générale de l’Education Nationale and the Institut National de la Santé et de la Recherche Médicale (France), the Deutsche Krebshilfe, the Deutsches Krebsforschungszentrum, and the Federal Ministry of Education and Research (Germany), the Hellenic Health Foundation, the Stavros Niarchos Foundation and the Hellenic Ministry of Health and Social Solidarity (Greece), the Italian Association for Research on Cancer and the National Research Council (Italy), the Dutch Ministry of Public Health, Welfare and Sports, the Netherlands Cancer Registry, LK, Epidemiology and Data Science, ACS - Diabetes & metabolism, ACS - Heart failure & arrhythmias, and APH - Health Behaviors & Chronic Diseases
Subjects: Gerontology, Male, Time Factors, Etanol, Disease, DISEASE, Cause of Death, Neoplasms, Epidemiology, VDP::Medical disciplines: 700::Health sciences: 800::Health service and health administration research: 806, EPIDEMIOLOGY, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Nutritional Status [Medical Subject Headings], Prospective Studies, Estado Nutricional, Stroke, Nutrition and Dietetics, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, Absolute risk reduction, Geographicals::Geographic Locations::Europe [Medical Subject Headings], Estudios Prospectivos, General Medicine, Diseases::Neoplasms [Medical Subject Headings], Middle Aged, Consumo de bebidas alcohólicas, COMPETING RISKS, Neoplasias, FRACTIONAL POLYNOMIALS, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, RATE ADVANCEMENT PERIODS, Cardiovascular Diseases, Cohort, Female, Europa, Life Sciences & Biomedicine, Adult, medicine.medical_specialty, Alcohol Drinking, MODELS, Cardiology, Risk Assessment, Medicine, General & Internal, Diabetes mellitus, General & Internal Medicine, medicine, Humans, METAANALYSIS, Aged, VDP::Medisinske Fag: 700::Helsefag: 800::Helsetjeneste- og helseadministrasjonsforskning: 806, Science & Technology, Nutrition & Dietetics, business.industry, Research, CONSUMPTION, ADULTS, GLOBAL BURDEN, medicine.disease, Chemicals and Drugs::Organic Chemicals::Alcohols::Ethanol [Medical Subject Headings], Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Drinking Behavior::Alcohol Drinking [Medical Subject Headings], VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business, Demography
Abstract: OBJECTIVES: To investigate the role of factors that modulate the association between alcohol and mortality, and to provide estimates of absolute risk of death.DESIGN: The European Prospective Investigation into Cancer and nutrition (EPIC).SETTING: 23 centres in 10 countries.PARTICIPANTS: 380 395 men and women, free of cancer, diabetes, heart attack or stroke at enrolment, followed up for 12.6 years on average.MAIN OUTCOME MEASURES: 20 453 fatal events, of which 2053 alcohol-related cancers (ARC, including cancers of upper aerodigestive tract, liver, colorectal and female breast), 4187 cardiovascular diseases/coronary heart disease (CVD/CHD), 856 violent deaths and injuries. Lifetime alcohol use was assessed at recruitment.RESULTS: HRs comparing extreme drinkers (≥30 g/day in women and ≥60 g/day in men) to moderate drinkers (0.1-4.9 g/day) were 1.27 (95% CI 1.13 to 1.43) in women and 1.53 (1.39 to 1.68) in men. Strong associations were observed for ARC mortality, in men particularly, and for violent deaths and injuries, in men only. No associations were observed for CVD/CHD mortality among drinkers, whereby HRs were higher in never compared to moderate drinkers. Overall mortality seemed to be more strongly related to beer than wine use, particularly in men. The 10-year risks of overall death for women aged 60 years, drinking more than 30 g/day was 5% and 7%, for never and current smokers, respectively. Corresponding figures in men consuming more than 60 g/day were 11% and 18%, in never and current smokers, respectively. In competing risks analyses, mortality due to CVD/CHD was more pronounced than ARC in men, while CVD/CHD and ARC mortality were of similar magnitude in women.CONCLUSIONS: In this large European cohort, alcohol use was positively associated with overall mortality, ARC and violent death and injuries, but marginally to CVD/CHD. Absolute risks of death observed in EPIC suggest that alcohol is an important determinant of total mortality.
Published: 2014

26. Insulin-like growth factor-i and risk of differentiated thyroid carcinoma in the European prospective investigation into cancer and nutrition

Author: Silvia Franceschi, María Dolores Chirlaque, Marie-Christine Boutron-Ruault, Pagona Lagiou, Kim Overvad, Sylvie Mesrine, Petra H.M. Peeters, Martin Almquist, Ruth C. Travis, Anne Tjønneland, Naomi E. Allen, Laure Dossus, Eva Ardanaz, Salvatore Panico, Dimitrios Trichopoulos, Julie A. Schmidt, Nerea Larrañaga, Rosario Tumino, Elio Riboli, Joakim Hennings, Domenico Palli, Timothy J. Key, Kay-Tee Khaw, Marc J. Gunter, Elisabete Weiderpass, Vittorio Krogh, Sabina Rinaldi, Antonia Trichopoulou, Virginia Menéndez, María José Sánchez, Konstantinos K. Tsilidis, Roberto Zanetti, Eiliv Lund, Rudolf Kaaks, Heiner Boeing, Antonio Agudo, Isabelle Romieu, Annekatrin Lukanova, H. Bas Bueno-de-Mesquita, Nicholas J. Wareham, Maria Sandström, Sarah J. Tipper, Schmidt, Ja, Allen, Ne, Almquist, M, Franceschi, S, Rinaldi, S, Tipper, Sj, Tsilidis, Kk, Weiderpass, E, Overvad, K, Tj?nneland, A, Boutron Ruault, Mc, Dossus, L, Mesrine, S, Kaaks, R, Lukanova, A, Boeing, H, Lagiou, P, Trichopoulos, D, Trichopoulou, A, Palli, D, Krogh, V, Panico, Salvatore, Tumino, R, Zanetti, R, Bueno de Mesquita, Hb, Peeters, Ph, Lund, E, Men?ndez, V, Agudo, A, S?nchez, Mj, Chirlaque, Md, Ardanaz, E, Larra?aga, N, Hennings, J, Sandstr?m, M, Khaw, Kt, Wareham, N, Romieu, I, Gunter, Mj, Riboli, E, Key, Tj, and Travis, Rc
Subjects: Adult, Male, Oncology, medicine.medical_specialty, Epidemiology, media_common.quotation_subject, Article, Thyroid carcinoma, Risk Factors, Internal medicine, medicine, Humans, Prospective Studies, Thyroid Neoplasms, Insulin-Like Growth Factor I, Prospective cohort study, Thyroid cancer, Menstrual cycle, Aged, media_common, business.industry, Case-control study, Cancer, Odds ratio, Middle Aged, medicine.disease, European Prospective Investigation into Cancer and Nutrition, Europe, Nutrition Assessment, Endocrinology, Case-Control Studies, Female, business
Abstract: Background: Little is known about the causes of thyroid cancer, but insulin-like growth factor-I (IGF-I) might play an important role in its development due to its mitogenic and antiapoptotic properties. Methods: This study prospectively investigated the association between serum IGF-I concentrations and risk of differentiated thyroid carcinoma in a case–control study nested within the European Prospective Investigation into Cancer and Nutrition. The 345 incident cases of differentiated thyroid carcinoma were individually matched to 735 controls by study center, sex and age, date, time, and fasting status at blood collection, follow-up duration, and for women menopausal status, use of exogenous hormones, and phase of menstrual cycle at blood collection. Serum IGF-I concentrations were measured by immunoassay, and risk of differentiated thyroid cancer in relation to IGF-I concentration was estimated using conditional logistic regression. Results: There was a positive association between IGF-I concentrations and risk of differentiated thyroid carcinoma: the OR for a doubling in IGF-I concentration was 1.48 (95% confidence interval, 1.06–2.08; Ptrend = 0.02). The positive association with IGF-I was stable over time between blood collection and cancer diagnosis. Conclusion: These findings suggest that IGF-I concentrations may be positively associated with risk of differentiated thyroid carcinoma. Impact: This study provides the first prospective evidence of a potential association between circulating IGF-I concentrations and risk of differentiated thyroid carcinoma and may prompt the further investigations needed to confirm the association. Cancer Epidemiol Biomarkers Prev; 23(6); 976–85. ©2014 AACR.
Published: 2014

27. A genome-wide 'pleiotropy scan' does not identify new susceptibility loci for estrogen receptor negative breast cancer

Author: Walter C. Willett, Peter Kraft, Sara Lindström, Salvatore Panico, Anne Tjønneland, Dieter Flesch-Janys, Carla H. van Gils, Laure Dossus, Elisabete Weiderpass, Saundra S. Buys, David J. Hunter, Stephen J. Chanock, Jenny Chang-Claude, Rudolf Kaaks, Brian E. Henderson, Daniele Campa, Melissa C. Southey, David G. Cox, Federico Canzian, Susan E. Hankinson, Mia M. Gaudet, Laura Baglietto, W. Ryan Diver, Aurelio Barricarte, Afshan Siddiq, Robert N. Hoover, Regina G. Ziegler, Christopher A. Haiman, Christine D. Berg, Konstantinos K. Tsilidis, Loic Le Marchand, Gianluca Severi, Dimitrios Trichopoulos, Malin Sund, Fredrick R. Schumacher, Graham G. Giles, Myrto Barrdahl, Kay-Tee Khaw, Campa, D, Barrdahl, M, Tsilidis, Kk, Severi, G, Diver, Wr, Siddiq, A, Chanock, S, Hoover, Rn, Ziegler, Rg, Berg, Cd, Buys, S, Haiman, Ca, Henderson, Be, Schumacher, Fr, Le Marchand, L, Flesch Janys, D, Lindstr?m, S, Hunter, Dj, Hankinson, Se, Willett, Wc, Kraft, P, Cox, Dg, Khaw, Kt, Tj?nneland, A, Dossus, L, Trichopoulos, D, Panico, Salvatore, van Gils, Ch, Weiderpass, E, Barricarte, A, Sund, M, Gaudet, Mm, Giles, G, Southey, M, Baglietto, L, Chang Claude, J, Kaaks, R, and Canzian, F.
Subjects: Oncology, COMPLEX DISEASES, Databases, Factual, Epidemiology, lcsh:Medicine, Genome-wide association study, Prostate cancer, Breast Tumors, Epidemiology of cancer, Registries, lcsh:Science, Prospective cohort study, RISK, Genetics, Multidisciplinary, Obstetrics and Gynecology, ASSOCIATION, 3. Good health, Multidisciplinary Sciences, Genetic Epidemiology, Science & Technology - Other Topics, Regression Analysis, Medicine, Female, Cancer Epidemiology, TRAITS, Research Article, medicine.medical_specialty, Genotype, General Science & Technology, Breast Neoplasms, Single-nucleotide polymorphism, Polymorphism, Single Nucleotide, Breast cancer, Internal medicine, MD Multidisciplinary, Breast Cancer, Genome-Wide Association Studies, Cancer Genetics, medicine, Humans, Genetic Predisposition to Disease, Biology, Genetic Association Studies, METAANALYSIS, Cancer och onkologi, Science & Technology, Population Biology, VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762, business.industry, lcsh:R, Estrogen Receptor alpha, Case-control study, Cancers and Neoplasms, Cancer, Human Genetics, medicine.disease, VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762, Case-Control Studies, Cancer and Oncology, Genetic Polymorphism, lcsh:Q, business, Population Genetics, Genome-Wide Association Study
Abstract: Approximately 15–30% of all breast cancer tumors are estrogen receptor negative (ER 2 ). Compared with ER-positive (ER + ) disease they have an earlier age at onset and worse prognosis. Despite the vast number of risk variants identified for numerous cancer types, only seven loci have been unambiguously identified for ER-negative breast cancer. With the aim of identifying new susceptibility SNPs for this disease we performed a pleiotropic genome-wide association study (GWAS). We selected 3079 SNPs associated with a human complex trait or disease at genome-wide significance level (P , 5 6 10 2 8 )to perform a secondary analysis of an ER-negative GWAS from the National Cancer Institute’s Breast and Prostate Cancer Cohort Consortium (BPC3), including 1998 cases and 2305 controls from prospective studies. We then tested the top ten associations (i.e. with the lowest P-values) using three additional populations with a total sample size of 3509 ER + cases, 2543 ER 2 cases and 7031 healthy controls. None of the 3079 selected variants in the BPC3 ER-GWAS were significant at the adjusted threshold. 186 variants were associated with ER 2 breast cancer risk at a conventional threshold of P , 0.05, with P- values ranging from 0.049 to 2.3 6 10 2 4 . None of the variants reached statistical significance in the replication phase. In conclusion, this study did not identify any novel susceptibility loci for ER-breast cancer using a ‘‘pleiotropic approach’’.
Published: 2014

28. Combined impact of healthy lifestyle factors on colorectal cancer : a large European cohort study

Author: Domenico Palli, Aurelio Barricarte, José Ramón Quirós, Laureen Dartois, Heather Ward, Salvatore Panico, Isabelle Romieu, Veronika Fedirko, Ulrika Ericson, Kim Overvad, Miren Dorronsoro, Pagona Lagiou, Krasimira Aleksandrova, Rudolf Kaaks, Kay-Tee Khaw, Anne Tjønneland, Elio Riboli, Laure Dossus, Sabina Rinaldi, Ingrid Ljuslinder, Genevieve Buckland, Marc J. Gunter, Petra H.M. Peeters, Vittorio Krogh, Alessio Naccarati, Ingegerd Johansson, Bodil Ohlsson, Peter D. Siersema, Kathryn E. Bradbury, Heiner Boeing, María José Sánchez, Mazda Jenab, Antonia Trichopoulou, H. Bas Bueno-de-Mesquita, Elisabete Weiderpass, Guri Skeie, Kristin Benjaminsen Borch, Tobias Pischon, Sven Knüppel, Teresa Norat, Nicholas J. Wareham, Joyce Kong, Dora Romaguera, Kuanrong Li, Dimitrios Trichopoulos, Rosario Tumino, Marie-Christine Boutron-Ruault, María Dolores Chirlaque, [Aleksandrova,K, Knüppe,S, Boeing,H] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany. [Pischon,T] Molecular Epidemiology Group, Max Delbrueck Center for Molecular Medicine (MDC), Berlin-Buch, Germany. [Jenab,M, Fedirko,V, Rinald,S, Romieu,I, Kong,J] International Agency for Research on Cancer (IARC-WHO), Lyon, France. [Bueno-de-Mesquita,HB] National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands. [Bueno-de-Mesquita,HB, Siersema,PD] Department of Gastroenterology and Hepatology, University Medical Center, Utrecht, the Netherlands. [Bueno-de-Mesquita,HB, Norat,T, Romaguera,D, Peeters,PHM, Gunter,MJ, Ward,HA, Riboli,E] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Fedirko,V] Department of Epidemiology, Rollins School of Public Health, Winship Cancer Institute, Emory University, Atlanta, USA. [Romaguera,D] Instituto de Investigacion Sanitaria de Palma (IdISPa), Hospital Universitario Son Espases, Palma de Mallorca, Spain. CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Santiago de Compostela, Spain. [Boutron-Ruault,M, Dossus,L, Dartois,L] Inserm, Centre for research in Epidemiology and Population Health (CESP), Nutrition, Hormones and Women’s Health team, Villejuif, France. Univ Paris Sud, Villejuif, France. IGR, Villejuif, France. [Kaaks,R, Li,K] Division of Cancer Epidemiology, German Cancer Research Centre, Heidelberg, Germany. [Tjønneland,K] Diet, Genes and Environment Danish Cancer Society Research Center, Copenhagen, Denmark. [Overvad,K] Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus, Denmark. [Quirós,JR] Public Health Directorate, Asturias, Spain. [Buckland,G] Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain. [Sánchez,MJ] Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria de Granada (Granada.ibs), Granada, Spain. [Sánchez,MJ, Chirlaque,M] CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. [Dorronsoro,M] Epidemiology and Health Information, Public Health Division of Gipuzkoa, Basque Regional Health Department, San Sebastian, Spain. [Chirlaque,M] Department of Epidemiology, Murcia Regional Health Authority, Murcia, Spain. [Barricarte,A] Navarre Public Health Institute, Pamplona, Spain. [Khaw,K] Clinical Gerontology Unit, Addenbrooke’s Hospital, University of Cambridge School of Clinical Medicine, Cambridge, UK. [Wareham,NJ] MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, UK. [Bradbury,KE] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK. [Trichopoulou,A] Hellenic Health Foundation, Athens, Greece. [Trichopoulou,A, Lagiou,P, Trichopoulos,D] Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. [Lagiou,P, Trichopoulos,D] Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. [Trichopoulos,D] Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA. [Palli,D] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute – ISPO, Florence, Italy. [Krogh,V] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Tumino,R] Cancer Registry and Histopathology Unit, 'M.P.Arezzo' Hospital, Ragusa, Italy. [Naccarati,A] HuGeF - Human Genetics Foundation – Torino, Molecular and Genetic Epidemiology Unit, Turin, Italy. [Panico,S] Department of clinical and experimental medicine-Federico II University, Naples, Italy. [Peeters,PHM] Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, the Netherland. [Ljuslinder,I] Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden. [Johansson,I] Department of Odontology, Umeå University, Umeå, Sweden. [Ericson,U] Diabetes and Cardiovascular Disease, Genetic Epidemiology, Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden. [Ohlsson,B] Department of Clinical Sciences, Division of Internal Medicine, Skåne University Hospital Malmö, Lund University, Malmö, Sweden. [Weiderpass,E, Skeie,G, Borch,KB] Department of Community Medicine, Faculty of Health Sciences, University of Tromso, The Arctic University of Norway, Tromsø, Norway. [Weiderpass,E] Department of Research, Cancer Registry of Norway, Oslo, Norway. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Samfundet Folkhälsan, Helsinki, Finland., The coordination of the EPIC study is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l¿Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany), Hellenic Health Foundation (Greece), Italian Association for Research on Cancer (AIRC), National Research Council, HuGeF Foundation, Compagnia di San Paolo, Sicily Regional Government, AIRE ONLUS Ragusa and AVIS Ragusa (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF) and Statistics Netherlands (The Netherlands), ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health, Norwegian Research Council, Norwegian Cancer Society, University of Tromso (Norway), Health Research Fund (FIS), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236) and Navarra, ISCIII RETIC (RD06/0020) (Spain), Swedish Cancer Society, Swedish Scientific Council and Regional Government of Skåne and Västerbotten (Sweden), Cancer Research UK, Medical Research Council (United Kingdom)., Aleksandrova, Krasimira, Pischon, Tobia, Jenab, Mazda, Bueno de Mesquita, H. Ba, Fedirko, Veronika, Norat, Teresa, Romaguera, Dora, Knüppel, Sven, Boutron Ruault, Marie Christine, Dossus, Laure, Dartois, Laureen, Kaaks, Rudolf, Li, Kuanrong, Tjønneland, Anne, Overvad, Kim, Quirós, José Ramón, Buckland, Genevieve, Sánchez, María José, Dorronsoro, Miren, Chirlaque, Maria Dolore, Barricarte, Aurelio, Khaw, Kay Tee, Wareham, Nicholas J, Bradbury, Kathryn E, Trichopoulou, Antonia, Lagiou, Pagona, Trichopoulos, Dimitrio, Palli, Domenico, Krogh, Vittorio, Tumino, Rosario, Naccarati, Alessio, Panico, Salvatore, Siersema, Peter D, Peeters, Petra H. M, Ljuslinder, Ingrid, Johansson, Ingegerd, Ericson, Ulrika, Ohlsson, Bodil, Weiderpass, Elisabete, Skeie, Guri, Borch, Kristin Benjaminsen, Rinaldi, Sabina, Romieu, Isabelle, Kong, Joyce, Gunter, Marc J, Ward, Heather A, Riboli, Elio, and Boeing, Heiner
Subjects: Male, consumo de alcohol, Health Behavior, 0302 clinical medicine, estudios prospectivos, European Prospective Investigation into Cancer and, Prospective Studies, estudios de cohortes, mediana edad, PROPORTION, anciano, education.field_of_study, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Motor Activity [Medical Subject Headings], dieta, Incidence, COLON-CANCER, Hazard ratio, lifestyle factors, General Medicine, adulto, 3. Good health, estilo de vida, 030220 oncology & carcinogenesis, Cohort, acrylamide, Dieta, Cohort study, Human, medicine.medical_specialty, Alcohol Drinking, European Continental Ancestry Group, Lifestyles, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Habits::Smoking [Medical Subject Headings], European Prospective Investigation into Cancer and Nutrition (EPIC), Endocrinology and Diabetes, dietary questionnaires, haemoglobin adducts, incidencia, White People, 03 medical and health sciences, Càncer colorectal, population attributable risks, Humans, education, Life Style, METAANALYSIS, Aged, Cancer och onkologi, Science & Technology, Proportional hazards model, VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762, biomarkers, Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [Medical Subject Headings], Psychiatry and Psychology::Behavior and Behavior Mechanisms::Psychology, Social::Life Style [Medical Subject Headings], PREVENTION, Prospective Studie, MYOCARDIAL-INFARCTION, ATTRIBUTABLE RISK, Cardiovascular and Metabolic Diseases, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Cancer and Oncology, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Drinking Behavior::Alcohol Drinking [Medical Subject Headings], RISK-FACTORS, Proportional Hazards Model, grupo de ascendencia continental europea, measurement errors, Gerontology, colorectal cancer, combined impact, modelos de riesgos proporcionales, humanos, Colorectal Neoplasm, Cohort Studies, Risk Factors, Neoplasias colorrectales, Hábito de fumar, 030212 general & internal medicine, Prospective cohort study, conducta sanitaria, Medicine(all), Consumo de alcohol, Public Health, Global Health, Social Medicine and Epidemiology, Middle Aged, European Prospective Investigation into Cancer and Nutrition, Europe, NUTRITION, Female, Colorectal Neoplasms, Life Sciences & Biomedicine, Research Article, Adult, Estils de vida, neoplasias colorrectales, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], Population, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings], smoking, Medicine, General & Internal, General & Internal Medicine, Internal medicine, medicine, factores de riesgo, Proportional Hazards Models, Nutrition (EPIC), RECTAL CANCERS, business.industry, Risk Factor, Diet, VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, PHYSICAL-ACTIVITY, Attributable risk, Cohort Studie, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business
Abstract: Background: Excess body weight, physical activity, smoking, alcohol consumption and certain dietary factors are individually related to colorectal cancer (CRC) risk; however, little is known about their joint effects. The aim of this study was to develop a healthy lifestyle index (HLI) composed of five potentially modifiable lifestyle factors healthy weight, physical activity, non-smoking, limited alcohol consumption and a healthy diet, and to explore the association of this index with CRC incidence using data collected within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods: In the EPIC cohort, a total of 347,237 men and women, 25- to 70-years old, provided dietary and lifestyle information at study baseline (1992 to 2000). Over a median follow-up time of 12 years, 3,759 incident CRC cases were identified. The association between a HLI and CRC risk was evaluated using Cox proportional hazards regression models and population attributable risks (PARs) have been calculated. Results: After accounting for study centre, age, sex and education, compared with 0 or 1 healthy lifestyle factors, the hazard ratio (HR) for CRC was 0.87 (95% confidence interval (CI): 0.44 to 0.77) for two factors, 0.79 (95% CI: 0.70 to 0.89) for three factors, 0.66 (95% CI: 0.58 to 0.75) for four factors and 0.63 (95% CI: 0.54 to 0.74) for five factors; P-trend, The coordination of the EPIC study is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM) (France); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); Hellenic Health Foundation (Greece); Italian Association for Research on Cancer (AIRC), National Research Council, HuGeF Foundation, Compagnia di San Paolo, Sicily Regional Government, AIRE ONLUS Ragusa and AVIS Ragusa (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF) and Statistics Netherlands (The Netherlands); ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health, Norwegian Research Council, Norwegian Cancer Society, University of Tromso (Norway); Health Research Fund (FIS), Regional Governments of Andalucia, Asturias, Basque Country, Murcia (no. 6236) and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Scientific Council and Regional Government of Skane and Vasterbotten (Sweden); Cancer Research UK, Medical Research Council (United Kingdom).
Published: 2014

29. Physical activity, sex steroid, and growth factor concentrations in pre- and post-menopausal women:a cross-sectional study within the EPIC cohort

Author: Heiner Boeing, Malin Sund, Hendrik B. Bueno-de-Mesquita, Nadia Slimani, Antonia Trichopoulou, Elio Riboli, Vassiliki Benetou, Jane Nautrup Østergaard, Isabelle Romieu, Elisabete Weiderpass, Timothy J. Key, Dimitrios Trichopoulos, Augustin Scalbert, Mai-Britt Johansson, Pilar Amiano, Theron Johnson, Noémie Travier, Fulvio Ricceri, Christine M. Friedenreich, José María Huerta, Kim Overvad, Salvatore Panico, Eva Ardanaz, Sabina Rinaldi, Sylvie Mesrine, Marc J. Gunter, Ruth C. Travis, A Lukanova, Giovanna Masala, Vittorio Krogh, Evelyn M. Monninkhof, Esther Molina-Montes, Anne Tjønneland, Nicholas J. Wareham, Matthäus Vigl, A. Olsen, Laure Dossus, Rudolf Kaaks, Carine Biessy, Agnès Fournier, J. R. Quirós, Rosario Tumino, A. M. May, Kay-Tee Khaw, Rinaldi, S, Kaaks, R, Friedenreich, Cm, Key, Tj, Travis, R, Biessy, C, Slimani, N, Overvad, K, Ostergaard, Jn, Tj?nneland, A, Olsen, A, Mesrine, S, Fournier, A, Dossus, L, Lukanova, A, Johnson, T, Boeing, H, Vigl, M, Trichopoulou, A, Benetou, V, Trichopoulos, D, Masala, G, Krogh, V, Tumino, R, Ricceri, F, Panico, Salvatore, Bueno de Mesquita, Hb, Monninkhof, Em, May, Am, Weiderpass, E, Quir?s, Jr, Travier, N, Molina Montes, E, Amiano, P, Huerta, Jm, Ardanaz, E, Sund, M, Johansson, M, Khaw, Kt, Wareham, N, Scalbert, A, Gunter, Mj, Riboli, E, and Romieu, I.
Subjects: Adult, Male, Risk, Cancer Research, medicine.medical_specialty, Cross-sectional study, medicine.medical_treatment, Physical activity, Physiology, Motor Activity, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Neoplasms, Epidemiology, Medicine, Humans, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, Gonadal Steroid Hormones, Aged, 2. Zero hunger, business.industry, Growth factor, Case-control study, Middle Aged, 3. Good health, Europe, Postmenopause, Endocrinology, Cross-Sectional Studies, Oncology, Premenopause, Sex steroid, 030220 oncology & carcinogenesis, Case-Control Studies, Cohort, Intercellular Signaling Peptides and Proteins, Female, sense organs, business
Abstract: Purpose: Increased physical activity (PA) is associated with a reduced risk of several cancers. PA may reduce cancer risk by changing endogenous hormones levels, but relatively little research has focused on this topic. The purpose of this study was to elucidate the relation between PA and endogenous hormone concentrations. Methods: A cross-sectional analysis of 798 pre- and 1,360 post-menopausal women included as controls in case-control studies on endogenous hormones (steroids, progesterone, sex-hormone-binding globulin (SHBG), and growth factors) levels, and cancer risk nested within European Prospective Investigation into Cancer and Nutrition cohort was performed. Multivariate regression analyses were performed to compare geometric mean levels of hormones and SHBG by categories of PA. Results: In pre-menopausal women, active women had 19 % significantly lower concentrations of androstenedione, 14 % lower testosterone, and 20 % lower free testosterone than inactive women, while no differences were observed for estrogens, progesterone, SHBG, and growth factors. In post-menopausal women, active women had 18 % significantly lower estradiol and 20 % lower free estradiol concentrations than inactive women, while no differences were observed for the other hormones and SHBG. More vigorous forms of physical activity were associated with higher insulin-like growth factor-I concentrations. Adjustment for body mass index did not alter the associations. Overall, the percentage of variance in hormone concentrations explained by PA levels was
Published: 2014

30. Biomarker patterns of inflammatory and metabolic pathways are associated with risk of colorectal cancer: results from the European Prospective Investigation into Cancer and Nutrition (EPIC)

Author: Anne Tjønneland, Christina Bamia, Aurelio Barricarte, Laure Dossus, Petra H.M. Peeters, Marc J. Gunter, Sabine Westhpal, Antonia Trichopoulou, Sabina Rinaldi, Ruth C. Travis, Veronika Fedirko, Fränzel J.B. Van Duijnhoven, J. Ramón Quirós, Kay-Tee Khaw, Philippos Orfanos, Rudolf Kaaks, Krasimira Aleksandrova, Richard Palmqvist, Neil Murphy, Esther Molina-Montes, Eric J. Duell, Eugene Jansen, Jytte Halkjær, Nicholas J. Wareham, Tobias Pischon, Mazda Jenab, Antoine Racine, María Dolores Chirlaque, Domenico Palli, Claudia Agnoli, Miren Dorronsoro, Pietro Ferrari, Heiner Boeing, Kim Overvad, Rosario Tumino, Elio Riboli, Ingrid Ljuslinder, Marie-Christine Boutron-Ruault, Salvatore Panico, Annekatrin Lukanova, H. Bas Bueno-de-Mesquita, Isabelle Romieu, Paolo Vineis, Aleksandrova, K, Jenab, M, Bueno de Mesquita, Hb, Fedirko, V, Kaaks, R, Lukanova, A, van Duijnhoven, Fj, Jansen, E, Rinaldi, S, Romieu, I, Ferrari, P, Murphy, N, Gunter, Mj, Riboli, E, Westhpal, S, Overvad, K, Tj?nneland, A, Halkj?r, J, Boutron Ruault, Mc, Dossus, L, Racine, A, Trichopoulou, A, Bamia, C, Orfanos, P, Agnoli, C, Palli, D, Panico, Salvatore, Tumino, R, Vineis, P, Peeters, Ph, Duell, Ej, Molina Montes, E, Quir?s, Jr, Dorronsoro, M, Chirlaque, Md, Barricarte, A, Ljuslinder, I, Palmqvist, R, Travis, Rc, Khaw, Kt, Wareham, N, Pischon, T, and Boeing, H.
Subjects: Oncology, Male, Nutrition and Disease, multiple imputation, Epidemiology, hdl-cholesterol, Rate ratio, adipose-tissue, Body Mass Index, chemistry.chemical_compound, c-reactive protein, Risk Factors, Voeding en Ziekte, plasma adiponectin, oxidative stress, Prospective Studies, Prospective cohort study, Incidence, density-lipoprotein cholesterol, Middle Aged, Prognosis, European Prospective Investigation into Cancer and Nutrition, Europe, C-Reactive Protein, Biomarker (medicine), Female, Colorectal Neoplasms, Metabolic Networks and Pathways, medicine.medical_specialty, binding-proteins, insulin-resistance, soluble leptin receptor, Adipokines, Internal medicine, medicine, Biomarkers, Tumor, Humans, Triglycerides, VLAG, Aged, Glycated Hemoglobin, Inflammation, Leptin receptor, Adiponectin, business.industry, Case-control study, Endocrinology, Logistic Models, chemistry, Socioeconomic Factors, Case-Control Studies, Glycated hemoglobin, business
Abstract: A number of biomarkers of inflammatory and metabolic pathways are individually related to higher risk of colorectal cancer (CRC); however, the association between biomarker patterns and CRC incidence has not been previously evaluated. Our study investigates the association of biomarker patterns with CRC in a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC). During median follow-up time of 7.0 (3.7-9.4) years, 1,260 incident CRC cases occurred and were matched to 1,260 controls using risk-set sampling. Pre-diagnostic measurements of C-peptide, glycated hemoglobin, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), C-reactive protein (CRP), reactive oxygen metabolites (ROM), insulin-like growth factor 1, adiponectin, leptin and soluble leptin receptor (sOB-R) were used to derive biomarker patterns from principal component analysis (PCA). The relation with CRC incidence was assessed using conditional logistic regression models. We identified four biomarker patterns 'HDL-C/Adiponectin fractions', 'ROM/CRP', 'TG/C-peptide' and 'leptin/sOB-R' to explain 60% of the overall biomarker variance. In multi-variable-adjusted logistic regression, the 'HDL-C/Adiponectin fractions', 'ROM/CRP' and 'leptin/sOB-R' patterns were associated with CRC risk [for the highest quartile vs the lowest, incidence rate ratio (IRR) = 0.69, 95% CI 0.51-0.93, P-trend = 0.01; IRR = 1.70, 95% CI 1.30-2.23, P-trend = 0.002; and IRR = 0.79, 95% CI 0.58-1.07; P-trend = 0.05, respectively]. In contrast, the 'TG/C-peptide' pattern was not associated with CRC risk (IRR = 0.75, 95% CI 0.56-1.00, P-trend = 0.24). After cases within the first 2 follow-up years were excluded, the 'ROM/CRP' pattern was no longer associated with CRC risk, suggesting potential influence of preclinical disease on these associations. By application of PCA, the study identified 'HDL-C/Adiponectin fractions', 'ROM/CRP' and 'leptin/sOB-R' as biomarker patterns representing potentially important pathways for CRC development. © Springer Science+Business Media 2014.
Published: 2013

31. N-acetyltransferase 2 phenotype, occupation, and bladder cancer risk: results from the EPIC cohort

Author: Mattias Johansson, Pietro Ferrari, Salvatore Panico, Kim Overvad, Hans-Peter Rihs, Timothy J. Key, Miren Dorronsoro, Domenico Palli, Martine M. Ros, Paolo Vineis, José Ramón Quirós, Jenny Chang-Claude, Roy Ehrnström, H. Bas Bueno-de-Mesquita, Sylvia Rabstein, Anne Tjønneland, Aurelio Barricarte, Carlos González, Elio Riboli, Laure Dossus, Katarzyna Gawrych, Kay-Tee Khaw, Isabelle Romieu, Börje Ljungberg, Marie-Christine Boutron-Ruault, Steffen Weikert, María José Sánchez, Norman Klopp, Françoise Clavel-Chapelon, Rudolph Kaaks, Sabina Sieri, Carmen Navarro, Dimitrios Trichopoulos, Hui Ding, Jürgen Angerer, Nicholas J. Wareham, Swaantje Casjens, Nina Roswall, David Ulmert, Heiner Boeing, Beate Pesch, Thomas Brüning, Rosario Tumino, Tobias Weiss, Thomas Illig, Pesch, B, Gawrych, K, Rabstein, S, Weiss, T, Casjens, S, Rihs, Hp, Ding, H, Angerer, J, Illig, T, Klopp, N, Bueno de Mesquita, B, Ros, Mm, Kaaks, R, Chang Claude, J, Roswall, N, Tj?nneland, A, Overvad, K, Clavel Chapelon, F, Boutron Ruault, Mc, Dossus, L, Boeing, H, Weikert, S, Trichopoulos, D, Palli, D, Sieri, S, Tumino, R, Panico, Salvatore, Quir?s, Jr, Gonz?lez, C, S?nchez, Mj, Dorronsoro, M, Navarro, C, Barricarte, A, Ljungberg, B, Johansson, M, Ulmert, D, Ehrnstr?m, R, Khaw, Kt, Wareham, N, Key, Tj, Ferrari, P, Romieu, I, Riboli, E, Br?ning, T, and Vineis, P.
Subjects: Oncology, Adult, Male, medicine.medical_specialty, Pathology, Genotype, Epidemiology, Arylamine N-Acetyltransferase, Polymorphism, Single Nucleotide, Young Adult, Risk Factors, Internal medicine, Occupational Exposure, medicine, Humans, Amines, Polycyclic Aromatic Hydrocarbons, Genotyping, Genetic testing, Aged, Bladder cancer, medicine.diagnostic_test, business.industry, Acetylation, Middle Aged, medicine.disease, Confidence interval, European Prospective Investigation into Cancer and Nutrition, Phenotype, Urinary Bladder Neoplasms, Case-Control Studies, Cohort, Female, business, Cohort study
Abstract: Background: An association between N-acetyltransferase 2 (NAT2) slow acetylation and bladder cancer has been consistently observed in epidemiologic studies. However, evidence has been mainly derived from case–control studies and was sparse from cohort studies. We evaluated the association between NAT2 slow acetylation and bladder cancer in a case–control study nested in the European Prospective Investigation into Cancer and Nutrition. Methods: Exposure to aromatic amines and polycyclic aromatic hydrocarbons (PAH) could be assessed for 754 cases and 833 controls for whom occupational information was documented. A semiquantitative job-exposure matrix was applied to at-risk occupations to estimate the exposure as low, medium, or high based on tertiles of the distribution of the exposure score in controls. Using a comprehensive genotyping, NAT2 acetylation status could be categorized from 6-single-nucleotide polymorphism genotypes as slow or fast in 607 cases and 695 controls with DNA from archived blood samples. Results: Occupational exposure to aromatic amines and PAH was associated with an increased bladder cancer risk [upper tertile of the distribution of the exposure score: OR = 1.37; 95% confidence interval (CI), 1.02–1.84, and OR = 1.50; 95% CI, 1.09–2.05, respectively]. NAT2 slow acetylation did not modify these risk estimates and was not itself associated with bladder cancer risk (OR = 1.02; 95% CI, 0.81–1.29). Conclusions: These findings confirm established or suspected occupational risk factors but not the anticipated role of NAT2 slow acetylation in bladder cancer. No interaction was detected between NAT2 and any exposure of interest, including smoking. Impact: Genetic testing for NAT2 would be inappropriate in occupational settings. Cancer Epidemiol Biomarkers Prev; 22(11); 2055–65. ©2013 AACR.
Published: 2013

32. Menstrual and reproductive factors in women, genetic variation in CYP17A1, and pancreatic cancer risk in the european prospective investigation into cancer and nutrition (EPIC) cohort

Author: José María Huerta, Elio Riboli, Annekatrin Lukanova, H. Bas Bueno-de-Mesquita, Leila Lujan-Barroso, Maria Luisa Redondo, Madlen Schuetze, Eric J. Duell, Eirini Fragogeorgi, Nicholas J. Wareham, Petra H.M. Peeters, Veronika Fedirko, Peter D. Siersema, Inger T. Gram, Dorthe Johansen, Vittorio Krogh, Aurelio Barricarte, Eleni Oikonomou, Nina Roswall, Ruth C. Travis, Mazda Jenab, Kim Overvad, Anne Tjønneland, Heiner Boeing, Dominique S. Michaud, Malin Sund, Laure Dossus, Eiliv Lund, Kay-Tee Khaw, Giovanna Masala, Weimin Ye, Miren Dorronsoro, Federico Canzian, Björn Lindkvist, Marie-Christine Boutron-Ruault, Françoise Clavel-Chapelon, Salvatore Panico, Noémie Travier, Fulvio Ricceri, Naomi E. Allen, Rosario Tumino, Antonia Trichopoulou, Elisabete Weiderpass, Esther Molina-Montes, Duell, Ej, Travier, N, Lujan Barroso, L, Dossus, L, Boutron Ruault, Mc, Clavel Chapelon, F, Tumino, R, Masala, G, Krogh, V, Panico, Salvatore, Ricceri, F, Redondo, Ml, Dorronsoro, M, Molina Montes, E, Huerta, Jm, Barricarte, A, Khaw, Kt, Wareham, Nj, Allen, Ne, Travis, R, Siersema, Pd, Peeters, Ph, Trichopoulou, A, Fragogeorgi, E, Oikonomou, E, Boeing, H, Schuetze, M, Canzian, F, Lukanova, A, Tj?nneland, A, Roswall, N, Overvad, K, Weiderpass, E, Gram, It, Lund, E, Lindkvist, B, Johansen, D, Ye, W, Sund, M, Fedirko, V, Jenab, M, Michaud, D, Riboli, E, and Bueno de Mesquita, Hb
Subjects: Oncology, Adult, Male, Cancer Research, medicine.medical_specialty, Genotype, Single-nucleotide polymorphism, Genome-wide association study, Adenocarcinoma, Polymorphism, Single Nucleotide, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Pancreatic cancer, Internal medicine, medicine, Humans, Prospective Studies, Prospective cohort study, Reproductive History, 030304 developmental biology, Neoplasm Staging, Gynecology, 0303 health sciences, business.industry, Steroid 17-alpha-Hydroxylase, Middle Aged, medicine.disease, Prognosis, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Menstruation, Pancreatic Neoplasms, Haplotypes, 030220 oncology & carcinogenesis, Case-Control Studies, Cohort, Menarche, Female, business, Cohort study, Follow-Up Studies
Abstract: Menstrual and reproductive factors and exogenous hormone use have been investigated as pancreatic cancer risk factors in case-control and cohort studies, but results have been inconsistent. We conducted a prospective examination of menstrual and reproductive factors, exogenous hormone use and pancreatic cancer risk (based on 304 cases) in 328,610 women from the EPIC cohort. Then, in a case-control study nested within the EPIC cohort, we examined 12 single nucleotide polymorphisms (SNPs) in CYP17A1 (an essential gene in sex steroid metabolism) for association with pancreatic cancer in women and men (324 cases and 353 controls). Of all factors analyzed, only younger age at menarche (
Published: 2013

33. Comprehensive analysis of common genetic variation in 61 genes related to steroid hormone and insulin-like growth factor-I metabolism and breast cancer risk in the NCI breast and prostate cancer cohort consortium

Author: Anika Hüsing, Lars Beckmann, Kim Overvad, V. Wendy Setiawan, Miren Dorronsoro, Daniel O. Stram, Salvatore Panico, Laurence N. Kolonel, Julie E. Buring, Stephen J. Chanock, Saundra S. Buys, Françoise Clavel-Chapelon, Brian E. Henderson, David G. Cox, Elio Riboli, Hélène Blanché, Rosario Tumino, Meredith Yeager, John Oliver L. DeLancey, Federico Canzian, Peter Kraft, Gilles Thomas, Petra H.M. Peeters, Michael J. Thun, David J. Hunter, Claudine Isaacs, Regina G. Ziegler, Rudolf Kaaks, W. Ryan Diver, Anne Tjønneland, Eugenia E. Calle, Susan E. Hankinson, Sheila Bingham, Göran Hallmans, Laure Dossus, Christopher A. Haiman, Michael Pollak, Robert N. Hoover, Eiliv Lund, Dimitrios Trichopoulos, Christine D. Berg, Loic Le Marchand, Aurelio Barricarte, Heather Spencer Feigelson, Kay-Tee Khaw, Canzian, F, Cox, Dg, Setiawan, Vw, Stram, Do, Ziegler, Rg, Dossus, L, Beckmann, L, Blanché, H, Barricarte, A, Berg, Cd, Bingham, S, Buring, J, Buys, S, Calle, Ee, Chanock, Sj, Clavel Chapelon, F, Delancey, Jo, Diver, Wr, Dorronsoro, M, Haiman, Ca, Hallmans, G, Hankinson, Se, Hunter, Dj, Hüsing, A, Isaacs, C, Khaw, Kt, Kolonel, Ln, Kraft, P, Le Marchand, L, Lund, E, Overvad, K, Panico, Salvatore, Peeters, Ph, Pollak, M, Thun, Mj, Tjønneland, A, Trichopoulos, D, Tumino, R, Yeager, M, Hoover, Rn, Riboli, E, Thomas, G, Henderson, Be, Kaaks, R, and Feigelson, Hs
Subjects: Male, Quality Control, Oncology, medicine.medical_specialty, medicine.drug_class, medicine.medical_treatment, Breast Neoplasms, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Cohort Studies, Prostate cancer, Breast cancer, Risk Factors, Internal medicine, Genetics, medicine, Humans, Genetic Predisposition to Disease, Insulin-Like Growth Factor I, Gonadal Steroid Hormones, Molecular Biology, Genetics (clinical), Aged, Association Studies Articles, Prostatic Neoplasms, Cancer, General Medicine, Middle Aged, medicine.disease, National Cancer Institute (U.S.), United States, Steroid hormone, Endocrinology, Haplotypes, Estrogen, Female, Breast disease, Steroid hormone metabolism
Abstract: There is extensive evidence that increases in blood and tissue concentrations of steroid hormones and of insulin-like growth factor I (IGF-I) are associated with breast cancer risk. However, studies of common variation in genes involved in steroid hormone and IGF-I metabolism have yet to provide convincing evidence that such variants predict breast cancer risk. The Breast and Prostate Cancer Cohort Consortium (BPC3) is a collaboration of large US and European cohorts. We genotyped 1416 tagging single nucleotide polymorphisms (SNPs) in 37 steroid hormone metabolism genes and 24 IGF-I pathway genes in 6292 cases of breast cancer and 8135 controls, mostly Caucasian, postmenopausal women from the BPC3. We also imputed 3921 additional SNPs in the regions of interest. None of the SNPs tested was significantly associated with breast cancer risk, after correction for multiple comparisons. The results remained null when cases and controls were stratified by age at diagnosis/recruitment, advanced or nonadvanced disease, body mass index, with or without in situ cases; or restricted to Caucasians. Among 770 estrogen receptor-negative cases, an SNP located 3' of growth hormone receptor (GHR) was marginally associated with increased risk after correction for multiple testing (P(trend) = 1.5 × 10(-4)). We found no significant overall associations between breast cancer and common germline variation in 61 genes involved in steroid hormone and IGF-I metabolism in this large, comprehensive study. Although previous studies have shown that variations in these genes can influence endogenous hormone levels, the magnitude of the effect of single SNPs does not appear to be sufficient to alter breast cancer risk.
Published: 2010

34. The association between diet and serum concentrations of IGF-I, IGFBP-1, IGFBP-2, and IGFBP-3 in the European Prospective Investigation into Cancer and Nutrition

Author: Paula Jakszyn, Marie-Christine Boutron-Ruault, Inger T. Gram, Carlotta Sacerdote, Sheila Bingham, H. Bas Bueno-de-Mesquita, Antonia Trichopoulou, Françoise Clavel-Chapelon, Teresa Norat, Nerea Larrañaga, Valentina Gallo, Aurelio Barricarte, Carla H. van Gils, Kay-Tee Khaw, Timothy J. Key, Salvatore Panico, Andrew W. Roddam, Guri Skeie, Rudolf Kaaks, María J. Tormo, Dimitrios Trichopoulos, Blandine de Lauzon, Naomi E. Allen, Esther Molina-Montes, Rosario Tumino, Anne Tjønneland, Eiliv Lund, Laudina Rodríguez, Vardis Dilis, Franco Berrino, Petra H.M. Peeters, Laure Dossus, Jutte Halkjær, Sabina Rinaldi, Janine Kröger, Francesca L. Crowe, Elio Riboli, Alina Vrieling, Kim Overvad, Henning Grønbæk, Paul N. Appleby, Domenico Palli, Heiner Boeing, Nadia Slimani, Crowe, Fl, Key, Tj, Allen, Ne, Appleby, Pn, Roddam, A, Overvad, K, Grønbaek, H, Tjønneland, A, Halkjaer, J, Dossus, L, Boeing, H, Kröger, J, Trichopoulou, A, Dilis, V, Trichopoulos, D, Boutron Ruault, Mc, De Lauzon, B, Clavel Chapelon, F, Palli, D, Berrino, F, Panico, Salvatore, Tumino, R, Sacerdote, C, Bueno de Mesquita, Hb, Vrieling, A, van Gils, Ch, Peeters, Ph, Gram, It, Skeie, G, Lund, E, Rodríguez, L, Jakszyn, P, Molina Montes, E, Tormo, Mj, Barricarte, A, Larrañaga, N, Khaw, Kt, Bingham, S, Rinaldi, S, Slimani, N, Norat, T, Gallo, V, Riboli, E, and Kaaks, R.
Subjects: Male, Questionnaires, medicine.medical_specialty, Epidemiology, medicine.medical_treatment, chemistry.chemical_element, Calcium, Body Mass Index, Insulin-like growth factor, Blood serum, Sex Factors, Surveys and Questionnaires, Internal medicine, medicine, Humans, Prospective Studies, Insulin-Like Growth Factor I, biology, business.industry, Age Factors, Cancer, Proteins, Serum concentration, Middle Aged, medicine.disease, European Prospective Investigation into Cancer and Nutrition, Diet, Calcium, Dietary, Europe, Insulin-Like Growth Factor Binding Protein 1, Insulin-Like Growth Factor Binding Protein 2, Endocrinology, Cross-Sectional Studies, Insulin-Like Growth Factor Binding Protein 3, Oncology, chemistry, Insulin-like growth factor 2, biology.protein, Linear Models, Female, business, Energy Intake, Body mass index
Abstract: Circulating concentrations of insulin-like growth factor I (IGF-I) and IGF binding proteins (IGFBP) have been associated with the risk of several types of cancer. Dietary correlates of IGF-I and IGFBPs are not yet well established. The objective of this study was to assess the association between dietary intake and serum concentrations of IGF-I, IGFBP-1, IGFBP-2, and IGFBP-3 in a cross-sectional analysis of 4,731 men and women taking part in the European Prospective Investigation into Cancer and Nutrition. Diet was assessed using country-specific validated dietary questionnaires. Serum concentrations of IGF-I, IGFBP-1, IGFBP-2 and IGFBP-3 were measured, and the associations between diet and IGF-I and IGFBPs were assessed using multiple linear regression adjusting for sex, age, body mass index, smoking status, and alcohol and energy intake. Each 1 SD increment increase in total and dairy protein and calcium intake was associated with an increase in IGF-I concentration of 2.5%, 2.4%, and 3.3%, respectively (P for trend
Published: 2009

35. Vitamin D receptor polymorphisms and breast cancer risk: results from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium

Author: Barbara Saltzman, H. Bas Bueno-de-Mesquita, Stephen J. Chanock, Walter C. Willett, Michael J. Thun, Jakob Linseisen, Kim Overvad, Dimitrios Trichopoulos, Jeffrey Yuenger, Julie E. Buring, Eugenia E. Calle, Susan E. Hankinson, Sheila Bingham, Heather Spencer Feigelson, Laurie Burdette, Robert N. Hoover, Laurence N. Kolonel, Laure Dossus, Françoise Clavel-Chapelon, Marjorie L. McCullough, Mark P. Purdue, Anika Hüsing, Christopher A. Haiman, Regina G. Ziegler, Christine D. Berg, Goran Bergland, Salvatore Panico, Catherine A. McCarty, Rudolph Kaaks, Aurelio Barricarte, David J. Hunter, Daniel O. Stram, Magritt Brustad, Peter Kraft, James D. McKay, Loic Le Marchand, Victoria L. Stevens, David G. Cox, Elio Riboli, Mckay, Jd, Mccullough, Ml, Ziegler, Rg, Kraft, P, Saltzman, B, Riboli, E, Barricarte, A, Berg, Cd, Bergland, G, Bingham, S, Brustad, M, Bueno de Mesquita, Hb, Burdette, L, Buring, J, Calle, Ee, Chanock, Sj, Clavel Chapelon, F, Cox, Dg, Dossus, L, Feigelson, H, Haiman, Ca, Hankinson, Se, Hoover, Rn, Hunter, Dj, Husing, A, Kaaks, R, Kolonel, Ln, Le Marchand, L, Linseisen, J, Mccarty, Ca, Overvad, K, Panico, Salvatore, Purdue, Mp, Stram, Do, Stevens, Vl, Trichopoulos, D, Willett, Wc, Yuenger, J, and Thun, M. J.
Subjects: Oncology, Adult, Risk, medicine.medical_specialty, Genotype, Epidemiology, Breast Neoplasms, Calcitriol receptor, Polymorphism, Single Nucleotide, Linkage Disequilibrium, Prostate cancer, Breast cancer, Internal medicine, medicine, Humans, Prospective Studies, Prospective cohort study, Aged, business.industry, Cancer, Odds ratio, Middle Aged, medicine.disease, Endocrinology, Logistic Models, Case-Control Studies, Receptors, Calcitriol, Female, Breast disease, business
Abstract: Background: Vitamin D is hypothesized to lower the risk of breast cancer by inhibiting cell proliferation via the nuclear vitamin D receptor (VDR). Two common single nucleotide polymorphisms (SNP) in the VDR gene (VDR), rs1544410 (BsmI), and rs2228570 (FokI), have been inconsistently associated with breast cancer risk. Increased risk has been reported for the FokI ff genotype, which encodes a less transcriptionally active isoform of VDR, and reduced risk has been reported for the BsmI BB genotype, a SNP in strong linkage disequilibrium with a 3′-untranslated region, which may influence VDR mRNA stability. Methods: We pooled data from 6 prospective studies in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium to examine associations between these SNPs and breast cancer among >6,300 cases and 8,100 controls for each SNP using conditional logistic regression. Results: The odds ratio (OR) for the rs2228570 (FokI) ff versus FF genotype in the overall population was statistically significantly elevated [OR, 1.16; 95% confidence interval (95% CI), 1.04-1.28] but was weaker once data from the cohort with previously published positive findings were removed (OR, 1.10; 95% CI, 0.98-1.24). No association was noted between rs1544410 (BsmI) BB and breast cancer risk overall (OR, 0.98; 95% CI, 0.89-1.09), but the BB genotype was associated with a significantly lower risk of advanced breast cancer (OR, 0.74; 95% CI, 0.60-0.92). Conclusions: Although the evidence for independent contributions of these variants to breast cancer susceptibility remains equivocal, future large studies should integrate genetic variation in VDR with biomarkers of vitamin D status. (Cancer Epidemiol Biomarkers Prev 2009;18(1):297–305)
Published: 2009

36. Endogenous sex hormones and endometrial cancer risk in women in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Author: Rudolf Kaaks, Domenico Palli, Jenny Chang-Claude, Marie-Christine Boutron-Ruault, Françoise Clavel-Chapelon, J. Ramón Quirós, Eva Ardanaz, Elio Riboli, Annekatrin Lukanova, Kim Overvad, Anne E. Cust, Heiner Boeing, Dimitiros Trichopoulos, Guillem Pera, Anja Olsen, H. Bas Bueno-de-Mesquita, Salvatore Panico, Eva Lundin, Mandy Schulz, María José Tormo, Naomi E. Allen, Franco Berrino, Kay-Tee Khaw, Timothy J. Key, Petra H. Lahmann, Rosario Tumino, Anne Tjønneland, Androniki Naska, Laure Dossus, Nerea Larrañaga, Petra H.M. Peeters, Sheila Bingham, Antonia Trichopoulou, Sabina Rinaldi, María José Sánchez, Jakob Linseisen, N. Charlotte Onland-Moret, Allen, Ne, Key, Tj, Dossus, L, Rinaldi, S, Cust, A, Lukanova, A, Peeters, Ph, Onland Moret, Nc, Lahmann, Ph, Berrino, F, Panico, Salvatore, Larrañaga, N, Pera, G, Tormo, Mj, Sánchez, Mj, Ramón Quirós, J, Ardanaz, E, Tjønneland, A, Olsen, A, Chang Claude, J, Linseisen, J, Schulz, M, Boeing, H, Lundin, E, Palli, D, Overvad, K, Clavel Chapelon, F, Boutron Ruault, Mc, Bingham, S, Khaw, Kt, Bueno de Mesquita, Hb, Trichopoulou, A, Trichopoulos, D, Naska, A, Tumino, R, Riboli, E, and Kaaks, R.
Subjects: Cancer Research, Endocrinology, Diabetes and Metabolism, Body Mass Index, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Sex hormone-binding globulin, Risk Factors, Sex Hormone-Binding Globulin, Odds Ratio, Medicine, Testosterone, Prospective Studies, Gonadal Steroid Hormones, media_common, 0303 health sciences, Estradiol, biology, Dehydroepiandrosterone Sulfate, Incidence, Middle Aged, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, Postmenopause, Oncology, 030220 oncology & carcinogenesis, Female, Adult, medicine.medical_specialty, Estrone, media_common.quotation_subject, 03 medical and health sciences, Dehydroepiandrosterone sulfate, Humans, ddc:610, Menstrual cycle, Aged, 030304 developmental biology, Gynecology, business.industry, Endometrial cancer, Androstenedione, Odds ratio, medicine.disease, Endometrial Neoplasms, Premenopause, chemistry, biology.protein, Regular papers, business
Abstract: Udgivelsesdato: 2008-Jun Epidemiological data show that reproductive and hormonal factors are involved in the etiology of endometrial cancer, but there is little data on the association with endogenous sex hormone levels. We analyzed the association between prediagnostic serum concentrations of sex steroids and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition using a nested case-control design of 247 incident endometrial cancer cases and 481 controls, matched on center, menopausal status, age, variables relating to blood collection, and, for premenopausal women, phase of menstrual cycle. Using conditional regression analysis, endometrial cancer risk among postmenopausal women was positively associated with increasing levels of total testosterone, free testosterone, estrone, total estradiol, and free estradiol. The odds ratios (ORs) for the highest versus lowest tertile were 2.66 (95% confidence interval (CI) 1.50-4.72; P=0.002 for a continuous linear trend) for estrone, 2.07 (95% CI 1.20-3.60; P=0.001) for estradiol, and 1.66 (95% CI 0.98-2.82; P=0.001) for free estradiol. For total and free testosterone, ORs for the highest versus lowest tertile were 1.44 (95% CI 0.88-2.36; P=0.05) and 2.05 (95% CI 1.23-3.42; P=0.005) respectively. Androstenedione and dehydroepiandrosterone sulfate were not associated with risk. Sex hormone-binding globulin was significantly inversely associated with risk (OR for the highest versus lowest tertile was 0.57, 95% CI 0.34-0.95; P=0.004). In premenopausal women, serum sex hormone concentrations were not clearly associated with endometrial cancer risk, but numbers were too small to draw firm conclusions. In conclusion, relatively high blood concentrations of estrogens and free testosterone are associated with an increased endometrial cancer risk in postmenopausal women.
Published: 2008

37. Haplotype-based analysis of common variation in the acetyl-coA carboxylase alpha gene and breast cancer risk: a case-control study nested within the European Prospective Investigation into Cancer and Nutrition

Author: Eva Ardanaz, James McKay, Guillem Pera, Véronique Chajès, Carla H. van Gils, Miren Dorronsoro, H. Bas Bueno-de-Mesquita, Rudolf Kaaks, Federico Canzian, Petra H.M. Peeters, Göran Berglund, Lydie Gioia, Sean V. Tavtigian, Heiner Boeing, Göran Hallmans, Carine Biessy, Carmen Martinez Garcia, Anja Olsen, Sheila Bingham, Antonia Trichopoulou, Olga M. Sinilnikova, Eiliv Lund, Naomi E. Allen, Franco Berrino, Per Lenner, Françoise Clavel-Chapelon, Stephan Dahm, Majken K. Jensen, Jakob Linseisen, Deepika DeSilva, Elio Riboli, José Ramón Quirós, Jonas Manjer, Kim Overvad, Anne Tjønneland, Laure Dossus, Dimitrios Trichopoulos, Rosario Tumino, Virginie Joulin, Paolo Vineis, Kay-Tee Khaw, Salvatore Panico, Gilbert M. Lenoir, Domenico Palli, Stéphanie Monnier, Jenny Chang-Claude, María José Tormo, Maria Koliva, David J. Hughes, Catherine Boillot, Timothy J. Key, Sinilnikova, Om, Mckay, Jd, Tavtigian, Sv, Canzian, F, Desilva, D, Biessy, C, Monnier, S, Dossus, L, Boillot, C, Gioia, L, Hughes, Dj, Jensen, Mk, Overvad, K, Tjonneland, A, Olsen, A, CLAVEL CHAPELON, F, Chajes, V, Joulin, V, Linseisen, J, CHANG CLAUDE, J, Boeing, H, Dahm, S, Trichopoulou, A, Trichopoulos, D, Koliva, M, Khaw, Kt, Bingham, S, Allen, Ne, Key, T, Palli, D, Panico, Salvatore, Berrino, F, Tumino, R, Vineis, P, BUENO DE MESQUITA, Hb, Peeters, Ph, VAN GILS, Ch, Lund, E, Pera, G, Quiros, Jr, Dorronsoro, M, MARTINEZ GARCIA, C, Tormo, Mj, Ardanaz, E, Hallmans, G, Lenner, P, Berglund, G, Manjer, J, Riboli, E, Lenoir, Gm, and Kaaks, R.
Subjects: Oncology, Adult, medicine.medical_specialty, Genotype, Epidemiology, Breast Neoplasms, Biology, Breast cancer, Gene Frequency, Polymorphism (computer science), Risk Factors, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, Risk factor, Alleles, Aged, Genetics, Chi-Square Distribution, Haplotype, Acetyl-CoA carboxylase, Case-control study, Genetic Variation, Middle Aged, medicine.disease, European Prospective Investigation into Cancer and Nutrition, Europe, Logistic Models, Haplotypes, Case-Control Studies, Female, Acetyl-CoA Carboxylase
Abstract: A key fatty acid synthesis enzyme, acetyl-CoA carboxylase α (ACC-α), has been shown to be highly expressed in human breast cancer and other tumor types and also to specifically interact with the protein coded by one of two major breast cancer susceptibility genes BRCA1. We used a comprehensive haplotype analysis to examine the contribution of the ACC-α common genetic variation (allele frequency >5%) to breast cancer in a case-control study (1,588 cases/2,600 controls) nested within the European Prospective Investigation into Cancer and Nutrition. We identified 21 haplotype-tagging polymorphisms efficiently capturing common variation within 325 kb of ACC-α and surrounding sequences using genotype data from the HapMap project and our resequencing data. We found an effect on overall risk of breast cancer in homozygous carriers of one common haplotype [odds ratio (OR), 1.74; 95% confidence interval (95% CI), 1.03-2.94]. When the data were subdivided by menopausal status, we found statistical evidence of heterogeneity for two other common haplotypes (P value for heterogeneity = 0.016 and 0.045). In premenopausal women, the carriers of these haplotypes, compared with noncarriers, had an altered risk of breast cancer (OR, 0.70; 95% CI, 0.53-0.92 and OR, 1.35; 95% CI, 1.04-1.76). These findings were not significant after adjustment for multiple testing and therefore should be considered as preliminary and evaluated in larger independent studies. However, they suggest a possible role of the ACC-α common sequence variants in susceptibility to breast cancer and encourage studies of other genes involved in fatty acid synthesis. (Cancer Epidemiol Biomarkers Prev 2007;16(3):409–15)
Published: 2007

38. Genetic variation at the CYP19A1 locus predicts circulating estrogen levels but not breast cancer risk in postmenopausal women

Author: Eugenia E. Calle, Susan E. Hankinson, Noël P. Burtt, Stephen J. Chanock, Brian E. Henderson, David G. Cox, Christopher A. Haiman, Elio Riboli, Loic Le Marchand, Petra H.M. Peeters, Rudolf Kaaks, Julie E. Buring, Anne Tjønneland, Demetrius Albanes, Laure Dossus, Per Lenner, Sholom Wacholder, Françoise Clavel-Chapelon, Ruth C. Travis, Robert N. Hoover, Eiliv Lund, Gilles Thomas, David J. Hunter, Dimitrios Trichopoulos, Michael J. Thun, Eva Ardanaz, Heather Spencer Feigelson, V. Wendy Setiawan, Laurence N. Kolonel, Graham A. Colditz, Joel N. Hirschhorn, Heiner Boeing, Richard B. Hayes, Salvatore Panico, Malcolm Cecil Pike, Regina G. Ziegler, Alison M. Dunning, David Altshuler, Daniel O. Stram, Haiman, Ca, Dossus, L, Setiawan, Vw, Stram, Do, Dunning, Am, Thomas, G, Thun, Mj, Albanes, D, Altshuler, D, Ardanaz, E, Boeing, H, Buring, J, Burtt, N, Calle, Ee, Chanock, S, CLAVEL CHAPELON, F, Colditz, Ga, Cox, Dg, Feigelson, H, Hankinson, Se, Hayes, Rb, Henderson, Be, Hirschhorn, Jn, Hoover, R, Hunter, Dj, Kaaks, R, Kolonel, Ln, LE MARCHAND, L, Lenner, P, Lund, E, Panico, Salvatore, Peeters, Ph, Pike, Mc, Riboli, E, Tjonneland, A, Travis, R, Trichopoulos, D, Wacholder, S, and Ziegler, Rg
Subjects: Oncology, Cancer Research, Linkage disequilibrium, medicine.medical_specialty, Single-nucleotide polymorphism, Breast Neoplasms, Polymorphism, Single Nucleotide, Linkage Disequilibrium, Cohort Studies, Prostate cancer, Breast cancer, Aromatase, Gene Frequency, Risk Factors, Internal medicine, medicine, Humans, Allele frequency, Genetics, biology, Haplotype, Cancer, Estrogens, medicine.disease, Postmenopause, Haplotypes, Case-Control Studies, biology.protein, Female
Abstract: The CYP19A1 gene encodes the enzyme aromatase, which is responsible for the final step in the biosynthesis of estrogens. In this study, we used a systematic two-step approach that included gene resequencing and a haplotype-based analysis to comprehensively survey common genetic variation across the CYP19A1 locus in relation to circulating postmenopausal steroid hormone levels and breast cancer risk. This study was conducted among 5,356 invasive breast cancer cases and 7,129 controls comprised primarily of White women of European descent drawn from five large prospective cohorts within the National Cancer Institute Breast and Prostate Cancer Cohort Consortium. A high-density single-nucleotide polymorphism (SNP) map of 103 common SNPs (≥5% frequency) was used to identify the linkage disequilibrium and haplotype patterns across the CYP19A1 locus, and 19 haplotype-tagging SNPs were selected to provide high predictability of the common haplotype patterns. We found haplotype-tagging SNPs and common haplotypes spanning the coding and proximal 5′ region of CYP19A1 to be significantly associated with a 10% to 20% increase in endogenous estrogen levels in postmenopausal women [effect per copy of the two-SNP haplotype rs749292-rs727479 (A-A) versus noncarriers; P = 4.4 × 10−15]. No significant associations were observed, however, with these SNPs or common haplotypes and breast cancer risk. Thus, although genetic variation in CYP19A1 produces measurable differences in estrogen levels among postmenopausal women, the magnitude of the change was insufficient to contribute detectably to breast cancer. [Cancer Res 2007;67(5):1893–7]
Published: 2007

39. Endogenous androgens and risk of epithelial ovarian cancer: results from the European Prospective Investigation into Cancer and Nutrition (EPIC)

Author: Sheila Bingham, Domenico Palli, Françoise Clavel-Chapelon, Antonia Trichopoulou, Jenny Chang-Claude, Petra H.M. Peeters, Elio Riboli, Mandy Schulz, Göran Berglund, Kay-Tee Khaw, Valeria Pala, J. Ramón Quirós, Rudolf Kaaks, Kim Overvad, Merethe Kumle, Eleni Oikonomou, Sylvie Mesrine, Eva Ardanaz, Rosario Tumino, Anja Olsen, Rodolfo Saracci, Annekatrin Lukanova, María José Tormo, Nadia Slimani, Naomi E. Allen, Eiliv Lund, Åsa Ågren, Bas Bueno-de-Mesquita, Carmen Martinez-Garcia, Guillem Pera, Carla H. van Gils, Nerea Larrañaga, Paolo Vineis, Sabina Rinaldi, Jakob Linseisen, Heiner Boeing, Eva Lundin, Jonas Manjer, Timothy J. Key, Salvatore Panico, Marie-Christine Boutron-Ruault, Anne Tjønneland, Laure Dossus, Dimitrios Trichopoulos, Rinaldi, S, Dossus, L, Lukanova, A, Peeters, Ph, Allen, Ne, Key, T, Bingham, S, Khaw, Kt, Trichopoulos, D, Trichopoulou, A, Oikonomou, E, Pera, G, Larranaga, N, MARTINEZ GARCIA, C, Ardanaz, E, Quiros, Jr, Tormo, Mj, Tjonneland, A, Olsen, A, Overvad, K, CHANG CLAUDE, J, Linseisen, J, Schulz, M, Boeing, H, VAN GILS, Ch, BUENO DE MESQUITA, Bh, Pala, V, Palli, D, Panico, Salvatore, Tumino, R, Vineis, P, CLAVEL CHAPELON, F, Mesrine, S, BOUTRON RUAULT, Mc, Lundin, E, Agren, A, Berglund, G, Manjer, J, Kumle, M, Lund, E, Slimani, N, Saracci, R, Riboli, E, and Kaaks, R.
Subjects: Adult, medicine.medical_specialty, Epidemiology, medicine.drug_class, Physiology, Nutritional Status, Sex hormone-binding globulin, Risk Factors, Internal medicine, Sex Hormone-Binding Globulin, medicine, Humans, Testosterone, Prospective Studies, Risk factor, Prospective cohort study, Aged, Ovarian Neoplasms, biology, business.industry, Dehydroepiandrosterone Sulfate, Carcinoma, Case-control study, Odds ratio, Middle Aged, medicine.disease, Androgen, European Prospective Investigation into Cancer and Nutrition, Europe, Endocrinology, Oncology, Case-Control Studies, biology.protein, Female, Ovarian cancer, business
Abstract: Few epidemiologic studies have examined the hypothesis that circulating androgens are involved in the development of ovarian cancer. We investigated the association between prediagnostic serum levels of androgens and sex hormone–binding globulin (SHBG) and ovarian cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition cohort. One hundred and ninety-two ovarian cancer cases and 346 matched controls not using exogenous hormones at baseline blood donation were eligible for the study. Serum levels of testosterone, androstenedione, dehydroepiandrosterone sulfate, and SHBG were measured by direct immunoassays. Free testosterone (fT) was calculated according to mass action laws. Multivariate conditional logistic regression was used to estimate odds ratios adjusted for possible confounders. Overall, there was no association between serum concentrations of androgens or SHBG and ovarian cancer risk. In postmenopausal women, fT concentrations were inversely related to risk [highest versus lowest tertile odds ratio 0.45 (0.24-0.86); Ptrend = 0.01]. Among women diagnosed before the age of 55 years, there was a negative association with SHBG and a positive association with fT and ovarian cancer risk, although these associations were not statistically significant. The present study suggests that circulating androgens and SHBG levels are not strongly associated with ovarian cancer risk, although levels of fT may be associated with an increased risk among women diagnosed at relatively young age. The heterogeneity of results on the associations of fT with ovarian cancer risk in postmenopausal women deserves further investigation. (Cancer Epidemiol Biomarkers Prev 2007;16(1):23–9)
Published: 2007

40. Anthropometric measures, endogenous sex steroids and breast cancer risk in postmenopausal women: a study within the EPIC cohort

Author: Françoise Clavel-Chapelon, Elio Riboli, Domenico Palli, Paolo Vineis, Carmen Martinez, Sabina Rinaldi, J. Ramón Quirós, Diederick E. Grobbee, Rudolf Kaaks, Sheila Bingham, Pietro Ferrari, Antonia Trichopoulou, Nerea Larrañaga, Franco Berrino, Gabriele Nagel, Bertrand Tehard, Rosario Tumino, Timothy J. Key, Andrew W. Roddam, Petra H.M. Peeters, John Chloptios, Carlotta Sacerdote, Dimitrios Trichopoulos, Carine Biessy, Aurelio Barricarte, Nadia Slimani, Petra H. Lahmann, María Dolores Chirlaque, Salvatore Panico, Evelyne Monninkhof, Laure Dossus, Heiner Boeing, Annekatrin Lukanova, H. Bas Bueno-de-Mesquita, Carlos González, Jakob Linseisen, Kay-Tee Khaw, Rinaldi, S, Key, Tj, Peeters, Ph, Lahmann, Ph, Lukanova, A, Dossus, L, Biessy, C, Vineis, P, Sacerdote, C, Berrino, F, Panico, Salvatore, Tumino, R, Palli, D, Nagel, G, Linseisen, J, Boeing, H, Roddam, A, Bingham, S, Khaw, Kt, Chloptios, J, Trichopoulou, A, Trichopoulos, D, Tehard, B, CLAVEL CHAPELON, F, Gonzalez, Ca, Larranaga, N, Barricarte, A, Quiros, Jr, Chirlaque, Md, Martinez, C, Monninkhof, E, Grobbee, De, BUENO DE MESQUITA, Hb, Ferrari, P, Slimani, N, Riboli, E, and Kaaks, R.
Subjects: Cancer Research, medicine.medical_specialty, Waist, Breast Neoplasms, Estrone, Body Mass Index, chemistry.chemical_compound, Breast cancer, Sex hormone-binding globulin, Risk Factors, Sex Hormone-Binding Globulin, Internal medicine, medicine, Humans, Mass index, ddc:610, Risk factor, Gonadal Steroid Hormones, Adiposity, Aged, biology, business.industry, Middle Aged, medicine.disease, European Prospective Investigation into Cancer and Nutrition, Postmenopause, Endocrinology, Oncology, chemistry, Case-Control Studies, biology.protein, Female, business, Body mass index
Abstract: In a large case-control study on breast cancer risk and serum hormone concentrations, nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we examined to what extent the relationship of excess body weight with breast cancer risk may be explained by changes in sex steroids. Height, weight, waist and hip circumferences, and serum measurements of testosterone [T], androstenedione [Delta4], dehydroepiandrosterone sulphate [DHEAS], estradiol [E2], estrone [E1] and sex-hormone binding globulin [SHBG] were available for 613 breast cancer cases, and 1,139 matched controls, who were all menopausal at the time of blood donation. Free T [fT] and free E2 [fE2] were calculated using mass action equations. Breast cancer risk was related to body mass index (BMI) (RR = 1.11 [0.99-1.25], per 5 kg/m2 increase in BMI), and waist (RR = 1.12 [1.02-1.24], per 10 cm increase) and hip circumferences (RR = 1.14 [1.02-1.27], per 10 cm increase). The increase in breast cancer risk associated with adiposity was substantially reduced after adjustment for any estrogens, especially for fE2 (from 1.11 [0.99-1.25] to 0.99 [0.87-1.12], from 1.12 [1.02-1.24] to 1.02 [0.92-1.14] and from 1.14 [1.02-1.27] to 1.05 [0.93-1.18] for BMI, waist and hip circumferences, respectively). A modest attenuation in excess risk was observed after adjustment for fT, but the remaining androgens had little effect on the association of body adiposity with breast cancer. Our data indicate that the relationship of adiposity with breast cancer in postmenopausal women could be partially explained by the increases in endogenous estrogens, and by a decrease in levels of SHBG.
Published: 2007

41. Diet, serum insulin-like growth factor-I and IGF-binding protein-3 in European women

Author: Sheila Bingham, Ramón Quirós, Antonia Trichopoulou, Naomi E. Allen, Rosario Tumino, Domenico Palli, E. Ardanoz, Salvatore Panico, J. Linseisen, Elio Riboli, Carlotta Sacerdote, M. C. Boutron-Ruault, M. J. Tormo, Victoria Kalapothaki, Gabriele Nagel, Rudolf Kaaks, Henning Grønbæk, F. Clavel-Chapelon, S. Rinaldi, Teresa Norat, Sabina Sieri, Timothy J. Key, Anja Olsen, Antonio Agudo, Anne Tjønneland, Laure Dossus, C. H. van Gils, Nadia Slimani, Petra H. Lahmann, Dimitrios Trichopoulos, Pilar Amiano, Pamela Ferrari, Heiner Boeing, Kim Overvad, H. B. Bueno-De-Mesquita, Carlos Martinez, Petra H.M. Peeters, Norat, T, Dossus, L, Rinaldi, S, Overvad, K, Gronbaek, H, Tjonneland, A, Olsen, A, CLAVEL CHAPELON, F, BOUTRON RUAULT, Mc, Boeing, H, Lahmann, Ph, Linseisen, J, Nagel, G, Trichopoulou, A, Trichopoulos, D, Kalapothaki, V, Sieri, S, Palli, D, Panico, Salvatore, Tumino, R, Sacerdote, C, BUENO DE MESQUITA, Hb, Peeters, Ph, VAN GILS, Ch, Agudo, A, Amiano, P, Ardanoz, E, Martinez, C, Quiros, R, Tormo, Mj, Bingham, S, Key, Tj, Allen, Ne, Ferrari, P, Slimani, N, Riboli, E, and Kaaks, R.
Subjects: Adult, medicine.medical_specialty, medicine.medical_treatment, Population, Medicine (miscellaneous), Cohort Studies, Insulin-like growth factor, Surveys and Questionnaires, Internal medicine, Humans, Medicine, ddc:610, Prospective Studies, Insulin-Like Growth Factor I, Prospective cohort study, education, Aged, education.field_of_study, Nutrition and Dietetics, business.industry, Case-control study, Middle Aged, Diet, European Prospective Investigation into Cancer and Nutrition, Europe, Cross-Sectional Studies, Insulin-Like Growth Factor Binding Protein 3, Endocrinology, Case-Control Studies, Cohort, Female, Dairy Products, business, Body mass index, Cohort study
Abstract: OBJECTIVE: The aim of this study was to examine the relationship of diet with serum insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 in women. DESIGN: Cross-sectional study. SETTING AND SUBJECTS: The population are 2109 women who were control subjects in a case-control study of breast cancer nested in the European Prospective Investigation into Cancer and Nutrition. Control subjects were randomly chosen among risk sets consisting of female cohort members alive and free of cancer (except non-melanoma skin cancer) at the time of diagnosis of the index case. Matching criteria were age at enrolment, follow-up time, time of the day of blood collection and study centre. Diet was measured through validated questionnaires. Serum hormone concentrations were measured by enzyme-linked immunosorbent assays. The relationship between serum IGF-I, IGFBP-3, and intake of nutrients and foods was explored by linear regression in models adjusted for energy intake, age, body mass index, smoking, physical activity, centre and laboratory batch. RESULTS: Serum IGF-I levels were positively related to protein intake (P(trend)
Published: 2007

42. Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for Thirteen Cancer Types

Author: Yeul Hong Kim, Sonja I. Berndt, José María Huerta, Morgan Rouprêt, Reury Perng Perng, Yi Young Choi, Lindsay M. Morton, Roberto Tirabosco, H. Bas Bueno-de-Mesquita, Wendy Cozen, Neil E. Caporaso, Stephen J. Chanock, Zhenhong Zhao, Dina Halai, Neyssa Marina, Ann L. Oberg, Stephen M. Ansell, Zhibin Hu, Donghui Li, Anne J. Novak, Jenny Turner, Wen Tan, Julie E. Buring, Stefano Porru, Qincheng He, Tania Carreón, Guoping Wu, Graham G. Giles, Claire M. Vajdic, Rudolf Kaaks, Ulrika Andersson, Susan L. Slager, Jen Yu Hung, Luis Sierrasesúmaga, Roel Vermeulen, Louise A. Brinton, Myron D. Gross, Jennifer Prescott, E. Lund, Chih Yi Chen, Jin Eun Choi, Chaoyu Wang, George J. Weiner, H. Dean Hosgood, Haixin Li, Carrie A. Thompson, Núria Malats, James McKay, Stephanie J. Weinstein, Young Tae Kim, Emily White, Pan-Chyr Yang, Orestis A. Panagiotou, Robert J. Klein, Joseph Vijai, Josep Lloreta, Immaculata De Vivo, Sofia Pavanello, Thomas E. Witzig, Montserrat Garcia-Closas, Roger Henriksson, Bryan A. Bassig, Tait D. Shanafelt, Rachel S. Kelly, Joseph M. Connors, Marco Rais, Wu Chou Su, Alex Smith, John J. Spinelli, Julie M. Gastier-Foster, Anne Kricker, In Kyu Park, Marc J. Gunter, Chancellor Hohensee, Simon Crouch, Jarmo Virtamo, M. G. Ennas, Lucia Conde, Lotte Maxild Mortensen, Lenka Foretova, Eric J. Duell, Anthony Staines, Hongyan Chen, Baosen Zhou, Brian M. Wolpin, Simone Benhamou, Zhaoming Wang, Françoise Clavel-Chapelon, Charles C. Chung, Nan Hu, Domenico Palli, Rebecca Montalvan, Thomas M. Habermann, Debra T. Silverman, Preetha Rajaraman, Christian C. Abnet, Wei-Yen Lim, Yuh Min Chen, Michelle Cotterchio, Lucia Miligi, Claudia Maria Hattinger, Eve Roman, Christopher Kim, Federico Canzian, Alan D. L. Sihoe, Sharon A. Savage, Mark P. Purdue, Maria Teresa Landi, Susan M. Gapstur, M Zucca, Yuanqing Ye, Jian Su, Chong-Jen Yu, Edward Giovannucci, Alain Monnereau, Afshan Siddiq, Ralph L. Erickson, Katherine A. McGlynn, Petra H.M. Peeters, W. Ryan Diver, David Van Den Berg, Gloria M. Petersen, Judith Hoffman-Bolton, Xiao-Ou Shu, Ying Chen, Eric J. Jacobs, Heiner Boeing, Sophia S. Wang, Hans-Olov Adami, Yuqing Li, Jacqueline Clavel, Ellen T. Chang, Tongzhang Zheng, William Pao, Hideo Kunitoh, Ulrike Peters, Jenny Chang-Claude, Alexandra Nieters, Silvia de Sanjosé, Chen Wu, Anders Ahlbom, Jun Suk Kim, Fredrick R. Schumacher, Roberta McKean-Cowdin, Laurence N. Kolonel, Herbert Yu, Li Liu, Vittorio Krogh, Tangchun Wu, Ho Il Yoon, Joseph F. Fraumeni, Olivier Cussenot, Jae Sook Sung, Kari E. North, Andrew D. Zelenetz, Ana Patiño-García, Anne Zeleniuch-Jacquotte, Christopher A. Haiman, Biyun Qian, Giovanni Maria Ferri, Rebecca Rodabough, Xifeng Wu, Maria Feychting, Kuan-Yu Chen, Laure Dossus, Jianjun Liu, Jean Wactawski-Wende, Constance Chen, Robert L. Grubb, Paolo Vineis, Mads Melbye, Chien Chung Lin, Malin Sund, Wei Zheng, Jun Xu, Yi Song Chen, Kay-Tee Khaw, Richard K. Severson, Kun-Chieh Chen, Jian-Min Yuan, Bu Tian Ji, Simonetta Di Lollo, Ping Xu, Howard D. Sesso, Yoo Jin Jung, Margaret R. Karagas, Piero Picci, Gianluca Severi, Margaret A. Tucker, Ti Ding, Gee-Chen Chang, Li Hsin Chien, She-Juan An, Maria Pik Wong, Chien-Jen Chen, Jonine D. Figueroa, Sun-Seog Kweon, Katia Scotlandi, Sara H. Olson, Kendra Schwartz, Chang Hyun Kang, Marta Crous-Bou, Yawei Zhang, Ludmila Prokunina-Olsson, Yolanda Benavente, Christine D. Berg, Kala Visvanathan, Loic Le Marchand, Takashi Kohno, Nilanjan Chatterjee, Tracy Lightfoot, Zhihua Yin, Lee E. Moore, Joanne S. Colt, Laurie Burdett, Tetsuya Mitsudomi, Harvey A. Risch, Alfredo Carrato, Hyo Sung Jeon, Victoria L. Stevens, Richard Gorlick, Danylo J. Villano, Alison P. Klein, Angela Brooks-Wilson, Joshua N. Sampson, Chu Chen, You-Lin Qiao, Kouya Shiraishi, Alan R. Schned, Dominique S. Michaud, Peng Guan, Philip R. Taylor, Gerald L. Andriole, John K.C. Chan, Eva Comperat, Randy D. Gascoyne, Marc Maynadie, Kyong Hwa Park, Amanda Black, Charles Kooperberg, Andrea La Croix, Kenneth Offit, Peter Kraft, David Thomas, Manuela Gago-Dominguez, Manolis Kogevinas, Theodore R. Holford, Pamela L. Horn-Ross, Xingzhou He, Massimo Serra, Satu Männistö, Christoffer Johansen, Meredith Yeager, Robert N. Hoover, Mary Ann Butler, William Wheeler, Jian Gu, Wei Wu, Ying Hsiang Chen, Leslie Bernstein, Yao Jen Li, David J. Hunter, In-Jae Oh, Jay S. Wunder, Meng Zhu, Henrik Hjalgrim, Martyn T. Smith, Alisa M. Goldstein, Linda M. Liao, Chao Agnes Hsiung, Ruth C. Travis, Jiucun Wang, Marie-Christine Boutron-Ruault, Daru Lu, Reina García-Closas, Avima M. Ruder, Martha S. Linet, Wei Tang, Geraldine Cancel-Tassin, Brian K. Link, Rebecca D. Jackson, J. Michael Gaziano, Malcolm C. Pike, Yu-Tang Gao, Lisa Mirabello, Alan A. Arslan, Hong Zheng, Nicolas Wentzensen, Chung Hsing Chen, I. Shou Chang, Meir J. Stampfer, Brenda M. Birmann, Alison Johnson, Wong-Ho Chow, Chin-Fu Hsiao, Neal D. Freedman, Robert C. Kurtz, Donald A. Barkauskas, Steven Gallinger, Junwen Wang, Simina M. Boca, Irene L. Andrulis, Hongbing Shen, Adrienne M. Flanagan, Cosmeri Rizzato, Marianna C. Stern, Angela Carta, Melissa C. Southey, Corrado Magnani, Sook Whan Sung, Lesley F. Tinker, M. Dorronsoro, Guangfu Jin, Giovanna Masala, Yi-Long Wu, Min-Ho Shin, Ming Shyan Huang, Göran Hallmans, Xueying Zhao, Jacques Riby, Beatrice Melin, Adonina Tardón, Börje Ljungberg, Mark Liebow, Elizabeth A. Holly, Carol Giffen, Paolo Boffetta, Maria Fernanda Amary, Jihua Li, Mazda Jenab, Keitaro Matsuo, Nalan Gokgoz, Karin E. Smedby, Cari M. Kitahara, Mia M. Gaudet, Cecilia Arici, Brian E. Henderson, Amy Hutchinson, Elio Riboli, Patricia Hartge, Victoria K. Cortessis, Kexin Chen, Dalsu Baris, Michael Goggins, Young-Chul Kim, Tsung-Ying Yang, Fusheng Wei, Peter D. Inskip, Demetrius Albanes, Fang Yu Tsai, Qing Lan, Li Jin, Charles E. Lawrence, Nikolaus Becker, Rachael S. Stolzenberg-Solomon, Bengt Glimelius, Wei Hu, Maria Dolores Chirlaque, Kimberly A. Bertrand, Bruce K. Armstrong, Veronica Wendy Setiawan, Kathy J. Helzlsouer, Manal M. Hassan, Jun Yokota, David V. Conti, Kai Yu, Chenwei Liu, Christine F. Skibola, Jae Yong Park, Fernando Lecanda, Dimitrios Trichopoulos, Eleanor Kane, Dongxin Lin, Yun-Chul Hong, Consol Serra, Anne Tjønneland, Melissa A. Austin, X. Zhang, Charles S. Fuchs, Nathaniel Rothman, Paul Brennan, Chih-Liang Wang, Wei Shen, Ying-Huang Tsai, Hee Nam Kim, Ghislaine Scelo, Faith G. Davis, Sara Lindström, Molly Schwenn, Giuseppe Mastrangelo, Adeline Seow, Laufey T. Amundadottir, Laura E. Beane Freeman, Huan Guo, Victor Ho-Fun Lee, Aruna Kamineni, Pierluigi Cocco, Jiang Chang, Emanuele Angelucci, Paige M. Bracci, Yong-Bing Xiang, G. M. Monawar Hosain, Elisabete Weiderpass, James R. Cerhan, Junjie Wu, Lauren R. Teras, Jin Hee Kim, Qiuyin Cai, Sampson, J.N., Wheeler, W.A., Yeager, M., Panagiotou, O., Wang, Z., Berndt, S.I., Lan, Q., Abnet, C.C., Amundadottir, L.T., Figueroa, J.D., Landi, M.T., Mirabello, L., Savage, S.A., Taylor, P.R., De Vivo, I., McGlynn, K.A., Purdue, M.P., Rajaraman, P., Adami, H.-O., Ahlbom, A., Albanes, D., Amary, M.F., An, S.-J., Andersson, U., Andriole, G., Jr., Andrulis, I.L., Angelucci, E., Ansell, S.M., Arici, C., Armstrong, B.K., Arslan, A.A., Austin, M.A., Baris, D., Barkauskas, D.A., Bassig, B.A., Becker, N., Benavente, Y., Benhamou, S., Berg, C., Van Den Berg, D., Bernstein, L., Bertrand, K.A., Birmann, B.M., Black, A., Boeing, H., Boffetta, P., Boutron-Ruault, M.-C., Bracci, P.M., Brinton, L., Brooks-Wilson, A.R., Bueno-De-Mesquita, H.B., Burdett, L., Buring, J., Butler, M.A., Cai, Q., Cancel-Tassin, G., Canzian, F., Carrato, A., Carreon, T., Carta, A., Chan, J.K.C., Chang, E.T., Chang, G.-C., Chang, I.S., Chang, J., Chang-Claude, J., Chen, C.-J., Chen, C.-Y., Chen, C., Chen, C.-H., Chen, H., Chen, K., Chen, K.-Y., Chen, K.-C., Chen, Y., Chen, Y.-H., Chen, Y.-S., Chen, Y.-M., Chien, L.-H., Chirlaque, M.-D., Choi, J.E., Choi, Y.Y., Chow, W.-H., Chung, C.C., Clavel, J., Clavel-Chapelon, F., Cocco, P., Colt, J.S., Comperat, E., Conde, L., Connors, J.M., Conti, D., Cortessis, V.K., Cotterchio, M., Cozen, W., Crouch, S., Crous-Bou, M., Cussenot, O., Davis, F.G., Ding, T., Diver, W.R., Dorronsoro, M., Dossus, L., Duell, E.J., Ennas, M.G., Erickson, R.L., Feychting, M., Flanagan, A.M., Foretova, L., Fraumeni, J.F., Jr., Freedman, N.D., Freeman, L.E.B., Fuchs, C., Gago-Dominguez, M., Gallinger, S., Gao, Y.-T., Gapstur, S.M., Garcia-Closas, M., García-Closas, R., Gascoyne, R.D., Gastier-Foster, J., Gaudet, M.M., Gaziano, J.M., Giffen, C., Giles, G.G., Giovannucci, E., Glimelius, B., Goggins, M., Gokgoz, N., Goldstein, A.M., Gorlick, R., Gross, M., Grubb, R., III and Gu, J., Guan, P., Gunter, M., Guo, H., Habermann, T.M., Haiman, C.A., Halai, D., Hallmans, G., Hassan, M., Hattinger, C., He, Q., He, X., Helzlsouer, K., Henderson, B., Henriksson, R., Hjalgrim, H., Hoffman-Bolton, J., Hohensee, C., Holford, T.R., Holly, E.A., Hong, Y.-C., Hoover, R.N., Horn-Ross, P.L., Hosain, G.M.M., Hosgood, H.D., III and Hsiao, C.-F., Hu, N., Hu, W., Hu, Z., Huang, M.-S., Huerta, J.-M., Hung, J.-Y., Hutchinson, A., Inskip, P.D., Jackson, R.D., Jacobs, E.J., Jenab, M., Jeon, H.-S., Ji, B.-T., Jin, G., Jin, L., Johansen, C., Johnson, A., Jung, Y.J., Kaaks, R., Kamineni, A., Kane, E., Kang, C.H., Karagas, M.R., Kelly, R.S., Khaw, K.-T., Kim, C., Kim, H.N., Kim, J.H., Kim, J.S., Kim, Y.H., Kim, Y.T., Kim, Y.-C., Kitahara, C.M., Klein, A.P., Klein, R.J., Kogevinas, M., Kohno, T., Kolonel, L.N., Kooperberg, C., Kricker, A., Krogh, V., Kunitoh, H., Kurtz, R.C., Kweon, S.-S., La Croix, A., Lawrence, C., Lecanda, F., Lee, V.H.F., Li, D., Li, H., Li, J., Li, Y.-J., Li, Y., Liao, L.M., Liebow, M., Lightfoot, T., Lim, W.-Y., Lin, C.-C., Lin, D., Lindstrom, S., Linet, M.S., Link, B.K., Liu, C., Liu, J., Liu, L., Ljungberg, B., Lloreta, J., Di Lollo, S., Lu, D., Lund, E., Malats, N., Mannisto, S., Marchand, L.L., Marina, N., Masala, G., Mastrangelo, G., Matsuo, K., Maynadie, M., McKay, J., McKean-Cowdin, R., Melbye, M., Melin, B.S., Michaud, D.S., Mitsudomi, T., Monnereau, A., Montalvan, R., Moore, L.E., Mortensen, L.M., Nieters, A., North, K.E., Novak, A.J., Oberg, A.L., Offit, K., Oh, I.-J., Olson, S.H., Palli, D., Pao, W., Park, I.K., Park, J.Y., Park, K.H., Patiño-Garcia, A., Pavanello, S., Peeters, P.H.M., Perng, R.-P., Peters, U., Petersen, G.M., Picci, P., Pike, M.C., Porru, S., Prescott, J., Prokunina-Olsson, L., Qian, B., Qiao, Y.-L., Rais, M., Riboli, E., Riby, J., Risch, H.A., Rizzato, C., Rodabough, R., Roman, E., Roupret, M., Ruder, A.M., De Sanjose, S., Scelo, G., Schned, A., Schumacher, F., Schwartz, K., Schwenn, M., Scotlandi, K., Seow, A., Serra, C., Serra, M., Sesso, H.D., Setiawan, V.W., Severi, G., Severson, R.K., Shanafelt, T.D., Shen, H., Shen, W., Shin, M.-H., Shiraishi, K., Shu, X.-O., Siddiq, A., Sierrasesúmaga, L., Sihoe, A.D.L., Skibola, C.F., Smith, A., Smith, M.T., Southey, M.C., Spinelli, J.J., Staines, A., Stampfer, M., Stern, M.C., Stevens, V.L., Stolzenberg-Solomon, R.S., Su, J., Su, W.-C., Sund, M., Sung, J.S., Sung, S.W., Tan, W., Tang, W., Tardón, A., Thomas, D., Thompson, C.A., Tinker, L.F., Tirabosco, R., Tjønneland, A., Travis, R.C., Trichopoulos, D., Tsai, F.-Y., Tsai, Y.-H., Tucker, M., Turner, J., Vajdic, C.M., Vermeulen, R.C.H., Villano, D.J., Vineis, P., Virtamo, J., Visvanathan, K., Wactawski-Wende, J., Wang, C., Wang, C.-L., Wang, J.-C., Wang, J., Wei, F., Weiderpass, E., Weiner, G.J., Weinstein, S., Wentzensen, N., White, E., Witzig, T.E., Wolpin, B.M., Wong, M.P., Wu, C., Wu, G., Wu, J., Wu, T., Wu, W., Wu, X., Wu, Y.-L., Wunder, J.S., Xiang, Y.-B., Xu, J., Xu, P., Yang, P.-C., Yang, T.-Y., Ye, Y., Yin, Z., Yokota, J., Yoon, H.-I., Yu, C.-J., Yu, H., Yu, K., Yuan, J.-M., Zelenetz, A., Zeleniuch-Jacquotte, A., Zhang, X.-C., Zhang, Y., Zhao, X., Zhao, Z., Zheng, H., Zheng, T., Zheng, W., Zhou, B., Zhu, M., Zucca, M., Boca, S.M., Cerhan, J.R., Ferri, G.M., Hartge, P., Hsiung, C.A., Magnani, C., Miligi, L., Morton, L.M., Smedby, K.E., Teras, L.R., Vijai, J., Wang, S.S., Brennan, P., Caporaso, N.E., Hunter, D.J., Kraft, P., Rothman, N., Silverman, D.T., Slager, S.L., Chanock, S.J., Chatterjee, N., Infection & Immunity, dIRAS RA-I&I RA, LS IRAS EEPI GRA (Gezh.risico-analyse), and Risk Assessment
Subjects: Male, Cancer Research, Lung Neoplasms, Lymphoma, Genome-wide association study, Polymorphism (computer science), Neoplasms, Medicine, Chronic, Genetics, Osteosarcoma, Oncology And Carcinogenesis, Leukemia, Smoking, Family aggregation, Single Nucleotide, Middle Aged, Familial risk, Diffuse, Kidney Neoplasms, Lymphocytic, Oncology, Adult, Aged, Asian Continental Ancestry Group, Bone Neoplasms, European Continental Ancestry Group, Female, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Large B-Cell, Diffuse, Polymorphism, Single Nucleotide, Testicular Neoplasms, Tissue Array Analysis, Urinary Bladder Neoplasms, Genetic Predisposition to Disease, Genome-Wide Association Study, Genetic correlation, Large B-Cell, Oncology & Carcinogenesis, Polymorphism, business.industry, Extramural, B-Cell, Cancer, Heritability, Genome-wide association studies for thirteen cancer types, medicine.disease, business
Abstract: BACKGROUND: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites.METHODS: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers.RESULTS: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, hl (2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (ρ = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (ρ = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (ρ = 0.51, SE =0.18), and bladder and lung (ρ = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures.CONCLUSION: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
Published: 2015

43. Relationship of alcohol intake and sex steroid concentrations in blood in pre- and post-menopausal women: the European Prospective Investigation into Cancer and Nutrition

Author: Antonio Agudo, Elio Riboli, Kay-Tee Khaw, Gabriele Nagel, R. Saracci, H. B. Bueno-De-Mesquita, S. Rinaldi, Carmen Martinez-Garcia, Petra H.M. Peeters, Salvatore Panico, Kim Overvad, Naomi E. Allen, Anne Tjønneland, Sheila Bingham, Michael Schulz, A. Olsen, Laure Dossus, Françoise Clavel-Chapelon, Majken K. Jensen, Franco Berrino, Carine Biessy, Irene D. Bezemer, Domenico Palli, Diederik E. Grobbee, J. Linseisen, Timothy J. Key, Rosario Tumino, J. Ramón Quirós, A. Thrichopoulou, Eva Ardanaz, Pilar Amiano, Maria Koliva, Carlotta Sacerdote, M. J. Tormo, G. Kyriazi, M. C. Boutron-Ruault, Rudolf Kaaks, Heiner Boeing, Nadia Slimani, Pamela Ferrari, Rinaldi, S, Peeters, Ph, Bezemer, Id, Dossus, L, Biessy, C, Sacerdote, C, Berrino, F, Panico, Salvatore, Palli, D, Tumino, R, Khaw, Kt, Bingham, S, Allen, Ne, Key, T, Jensen, Mk, Overvad, K, Olsen, A, Tjonneland, A, Amiano, P, Ardanaz, E, Agudo, A, MARTINEZ GARCIA, C, Quiros, Jr, Tormo, Mj, Nagel, G, Linseisen, J, Boeing, H, Schulz, M, Grobbee, De, BUENO DE MESQUITA, Hb, Koliva, M, Kyriazi, G, Thrichopoulou, A, BOUTRON RUAULT, Mc, CLAVEL CHAPELON, F, Ferrari, P, Slimani, N, Saracci, R, Riboli, E, and Kaaks, R.
Subjects: Adult, Male, Cancer Research, medicine.medical_specialty, Alcohol Drinking, Physiology, Alcohol, Models, Biological, chemistry.chemical_compound, Sex hormone-binding globulin, Breast cancer, Internal medicine, Neoplasms, Sex Hormone-Binding Globulin, Epidemiology, Medicine, Humans, Nutritional Physiological Phenomena, ddc:610, Gonadal Steroid Hormones, Aged, Hematology, biology, business.industry, Public health, Middle Aged, medicine.disease, European Prospective Investigation into Cancer and Nutrition, Postmenopause, Endocrinology, Oncology, chemistry, Premenopause, Sex steroid, biology.protein, Female, business
Abstract: Objective: Women with a moderate intake of alcohol have higher concentrations of sex steroids in serum, and higher risk of developing breast cancer, compared to non-drinkers. In the present study, we investigate the relationships between alcohol consumption and serum levels of sex steroids and sex-hormone binding globulin (SHBG) in 790 pre- and 1,291 post-menopausal women, who were part of the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods: Serum levels of testosterone (T), androstenedione (Δ4), dehydroepiandrosterone sulphate (DHEAS), estrone (E 1), estradiol (E2) and SHBG were measured by direct immunoassays. Free T (fT) and free E2 (fE2) were calculated according to mass action laws. Current alcohol intake exposure to alcohol was assessed from dietary questionnaires. Results: Pre-menopausal women who consumed more than 25 g/day of alcohol had about 30% higher DHEAS, T and fT, 20% higher Δ4 and about 40% higher E1, concentrations compared to women who were non-consumers. E2, fE 2 and SHBG concentrations showed no association with current alcohol intake. In post-menopausal women, DHEAS, fT, T, Δ4, and E 1 concentrations were between 10% and 20% higher in women who consumed more than 25 g/day of alcohol compared to non-consumers. E2 or fE2 were not associated with alcohol intake at all. SHBG levels were about 15% lower in alcohol consumers compared to non-consumers. Conclusion: This study supports the hypothesis of an influence of alcohol intake on sex hormone concentrations in blood. © Springer Science+Business Media B.V. 2006.
Published: 2006

44. Serum C-peptide levels and breast cancer risk: Results from the European prospective investigation into cancer and nutrition (EPIC)

Author: Kim Overvad, Elio Riboli, Sabina Sieri, Françoise Clavel-Chapelon, Martijn Verheus, Petra H.M. Peeters, Carlos González, Rosario Tumino, Kay-Tee Khaw, Carmen Navarro, Anja Olsen, Jakob Linseisen, Anne Tjønneland, Bertrand Tehard, J. Ramón Quirós, Laure Dossus, Nera Larranaga, Eva Ardanaz, Bas Bueno-de-Mesquita, Timothy J. Key, Carla H. van Gils, Domenico Palli, Rudolf Kaaks, Petra H. Lahmann, Nadia Slimani, Carlotta Sacerdote, Heiner Boeing, Theodora Psaltopoulou, Sabina Rinaldi, Sheila Bingham, Antonia Trichopoulou, Naomi E. Allen, Carine Biessy, Carmen Martinez Garcia, Majbritt Jeppesen, Gabriele Nagel, Athina Arvaniti, Salvatore Panico, Verheus, M, Peeters, Ph, Rinaldi, S, Dossus, L, Biessy, C, Olsen, A, Tjonneland, A, Overvad, K, Jeppesen, M, CLAVEL CHAPELON, F, Tehard, B, Nagel, G, Linseisen, J, Boeing, H, Lahmann, Ph, Arvaniti, A, Psaltopoulou, T, Trichopoulou, A, Palli, D, Tumino, R, Panico, Salvatore, Sacerdote, C, Sieri, S, VAN GILS, Ch, BUENO DE MESQUITA, Bh, Gonzalez, Ca, Ardanaz, E, Larranaga, N, Garcia, Cm, Navarro, C, Quiros, Jr, Key, T, Allen, N, Bingham, S, Khaw, Kt, Slimani, N, Riboli, E, and Kaaks, R.
Subjects: Adult, Cancer Research, medicine.medical_specialty, Physiology, Breast Neoplasms, Body Mass Index, Breast cancer, Sex hormone-binding globulin, Risk Factors, Internal medicine, Odds Ratio, medicine, Hyperinsulinemia, Humans, ddc:610, Risk factor, Testosterone, Aged, C-Peptide, biology, business.industry, Incidence, Case-control study, Odds ratio, Middle Aged, medicine.disease, European Prospective Investigation into Cancer and Nutrition, Europe, Postmenopause, Logistic Models, Endocrinology, Premenopause, Oncology, Case-Control Studies, Multivariate Analysis, biology.protein, Female, business
Abstract: It has been hypothesized that chronic hyperinsulinemia, a major metabolic consequence of physical inactivity and excess weight, might increase breast cancer risk by direct effects on breast tissue or indirectly by increasing bioavailable levels of testosterone and estradiol. Within the European Prospective Investigation into Cancer and Nutrition (EPIC), we measured serum levels of C-peptide--a marker for pancreatic insulin secretion--in a total of 1,141 incident cases of breast cancer and 2,204 matched control subjects. Additional measurements were made of serum sex hormone binding globulin (SHBG) and sex steroids. Conditional logistic regression models were used to estimate breast cancer risk for different levels of C-peptide. C-peptide was inversely correlated with SHBG and hence directly correlated with free testosterone among both pre and postmenopausal women. C-peptide and free estradiol also correlated positively, but only among postmenopausal women. Elevated serum C-peptide levels were associated with a nonsignificant reduced risk of breast cancer diagnosed up to the age of 50 years [odds ratio (OR)=0.70, (95% confidence interval (CI), 0.39-1.24); ptrend=0.05]. By contrast, higher levels of C-peptide were associated with an increase of breast cancer risk among women above 60 years of age, however only among those women who had provided a blood sample under nonfasting conditions [OR=2.03, (95% CI, 1.20-3.43); ptrend=0.01]. Our results do not support the hypothesis that chronic hyperinsulinemia generally increases breast cancer risk, independently of age. Nevertheless, among older, postmenopausal women, hyperinsulinemia might contribute to increasing breast cancer risk.
Published: 2006

45. Serum sex steroids in premenopausal women and breast cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC)

Author: Domenico Palli, Jenny Chang-Claude, Rudolf Kaaks, Carla H. van Gils, H. Bas Bueno de Mesquita, Petra H.M. Peeters, Pilar Amiano, Gabriele Nagel, Giorgio Secreto, Rosario Tumino, Dimitrios Trichopoulos, Agnès Fournier, Elio Riboli, Kay-Tee Khaw, Anne Tjønneland, Françoise Clavel-Chapelon, Nadia Slimani, Paolo Vineis, Laure Dossus, Sabina Rinaldi, N. Charlotte Onland-Moret, J. Ramón Quirós, Vittorio Krogh, Petra H. Lahmann, Anne C. M. Thiébaut, Teresa Norat, Carine Biessy, Sheila Bingham, Ma Dolores Chirlaque, Antonia Trichopoulou, Heiner Boeing, Kim Overvad, Anja Olsen, Franco Berrino, Elena Critselis, Salvatore Panico, Carlos A. González, Pietro Ferrari, Timothy J. Key, Aurelio Barricarte Gurrea, Andrew W. Roddam, Kaaks, R, Berrino, F, Key, T, Rinaldi, S, Dossus, L, Biessy, C, Secreto, G, Amiano, P, Bingham, S, Boeing, H, BUENO DE MESQUITA, Hb, CHANG CLAUDE, J, CLAVEL CHAPELON, F, Fournier, A, VAN GILS, Ch, Gonzalez, Ca, Gurrea, Ab, Critselis, E, Khaw, Kt, Krogh, V, Lahmann, Ph, Nagel, G, Olsen, A, ONLAND MORET, Nc, Overvad, K, Palli, D, Panico, Salvatore, Peeters, P, Quiros, Jr, Roddam, A, Thiebaut, A, Tjonneland, A, Chirlaque, Md, Trichopoulou, A, Trichopoulos, D, Tumino, R, Vineis, P, Norat, T, Ferrari, P, Slimani, N, and Riboli, E.
Subjects: Oncology, Adult, Cancer Research, medicine.medical_specialty, medicine.drug_class, Urology, Breast Neoplasms, EPIC, Risk Assessment, Breast cancer, Sex hormone-binding globulin, Risk Factors, Sex Hormone-Binding Globulin, Internal medicine, Confidence Intervals, Odds Ratio, medicine, Humans, Testosterone, Prospective Studies, Risk factor, Gonadal Steroid Hormones, Prospective cohort study, Menstrual Cycle, biology, Dehydroepiandrosterone Sulfate, business.industry, Cancer, Confounding Factors, Epidemiologic, Dehydroepiandrosterone, Middle Aged, medicine.disease, European Prospective Investigation into Cancer and Nutrition, Europe, Logistic Models, Endocrinology, Premenopause, Quartile, Estrogen, Case-Control Studies, biology.protein, Female, business
Abstract: Contrasting etiologic hypotheses about the role of endogenous sex steroids in breast cancer development among premenopausal women implicate ovarian androgen excess and progesterone deficiency, estrogen excess, estrogen and progesterone excess, and both an excess or lack of adrenal androgens (dehydroepiandrosterone [DHEA] or its sulfate [DHEAS]) as risk factors. We conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition cohort to examine associations among premenopausal serum concentrations of sex steroids and subsequent breast cancer risk.Levels of DHEAS, (Delta4-)androstenedione, testosterone, and sex hormone binding globulin (SHBG) were measured in single prediagnostic serum samples from 370 premenopausal women who subsequently developed breast cancer (case patients) and from 726 matched cancer-free control subjects. Levels of progesterone, estrone, and estradiol were also measured for the 285 case patients and 555 matched control subjects who had provided information about the day of menstrual cycle at blood donation. Conditional logistic regression models were used to estimate relative risks of breast cancer by quartiles of hormone concentrations. All statistical tests were two-sided.Increased risks of breast cancer were associated with elevated serum concentrations of testosterone (odds ratio [OR] for highest versus lowest quartile = 1.73, 95% confidence interval [CI] = 1.16 to 2.57; P(trend) = .01), androstenedione (OR for highest versus lowest quartile = 1.56, 95% CI = 1.05 to 2.32; P(trend) = .01), and DHEAS (OR for highest versus lowest quartile = 1.48, 95% CI = 1.02 to 2.14; P(trend) = .10) but not SHBG. Elevated serum progesterone concentrations were associated with a statistically significant reduction in breast cancer risk (OR for highest versus lowest quartile = 0.61, 95% CI = 0.38 to 0.98; P(trend) = .06). The absolute risk of breast cancer for women younger than 40 followed up for 10 years was estimated at 2.6% for those in the highest quartile of serum testosterone versus 1.5% for those in the lowest quartile; for the highest and lowest quartiles of progesterone, these estimates were 1.7% and 2.6%, respectively. Breast cancer risk was not statistically significantly associated with serum levels of the other hormones.Our results support the hypothesis that elevated blood concentrations of androgens are associated with an increased risk of breast cancer in premenopausal women.
Published: 2005

46. Postmenopausal serum androgens, oestrogens and breast cancer risk: the European prospective investigation into cancer and nutrition

Author: Domenico Palli, Naomi E. Allen, Rudolph Kaaks, H. B. Bueno-De-Mesquita, Jenny Chang-Claude, Carine Biessy, Laure Dossus, Pilar Amiano, Paolo Vineis, Petra H.M. Peeters, R. Tumino, C. H. van Gils, Gabriele Nagel, Annekatrin Lukanova, Agnès Fournier, R. Saracci, S. Rinaldi, F. Clavel-Chapelon, Salvatore Panico, Teresa Norat, Pietro Ferrari, Elio Riboli, Victoria Kalapothaki, J. R. Quirós, M. J. Tormo, Timothy J. Key, Petra H. Lahmann, Dimitrios Trichopoulos, K-T Khaw, H. Boeing, Franco Berrino, Diederik E. Grobbee, Carlos A. González, Anne C. M. Thiébaut, E. Ardanaz, Vittorio Krogh, Sheila Bingham, Antonia Trichopoulou, University of Groningen, Kaaks, R, Rinaldi, S, Key, Tj, Berrino, F, Peeters, Ph, Biessy, C, Dossus, L, Lukanova, A, Bingham, S, Khaw, Kt, Allen, Ne, BUENO DE MESQUITA, Hb, VAN GILS, Ch, Grobbee, D, Boeing, H, Lahmann, Ph, Nagel, G, CHANG CLAUDE, J, CLAVEL CHAPELON, F, Fournier, A, Thiebaut, A, Gonzalez, Ca, Quiros, Jr, Tormo, Mj, Ardanaz, E, Amiano, P, Krogh, V, Palli, D, Panico, Salvatore, Tumino, R, Vineis, P, Trichopoulou, A, Kalapothaki, V, Trichopoulos, D, Ferrari, P, Norat, T, Saracci, R, and Riboli, E.
Subjects: Male, PREMENOPAUSAL, Cancer Research, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Cohort Studies, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Sex hormone-binding globulin, Risk Factors, TESTOSTERONE, Medicine, Nutritional Physiological Phenomena, skin and connective tissue diseases, ESTRADIOL, Testosterone, 2. Zero hunger, 0303 health sciences, biology, WOMEN, Middle Aged, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Postmenopause, Oncology, 030220 oncology & carcinogenesis, RELIABILITY, Androgens, Female, COLLABORATIVE REANALYSIS, Androgen replacement therapy, hormones, hormone substitutes, and hormone antagonists, medicine.medical_specialty, DEHYDROEPIANDROSTERONE-SULFATE, Dehydroepiandrosterone, Breast Neoplasms, URINARY ANDROGENS, Geneeskunde, REPLACEMENT THERAPY, 03 medical and health sciences, Breast cancer, Dehydroepiandrosterone sulfate, Internal medicine, Humans, Risk factor, SEX-HORMONE LEVELS, Aged, 030304 developmental biology, business.industry, Estrogens, medicine.disease, chemistry, Case-Control Studies, biology.protein, business
Abstract: Considerable experimental and epidemiological evidence suggests that elevated endogenous sex steroids — notably androgens and oestrogens — promote breast tumour development. In spite of this evidence, postmenopausal androgen replacement therapy with dehydroepiandrosterone (DHEA) or testosterone has been advocated for the prevention of osteoporosis and improved sexual well-being. We have conducted a case–control study nested within the European Prospective Investigation into Cancer and Nutrition. Levels of DHEA sulphate (DHEAS), (Δ4-androstenedione), testosterone, oestrone, oestradiol and sex-hormone binding globulin (SHBG) were measured in prediagnostic serum samples of 677 postmenopausal women who subsequently developed breast cancer and 1309 matched control subjects. Levels of free testosterone and free oestradiol were calculated from absolute concentrations of testosterone, oestradiol and SHBG. Logistic regression models were used to estimate relative risks of breast cancer by quintiles of hormone concentrations. For all sex steroids –the androgens as well as the oestrogens – elevated serum levels were positively associated with breast cancer risk, while SHBG levels were inversely related to risk. For the androgens, relative risk estimates (95% confidence intervals) between the top and bottom quintiles of the exposure distribution were: DHEAS 1.69 (1.23–2.33), androstenedione 1.94 (1.40–2.69), testosterone 1.85 (1.33–2.57) and free testosterone 2.50 (1.76–3.55). For the oestrogens, relative risk estimates were: oestrone 2.07 (1.42–3.02), oestradiol 2.28 (1.61–3.23) and free oestradiol (odds ratios 2.13 (1.52–2.98)). Adjustments for body mass index or other potential confounding factors did not substantially alter any of these relative risk estimates. Our results have shown that, among postmenopausal women, not only elevated serum oestrogens but also serum androgens are associated with increased breast cancer risk. Since DHEAS and androstenedione are largely of adrenal origin in postmenopausal women, our results indicated that elevated adrenal androgen synthesis is a risk factor for breast cancer. The results from this study caution against the use of DHEA(S), or other androgens, for postmenopausal androgen replacement therapy.
Published: 2005

47. IGF-I, IGFBP-3 and breast cancer risk in women: The European Prospective Investigation into Cancer and Nutrition (EPIC)

Author: M. C. Boutron-Ruault, Rudolf Kaaks, P.A.H. van Noord, Antonio Agudo, Naomi E. Allen, Franco Berrino, Annekatrin Lukanova, Kim Overvad, Gabriele Nagel, Salvatore Panico, Kay-Tee Khaw, Sheila Bingham, Heiner Boeing, Carlotta Sacerdote, Timothy J. Key, Françoise Clavel-Chapelon, Aurelio Barricarte, Antonia Trichopoulou, H. B. Bueno-De-Mesquita, M-D Chirlaque, Carine Biessy, Bertrand Tehard, C. H. van Gils, Domenico Palli, Nadia Slimani, J. Linseisen, Elio Riboli, Dimitrios Trichopoulos, C. A. Gonzalez, Anne Tjønneland, A. Olsen, P. H. M. Peeters, Maria Koliva, Laure Dossus, Rosario Tumino, J. R. Quirós, Petra H. Lahmann, R. Saracci, S. Rinaldi, Nerea Larrañaga, Diederik E. Grobbee, Rinaldi, S, Peeters, Ph, Berrino, F, Dossus, L, Biessy, C, Olsen, A, Tjonneland, A, Overvad, K, CLAVEL CHAPELON, F, BOUTRON RUAULT, Mc, Tehard, B, Nagel, G, Linseisen, J, Boeing, H, Lahmann, Ph, Trichopoulou, A, Trichopoulos, D, Koliva, M, Palli, D, Panico, Salvatore, Tumino, R, Sacerdote, C, VAN GILS, Ch, VAN NOORD, P, Grobbee, De, BUENO DE MESQUITA, Hb, Gonzalez, Ca, Agudo, A, Chirlaque, Md, Barricarte, A, Larranaga, N, Quiros, Jr, Bingham, S, Khaw, Kt, Key, T, Allen, Ne, Lukanova, A, Slimani, N, Saracci, R, Riboli, E, and Kaaks, R.
Subjects: Adult, Cancer Research, medicine.medical_specialty, Colorectal cancer, Endocrinology, Diabetes and Metabolism, Breast Neoplasms, chemistry.chemical_compound, Endocrinology, Breast cancer, Risk Factors, medicine, Humans, Nutritional Physiological Phenomena, ddc:610, Insulin-Like Growth Factor I, Prospective cohort study, Gynecology, business.industry, Obstetrics, C-peptide, Incidence, Cancer, Odds ratio, Middle Aged, medicine.disease, Confidence interval, European Prospective Investigation into Cancer and Nutrition, Europe, Insulin-Like Growth Factor Binding Protein 3, Oncology, chemistry, Case-Control Studies, Female, business
Abstract: Blood concentrations of insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) have recently been associated with breast cancer risk, notably in women who developed breast cancer at a young age. Prospective studies published so far, however, were relatively small and odds ratio (OR) estimates imprecise. We present the results of a large prospective case-control study nested within the European Prospective Investigation into Cancer and Nutrition on total IGF-I, IGFBP-3 and breast cancer risk including 1081 incident cases of invasive breast cancer and 2098 matched control subjects. Increasing IGF-I and IGFBP-3 concentrations were associated with a significant increase in breast cancer risk in women who developed breast cancer after 50 years of age (highest vs lowest quintile OR 1.38 (95% confidence interval (CI) 1.02–1.86), P = 0.01, and 1.44 (95% CI 1.04–1.98), P = 0.01, respectively), but no relationship was observed in younger women (OR = 1.03 (95% CI 0.60–1.77), P = 0.81 for IGF-I, and OR = 0.92 (95% CI 0.50–1.70), P = 0.69 for IGFBP-3). There was, however, significant heterogeneity in the relationship of breast cancer with serum IGF-I and IGFBP-3 levels depending on the time interval between blood donation and tumor diagnosis. A reduction in breast cancer risk with increasing IGF-I concentrations was observed in cases with a diagnosis of cancer less than 2 years after blood donation, (OR = 0.76 (95% CI 0.57–1.03)), while an increase in risk was observed for women with a later diagnosis (above or equal to two years after blood collection, OR = 1.51 (95% CI 1.19–1.91)). A similar pattern was observed for IGFBP-3. This study confirms previous findings for an association of serum IGF-I and IGFBP-3 concentrations with breast cancer risk, particularly for women with a later diagnosis of cancer, but it does not support the hypothesis of an involvement of IGF-I in younger women.

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