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151. Factors associated with serum ferritin levels and iron excess: results from the EPIC-EurGast study

Author: Lucía Rizzolo, Victoria Arija, Carlotta Sacerdote, Tilman Kühn, Antonio Agudo, Pilar Amiano, Nasser Laouali, Domenico Palli, Daniel A. Quintana Pacheco, Ramón Quirós, Carmen Santiuste, Emily Sonestedt, Isabel Drake, Elisabete Weiderpass, Lucía Iglesias-Vázquez, Rosario Tumino, Núria Aranda, P Jakszyn, Matthias B. Schulze, Amanda J. Cross, Elom K. Aglago, Eva Ardanaz, Maria Santucci de Magistris, and Daniel Redondo-Sánchez
Subjects: Male, Multivariate analysis, Iron Overload, ALCOHOL-CONSUMPTION, Iron, Medicine (miscellaneous), Physiology, Type 2 diabetes, Overweight, Systemic inflammation, Serum ferritin, DIETARY, medicine, Humans, HFE C282Y, BODY IRON, Hemochromatosis Protein, RISK, Science & Technology, Nutrition and Dietetics, Nutrition & Dietetics, DANISH MEN, business.industry, Iron status, Histocompatibility Antigens Class I, OVERLOAD, Cancer, Middle Aged, medicine.disease, CANCER, Obesity, PHYSICAL-ACTIVITY, Diabetes Mellitus, Type 2, Case-Control Studies, Ferritins, Red meat, 1111 Nutrition and Dietetics, Excess iron, Female, Hemochromatosis, medicine.symptom, business, EPIC, Life Sciences & Biomedicine
Abstract: Purpose Excess iron is involved in the development of non-communicable diseases such as cancer, type 2 diabetes and cardiovascular conditions. We aimed to describe the prevalence of excess iron and its determinants in healthy European adults. Methods Sociodemographic, lifestyle, iron status, dietary information, and HFE genotyping were obtained from controls from the nested case–control study EPIC-EurGast study. High sensitivity C-reactive protein (hsCRP) was measured to address possible systemic inflammation. Descriptive and multivariate analyses were used to assess iron status and its determinants. Results Out of the 828 participants (median age: 58.7 years), 43% were females. Median serum ferritin and prevalence of excess iron were 143.7 µg/L and 35.2% in males, respectively, and 77 µg/L and 20% in females, both increasing with latitude across Europe. Prevalence of HFE C282Y mutation was significantly higher in Northern and Central Europe (~ 11%) than in the South (5%). Overweight/obesity, age, and daily alcohol and heme iron intake were independent determinants for iron status, with sex differences even after excluding participants with hsCRP > 5 mg/L. Obese males showed a greater consumption of alcohol, total and red meat, and heme iron, compared with those normal weight. Conclusion Obesity, higher alcohol and heme iron consumption were the main risk factors for excess iron in males while only age was associated with iron overload in females. Weight control and promoting healthy lifestyle may help prevent iron overload, especially in obese people. Further research is needed to clarify determinants of excess iron in the healthy adult population, helping to reduce the associated comorbidities.
Published: 2021

152. Combining individual and aggregated data to investigate the role of socioeconomic disparities on cancer burden in Italy

Author: Maura Mezzetti, Domenico Palli, and Francesca Dominici
Subjects: Male, Statistics and Probability, Lung Neoplasms, multiple imputation, Inequality, Epidemiology, Computer science, media_common.quotation_subject, Breast Neoplasms, 01 natural sciences, Article, 010104 statistics & probability, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Neoplasms, Econometrics, Cancer burden, Humans, Computer Simulation, 030212 general & internal medicine, 0101 mathematics, Socioeconomic status, ecological inference, media_common, breast and lung cancer, socioeconomic disparity, Confounding, Aggregate (data warehouse), Health Status Disparities, Binomial Distribution, Italy, Socioeconomic Factors, Income, Regression Analysis, Female, Settore SECS-S/01, Algorithms
Abstract: Quantifying socio-economic disparities and understanding the roots of inequalities are growing topics in cancer research, however socio-economic differences are challenging to investigate mainly due to the lack of accurate data at individual-level, while aggregate indicators are only partially informative. We implemented a multiple imputation algorithm within a statistical matching framework that combines diverse sources of data to estimate individual-level associations between income and risk of breast and lung cancer, adjusting for potential confounding factors in Italy. The framework we developed is computationally flexible to be adapted to similar contexts.
Published: 2019

153. Autoimmunity plays a role in the onset of diabetes after 40 years of age

Author: Vittorio Krogh, Rudolf Kaaks, Yvonne T. van der Schouw, Gianluca Severi, Eva Ardanaz, Marc J. Gunter, Tilman Kühn, Nicholas J. Wareham, Timothy J. Key, Francesca Mancini, Carlotta Sacerdote, María José Sánchez, Heiner Boeing, Annemieke M.W. Spijkerman, Peter M. Nilsson, Guy Fagherazzi, Miren Dorronsoro, María Dolores Chirlaque, Kay-Tee Khaw, Olov Rolandsson, Stephen J. Sharp, Salvatore Panico, Domenico Palli, Nita G. Forouhi, Christiane S. Hampe, Claudia Langenberg, Kim Overvad, Rosario Tumino, Elio Riboli, 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), LSHM_CT_2006_037197 N∫ 6236 National Institutes of Health, NIH: DK26190 Compagnia di San Paolo Kræftens Bekæmpelse, DCS German Cancer Research Center, DKFZ Medical Research Council, MRC: MC_UU_12015/1, MC_UU_12015/5, MR/N003284/1 Cancer Research UK, CRUK World Cancer Research Fund, WCRF Bundesministerium für Bildung und Forschung, BMBF Västerbotten Läns Landsting Ministerie van Volksgezondheid, Welzijn en Sport, VWS Agentschap NL: IGE05012 Vetenskapsrådet, VR Umeå Universitet Bundesministerium für Forschung und Technologie, BMFT Deutsche Krebshilfe Bundesministerium fÃ¼r Bildung und Frauen, BMBF Stichting Diabetes Onderzoek Nederland NIHR Imperial Biomedical Research Centre, BRC NIHR Cambridge Biomedical Research Centre: IS-BRC-1215-20014, O. Rolandsson: The Västerboten County Council, M. Dorronsoro: We thank the participants of the Spanish EPIC cohort for their contribution to the study as well as to the team of trained nurses who participated in the recruitment, R. Kaaks: German Cancer Aid, German Ministry of Research (BMBF), K. T. Khaw: Medical Research Council UK, Cancer Research UK, T. Kühn: German Cancer Aid, German Cancer Research Center (DKFZ), German Federal Ministry of Education and Research (BMBF), S. Panico: Compagnia di San Paolo, A. M. W. Spijkerman: EPIC Bilthoven and Utrecht acknowledge the Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), Statistics Netherlands (the Netherlands), EPIC Ragusa acknowledges for their participation blood donors of AVIS-Ragusa (local blood donors association), Y. T. van der Schouw: EPIC Bilthoven and Utrecht acknowledge the Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), Dutch ZON (Zorg Onderzoek Nederland), WCRF, Statistics Netherland, E. Riboli: Imperial College Biomedical Research Centre., Open access funding provided by Umea University. Funding for the InterAct project was provided by the EU FP6 Programme (grant number LSHM_CT_2006_037197). The autoantibody measurement was funded by Västerbotten County Council and Umeå University, Sweden (OR), the National Institutes of Health (DK26190) (CSH) and the Medical Research Council (MC_UU_12015/1) (NJW). OR: the Västerbotten County Council, Umeå University, MDC: Health Research Fund (FIS) of the Spanish Ministry of Health, Murcia Regional Government (N∫ 6236), EA: the Health Research Fund (FIS) of the Spanish Ministry of Health and Navarre Regional Government, RK: German Cancer Aid, the German Ministry of Research (BMBF), TJK: Cancer Research UK, KTK: the Medical Research Council UK, Cancer Research UK, PMN: the Swedish Research Council, KO: the Danish Cancer Society, SP: Compagnia di San Paolo, AMWS: the Dutch Ministry of Public Health, Welfare and Sports (VWS), the Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands, RT: AIRE-ONLUS Ragusa, AVIS-Ragusa, Sicilian Regional Government, AMWS: LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), YTvdS: verification of diabetes cases was additionally funded by NL Agency grant IGE05012 and an Incentive Grant from the Board of the UMC Utrecht, LK Research Funds, Dutch Prevention Funds, NGF: MRC core support (MC_UU_12015/5), NIHR Cambridge Biomedical Research Centre (IS-BRC-1215-20014). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Acknowledgements, We thank all EPIC participants and staff for their contribution to this study. We thank N. Kerrison (MRC Epidemiology Unit, Cambridge, UK) for managing the data and the laboratory team at the MRC Epidemiology Unit, Cambridge for managing the blood samples for the EPIC-InterAct project. We thank the participants of the Spanish EPIC cohort for their contribution to the study as well as the team of trained nurses who participated in the recruitment. O. Rolandsson: The V?sterboten County Council, T. K?hn: German Cancer Aid, German Cancer Research Center (DKFZ), German Federal Ministry of Education and Research (BMBF), E. Riboli: Imperial College Biomedical Research Centre. Some of the data were presented as an abstract at the 54th EASD Annual Meeting in 2018., Rolandsson, Olov [0000-0002-1341-6828], and Apollo - University of Cambridge Repository
Subjects: Male, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Autoimmunity, Type 2 diabetes, medicine.disease_cause, LADA, Endocrinology, Autoantibody, 0302 clinical medicine, POPULATION, RISK, 0303 health sciences, Glutamate Decarboxylase, ANTIBODY POSITIVITY, GAD, Middle Aged, Phenotype, Genetic risk score, Pathophysiology, 3. Good health, Diabetes and Metabolism, Type 1 diabetes, Endokrinologi och diabetes, Female, Life Sciences & Biomedicine, Adult, 030209 endocrinology & metabolism, Endocrinology and Diabetes, Antibodies, Article, 1117 Public Health and Health Services, Endocrinology & Metabolism, 03 medical and health sciences, GLUTAMIC-ACID DECARBOXYLASE, Insulin resistance, Diabetes mellitus, Internal Medicine, medicine, Humans, TYPE-1, Aged, 030304 developmental biology, Science & Technology, business.industry, RECOGNITION, 1103 Clinical Sciences, ADULTS, medicine.disease, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Incident diabetes, Case-Control Studies, Immunology, 1114 Paediatrics and Reproductive Medicine, AUTOANTIBODIES, indident diabetes, business
Abstract: Aims/hypothesis Type 1 and type 2 diabetes differ with respect to pathophysiological factors such as beta cell function, insulin resistance and phenotypic appearance, but there may be overlap between the two forms of diabetes. However, there are relatively few prospective studies that have characterised the relationship between autoimmunity and incident diabetes. We investigated associations of antibodies against the 65 kDa isoform of GAD (GAD65) with type 1 diabetes and type 2 diabetes genetic risk scores and incident diabetes in adults in European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct, a case-cohort study nested in the EPIC cohort. Methods GAD65 antibodies were analysed in EPIC participants (over 40 years of age and free of known diabetes at baseline) by radioligand binding assay in a random subcohort (n = 15,802) and in incident diabetes cases (n = 11,981). Type 1 diabetes and type 2 diabetes genetic risk scores were calculated. Associations between GAD65 antibodies and incident diabetes were estimated using Prentice-weighted Cox regression. Results GAD65 antibody positivity at baseline was associated with development of diabetes during a median follow-up time of 10.9 years (HR for GAD65 antibody positive vs negative 1.78; 95% CI 1.43, 2.20) after adjustment for sex, centre, physical activity, smoking status and education. The genetic risk score for type 1 diabetes but not type 2 diabetes was associated with GAD65 antibody positivity in both the subcohort (OR per SD genetic risk 1.24; 95% CI 1.03, 1.50) and incident cases (OR 1.97; 95% CI 1.72, 2.26) after adjusting for age and sex. The risk of incident diabetes in those in the top tertile of the type 1 diabetes genetic risk score who were also GAD65 antibody positive was 3.23 (95% CI 2.10, 4.97) compared with all other individuals, suggesting that 1.8% of incident diabetes in adults was attributable to this combination of risk factors. Conclusions/interpretation Our study indicates that incident diabetes in adults has an element of autoimmune aetiology. Thus, there might be a reason to re-evaluate the present subclassification of diabetes in adulthood.
Published: 2019

154. Associations of dairy product consumption with mortality in the European Prospective Investigation into Cancer and Nutrition (EPIC)–Italy cohort

Author: Fulvio Ricceri, Giovanna Masala, Francesca Fasanelli, Sara Grioni, Domenico Palli, Valeria Pala, Sabina Sieri, Graziella Frasca, Salvatore Panico, Paolo Chiodini, Rosario Tumino, Claudia Agnoli, Amalia Mattiello, Vittorio Krogh, Pala, Valeria, Sieri, Sabina, Chiodini, Paolo, Masala, Giovanna, Palli, Domenico, Mattiello, Amalia, Panico, Salvatore, Tumino, Rosario, Frasca, Graziella, Fasanelli, Francesca, Ricceri, Fulvio, Agnoli, Claudia, Grioni, Sara, and Krogh, Vittorio
Subjects: Medicine (miscellaneous), Disease, 03 medical and health sciences, 0302 clinical medicine, cardiovascular disease, Cause of Death, Neoplasms, Environmental health, cancer, Animals, Humans, Medicine, Prospective Studies, 030212 general & internal medicine, Product (category theory), Proportional Hazards Models, Consumption (economics), EPIC-Italy, Nutrition and Dietetics, business.industry, Proportional hazards model, Confounding, Cancer, Middle Aged, dairy product consumption, medicine.disease, mortality, Cardiovascular Diseases, Milk, Dairy Products, European Prospective Investigation into Cancer and Nutrition, 030220 oncology & carcinogenesis, Cohort, business
Abstract: Background The relation of dairy product consumption to health and mortality is controversial. Objectives We investigated associations of consumption of various dairy products with mortality in the Italian cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Italy study. Methods Dairy product consumption was assessed by validated semiquantitative FFQs. Multivariable Cox models stratified by center, age, and sex and adjusted for confounders estimated associations of milk (total, full fat, and reduced fat), yogurt, cheese, butter, and dairy calcium consumption with mortality for cancer, cardiovascular disease, and all causes. Nonlinearity was tested by restricted cubic spline regression. Results After a median follow-up of 14.9 y, 2468 deaths were identified in 45,009 participants: 59% from cancer and 19% from cardiovascular disease. No significant association of consumption of any dairy product with mortality was found in the fully adjusted models. A 25% reduction in risk of all-cause mortality was found for milk intake from 160 to 120 g/d (HR: 0.75; 95% CI: 0.61, 0.91) but not for the highest (>200 g/d) category of intake (HR: 0.95; 95% CI: 0.84, 1.08) compared with nonconsumption. Associations of full-fat and reduced-fat milk consumption with all-cause and cause-specific mortality were similar to those for milk as a whole. Conclusions In this Italian cohort characterized by low to average milk consumption, we found no evidence of a dose-response association between milk consumption and mortality and also no association of consumption of other dairy products investigated with mortality.
Published: 2019

155. Exogenous hormone use and cutaneous melanoma risk in women: The European Prospective Investigation into Cancer and Nutrition

Author: Salma Butt, Rudolf Kaaks, Agnès Fournier, Marina Kvaskoff, Elisabete Weiderpass, Karolin Isaksson, Matthias B. Schulze, Susana Merino, Reza Ghiasvand, Gianluca Severi, Eva Ardanaz, Ingrid Ljuslinder, Yahya Mahamat-Saleh, Bas Bueno-de-Mesquita, Renée T. Fortner, Sandra Colorado-Yohar, Marie Al Rahmoun, Salvatore Panico, Clio Dessinioti, Sabina Sieri, Carlotta Sacerdote, Antonia Trichopoulou, Katerina Niforou, Anne Tjønneland, Laure Dossus, Ruth C. Travis, Saverio Caini, Leire Gil Majuelo, Kay-Tee Khaw, Maria J. Sánchez, Marit B. Veierød, Anja Olsen, Sabina Rinaldi, Torkjel M. Sandanger, Iris Cervenka, Malin Jansson, Marie-Christine Boutron-Ruault, Rosario Tumino, Edoardo Botteri, Domenico Palli, and Leila Lujan-Barroso
Subjects: Oncology, Cancer Research, Skin Neoplasms, Time Factors, Dones, hormonal treatments, 030207 dermatology & venereal diseases, 0302 clinical medicine, cohort studies, Risk Factors, Surveys and Questionnaires, Epidemiology, Skin cancer, Medicine, Prospective Studies, Prospective cohort study, Melanoma, oral contraceptives, Incidence, Estrogen Replacement Therapy, Confounding, Hazard ratio, Confounding Factors, Epidemiologic, Middle Aged, European Prospective Investigation into Cancer and Nutrition, Europe, Postmenopause, 030220 oncology & carcinogenesis, epidemiology, Female, Cohort study, Adult, medicine.medical_specialty, menopausal hormone therapy, Contraceptives, Oral, Hormonal, cutaneous melanoma, 03 medical and health sciences, Breast cancer, Internal medicine, Humans, VDP::Medisinske Fag: 700, Women, Nutrició, Càncer de pell, Aged, Proportional Hazards Models, Nutrition, business.industry, medicine.disease, VDP::Medical disciplines: 700, Premenopause, Cutaneous melanoma, business
Abstract: This is the peer reviewed version of the following article: Cervenka, I., Al Rahmoun, M., Mahamat-Saleh, Y., Fournier, A., Boutron-Ruault, M.-C., Severi, G. ... Kvaskoff, M. (2019). Exogenous hormone use and cutaneous melanoma risk in women: The European Prospective Investigation into Cancer and Nutrition. International Journal of Cancer, which has been published in final form at https://doi.org/10.1002/ijc.32674. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. Evidence suggests an influence of sex hormones on cutaneous melanoma risk, but epidemiologic findings are conflicting. We examined the associations between use of oral contraceptives (OCs) and menopausal hormone therapy (MHT) and melanoma risk in women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a prospective cohort study initiated in 1992 in 10 European countries. Information on exogenous hormone use at baseline was derived from country‐specific self‐administered questionnaires. We used Cox proportional hazards regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Over 1992–2015, 1,696 melanoma cases were identified among 334,483 women, whereof 770 cases among 134,758 postmenopausal women. There was a positive, borderline‐significant association between OC use and melanoma risk (HR = 1.12, 95% CI = 1.00–1.26), with no detected heterogeneity across countries (phomogeneity = 0.42). This risk increased linearly with duration of use (ptrend = 0.01). Among postmenopausal women, ever use of MHT was associated with a nonsignificant increase in melanoma risk overall (HR = 1.14, 95% CI = 0.97–1.43), which was heterogeneous across countries (phomogeneity = 0.05). Our findings do not support a strong and direct association between exogenous hormone use and melanoma risk. In order to better understand these relations, further research should be performed using prospectively collected data including detailed information on types of hormone, and on sun exposure, which may act as an important confounder or effect modifier on these relations.
Published: 2019

156. Education and gastric cancer risk—An individual participant data meta‐analysis in the StoP project consortium

Author: Kenneth C. Johnson, Rossella Bonzi, Matteo Rota, Stefania Boccia, Nerea Fernández de Larrea, Robert C. Kurtz, Claudio Pelucchi, Nuno Lunet, Niclas Håkansson, Pagona Lagiou, Joshua E. Muscat, Gianfranco Alicandro, Carlo La Vecchia, Guo Pei Yu, Domenico Palli, David Zaridze, Reza Malekzadeh, Ana Ferro, Malaquías López-Cervantes, Weimin Ye, Mohammadreza Pakseresht, Paolo Boffetta, Lina Mu, Areti Lagiou, Zuo-Feng Zhang, Shoichiro Tsugane, Jesús Vioque, Amelie Plymoth, Paola Bertuccio, Eva Negri, Manolis Kogevinas, Gerson Shigeaki Hamada, Akihisa Hidaka, Carlotta Galeone, Raúl U. Hernández-Ramírez, Mary H. Ward, Jinfu Hu, Dmitry Maximovitch, Farhad Pourfarzi, Eva María Navarrete-Muñoz, Lizbeth López-Carrillo, Alicja Wolk, Monica Ferraroni, Rota M., Alicandro G., Pelucchi C., Bonzi R., Bertuccio P., Hu J., Zhang Z.-F., Johnson K.C., Palli D., Ferraroni M., Yu G.-P., Galeone C., Lopez-Carrillo L., Muscat J., Lunet N., Ferro A., Ye W., Plymoth A., Malekzadeh R., Zaridze D., Maximovitch D., Kogevinas M., Fernandez de Larrea N., Vioque J., Navarrete-Munoz E.M., Tsugane S., Hamada G.S., Hidaka A., Pakseresht M., Wolk A., Hakansson N., Hernandez-Ramirez R.U., Lopez-Cervantes M., Ward M., Pourfarzi F., Mu L., Kurtz R.C., Lagiou A., Lagiou P., Boffetta P., Boccia S., Negri E., La Vecchia C., and Instituto de Saúde Pública da Universidade do Porto
Subjects: Male, Cancer Research, Datasets as Topic, socioeconomic inequalitie, 0302 clinical medicine, risk factors, Medicine, education, gastric cancer, income, risk factors, socioeconomic inequalities, education, education.field_of_study, socioeconomic inequalities, Incidence, Incidence (epidemiology), Relative index of inequality, Middle Aged, Europe, income, Oncology, 030220 oncology & carcinogenesis, Meta-analysis, Educational Status, Female, Case-Control Studie, Human, Adult, Asia, Population, Vulnerable Population, Risk Assessment, Vulnerable Populations, Helicobacter Infections, 03 medical and health sciences, Stomach Neoplasm, Stomach Neoplasms, Humans, Risk factor, Settore MED/42 - IGIENE GENERALE E APPLICATA, Aged, Helicobacter pylori, business.industry, Risk Factor, gastric cancer, Health Status Disparities, Odds ratio, Educational Statu, Confidence interval, Gastric Mucosa, Case-Control Studies, North America, Household income, business, Helicobacter Infection, Demography
Abstract: Low socioeconomic position (SEP) is a strong risk factor for incidence and premature mortality from several cancers. Our study aimed at quantifying the association between SEP and gastric cancer (GC) risk through an individual participant data meta-analysis within the “Stomach cancer Pooling (StoP) Project”. Educational level and household income were used as proxies for the SEP. We estimated pooled odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) across levels of education and household income by pooling study-specific ORs through random-effects meta-analytic models. The relative index of inequality (RII) was also computed. A total of 9,773 GC cases and 24,373 controls from 25 studies from Europe, Asia and America were included. The pooled OR for the highest compared to the lowest level of education was 0.60 (95% CI, 0.44–0.84), while the pooled RII was 0.45 (95% CI, 0.29–0.69). A strong inverse association was observed both for noncardia (OR 0.39, 95% CI, 0.22–0.70) and cardia GC (OR 0.47, 95% CI, 0.22–0.99). The relation was stronger among H. pylori negative subjects (RII 0.14, 95% CI, 0.04–0.48) as compared to H. pylori positive ones (RII 0.29, 95% CI, 0.10–0.84), in the absence of a significant interaction (p = 0.28). The highest household income category showed a pooled OR of 0.65 (95% CI, 0.48–0.89), while the corresponding RII was 0.40 (95% CI, 0.22–0.72). Our collaborative pooled-analysis showed a strong inverse relationship between SEP indicators and GC risk. Our data call for public health interventions to reduce GC risk among the more vulnerable groups of the population. This project was supported by the “Associazione Italiana per la Ricerca sul Cancro” (AIRC), Projects no. 16715 and 21378 (Investigator Grant), by the “Fondazione Italiana per la Ricerca sul Cancro” (FIRC) and by the Italian Ministry of Health (Young Researchers, GR-2011-02347943 to SB). MR is grateful to the FIRC who supported his work from 2015 to 2017. Our study was also funded by FEDER through the Operational Programme Competitiveness and Internationalization and national funding from the Foundation for Science and Technology – FCT (Portuguese Ministry of Science, Technology and Higher Education) under the Unidade de Investigação em Epidemiologia – Instituto de Saúde Pública da Universidade do Porto (EPIUnit; POCI-01-0145-FEDER-006862; Ref. UID/DTP/04750/2013). AF (PD/BD/105823/2014) was awarded an individual scholarship through national funding from FCT/MCTES.
Published: 2019

157. The risk of extra-ovarian malignancies among women with endometriosis: A systematic literature review and meta-analysis

Author: Matteo Lazzeroni, Saverio Caini, Giovanna Masala, Calogero Saieva, Fedro A. Peccatori, Domenico Palli, Benedetta Bendinelli, and Sara Gandini
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, Endometriosis, Breast Neoplasms, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Risk Factors, Internal medicine, medicine, Humans, Melanoma, Cervical cancer, business.industry, Endometrial cancer, Hematology, Publication bias, medicine.disease, 030104 developmental biology, 030220 oncology & carcinogenesis, Meta-analysis, Relative risk, Female, business, Cohort study
Abstract: We conducted a meta-analysis of studies reporting on the risk of extra-ovarian malignancies among women with endometriosis. Summary relative risk (SRR) and 95% confidence intervals (CI) were calculated through random effect models. We explored causes of between-studies heterogeneity and assessed the presence of publication bias. We included 32 studies published between 1989 and 2018. We found an increased risk of endometrial (SRR 1.38, 95%CI 1.10-1.74) and thyroid cancer (SRR 1.38, 95%CI 1.17-1.63), and inverse association with cervical cancer (SRR 0.78, 95%CI 0.60-0.95). No association emerged for breast cancer (SRR 1.04, 95%CI 0.99-1.09) and melanoma (SRR 1.31, 95%CI 0.86-1.96). Between-study heterogeneity was large for breast and endometrial cancer and melanoma. Associations were generally stronger in case-control, cross-sectional, and cohort studies with internal control group, compared to cohort studies with external control group. No indication for publication bias was found. Our conclusions need to be confirmed in properly designed cohort studies with clinical confirmation of endometriosis.
Published: 2019

158. Novel Common Genetic Susceptibility Loci for Colorectal Cancer

Author: Katja Butterbach, Julyann Pérez-Mayoral, Douglas F. Easton, Stefanie Brezina, Ben Zhang, Frank J. Manion, Hansong Wang, Sanford D. Markowitz, Liesel M. FitzGerald, Sun Ha Jee, Michelle Cotterchio, Daniel D. Buchanan, Timothy R. Church, Wolfgang Lieb, Xiao-Ou Shu, John L. Hopper, Stephanie A. Bien, Manuela Gago-Dominguez, Jian Gong, Laurence N. Kolonel, Graham G. Giles, Leon Raskin, Yingchang Lu, Kristen Anton, Charles S. Fuchs, Fränzel J.B. van Duijnhoven, Hermann Brenner, Yi Lin, Clicerio Gonzalez-Villalpando, Yong-Bing Xiang, Aaron K. Aragaki, Daniela Seminara, Stephanie M. Gogarten, Gad Rennert, Jose E. Castelao, Rocky Fischer, Antonio J. Molina, Jarmo Virtamo, Tabitha A. Harrison, Volker Arndt, Lee Soo Chin, Michael Hoffmeister, Mark A. Jenkins, Shu Chen Huang, Chris S. Carlson, Stéphane Bézieau, Rebecca D. Jackson, Bhramar Mukherjee, Darin Taverna, Bridget M. Riggs, Christopher K. Edlund, Christopher A. Haiman, Melissa C. Southey, Anna H. Wu, Marilena Melas, Antonia Trichopoulou, Hedy S. Rennert, Gianluca Severi, Stephen B. Gruber, Noralane M. Lindor, Gerhard A. Coetzee, Richard B. Hayes, Sarah J. Plummer, Keitaro Matsuo, Mathieu Lemire, Philipp Hofer, Neil Murphy, José María Huerta, Paul D.P. Pharoah, Erin M. Siegel, Sébastien Küry, Thomas J. Hudson, Annika Lindblom, Marcia Cruz Correa, Michael O. Woods, Sophia Harlid, Tilman Kuehn, David Shibata, Christopher I. Li, Stephen N. Thibodeau, Stephen J. Chanock, Jochen Hampe, Flavio Lejbkowicz, Jeroen R. Huyghe, Suminori Kono, Jenny Chang-Claude, Aung Ko Win, Brent W. Zanke, Alicja Wolk, David V. Conti, Elena M. Gonzalez-Villalpando, Christopher I. Amos, Shuo Jiao, Domenico Palli, Vicente Martín, Jesus P. Paredes Cotoré, Stephanie J. Weinstein, Andrea Gsur, William M. Grady, Koichi Matsuda, Loic Le Marchand, Hanane Omichessan, Marc J. Gunter, Graham Casey, Li Li, Zsofia K. Stadler, Eric J. Jacobs, Kevin McDonnell, Dallas R. English, Demetrius Albanes, Amit Joshi, Wei Zheng, Mariana C. Stern, Cecelia A. Laurie, Jing Ma, Cornelia M. Ulrich, Stephanie L. Schmit, Victor Moreno, John D. Potter, Chenxu Qu, Bette J. Caan, Heinz-Josef Lenz, M. Henar Alonso, Andrea Z. LaCroix, Christoph Mancao, John F. Harju, Yun Ru Liu, Jane C. Figueiredo, Gregory Idos, Kana Wu, Duncan C. Thomas, Motoki Iwasaki, W. James Gauderman, Thomas A. Sellers, David Van Den Berg, Barbara K. Fortini, David N. Levine, James M. Church, Ya Wen Cheng, Edith J. M. Feskens, Edward Giovannucci, Manish Gala, Polly A. Newcomb, Charles Kooperberg, Iona Cheng, David J. Hunter, Martha L. Slattery, Roger L. Milne, Lars G. Fritsche, Niha Zubair, Steven Gallinger, Yi Xin Zeng, Wei Shi, Andrew T. Chan, Fotios Loupakis, Vittorio Krogh, Clemens Schafmayer, Sun-Seog Kweon, Bethany van Guelpan, Amanda Bloomer, Kenneth Offit, Stephanie Tring, Shoichiro Tsugane, David Duggan, Fredrick R. Schumacher, Joseph Vijai, Weihua Jia, Marie-Christine Boutron-Ruault, Joel K. Greenson, Frank Luh, Ulrike Peters, Keith R. Curtis, Juergen Boehm, Robert E. Schoen, Sonja I. Berndt, Elizabeth L. Barry, Sebastian Stintzing, Li Hsu, Emily White, Conghui Qu, Peter T. Campbell, Caroline McNeil, and Yun Yen
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Genotype, Nutrition and Disease, Colorectal cancer, Genome-wide association study, Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, 0302 clinical medicine, Càncer colorectal, Internal medicine, Voeding en Ziekte, Ethnicity, medicine, Genetic predisposition, Genetics, Humans, Life Science, Genetic Predisposition to Disease, Oncology & Carcinogenesis, Allele, Allele frequency, Genetic association, VLAG, Global Nutrition, Wereldvoeding, Oncology And Carcinogenesis, Case-control study, Articles, Prognosis, medicine.disease, United States, 3. Good health, Genetic Loci, Case-Control Studies, 030220 oncology & carcinogenesis, Colorectal Neoplasms, Genètica, Follow-Up Studies, Genome-Wide Association Study
Abstract: Background Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10−8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk. Methods We conducted a GWAS in European descent CRC cases and control subjects using a discovery–replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10−8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided. Results The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10−8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0. Conclusions This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screening.
Published: 2019

159. Plasma concentrations of persistent organic pollutants and pancreatic cancer risk

Author: Therese Haugdahl Nøst, Bas Bueno de-Mesquita, Matthias B. Schulze, Carlos A. González, Miguel Rodríguez-Barranco, Àlex Giménez-Robert, Inge Huybrechts, Ingvar A. Bergdahl, Eric J. Duell, Rudolf Kaaks, Sara Grioni, Juan Alguacil, Carolina Donat-Vargas, Anne Tjønneland, Neil Murphy, Ole Raaschou-Nielsen, Elio Riboli, Veronique Chajes, Alessio Naccarati, A. Agudo, J. Ramón Quirós, Maria-Dolores Chirlaque, Miquel Porta, Eva Ardanaz, Lluís Cirera, Francesca Mancini, Kim Overvad, Vinciane Rebours, Magda Gasull, Elisabete Weiderpass, Fernando Goñi-Irigoyen, Nicholas J. Wareham, José Pumarega, Malin Sund, Verena Katzke, Sandra Colorado-Yohar, Mattias Johansson, Antonia Trichopoulou, Roel Vermeulen, Alicia K Heath, Pietro Ferrari, Timothy J. Key, Dagfinn Aune, Marie-Christine Boutron-Ruault, Torkjel M. Sandanger, Rosario Tumino, Charlotta Rylander, Hannu Kiviranta, Paolo Vineis, Salvatore Panico, Marc J. Gunter, Panu Rantakokko, Domenico Palli, Porta, Miquel [0000-0003-1684-7428], Vineis, Paolo [0000-0001-8935-4566], Apollo - University of Cambridge Repository, Department of Surgery, and HUS Abdominal Center
Subjects: 0301 basic medicine, medicine.medical_specialty, Epidemiology, pancreatic cancer, environmental health, persistent organic pollutants, 1117 Public Health and Health Services, methods, CHEMICALS, Arbetsmedicin och miljömedicin, 03 medical and health sciences, Persistent Organic Pollutants, 0302 clinical medicine, Pancreatic cancer, Internal medicine, medicine, Humans, EXPOSURE, Pesticides, Public, Environmental & Occupational Health, Science & Technology, business.industry, 0104 Statistics, biomarkers, Public Health, Global Health, Social Medicine and Epidemiology, Occupational Health and Environmental Health, ORGANOCHLORINE COMPOUNDS, Pancreatic Neoplasms/epidemiology, General Medicine, Odds ratio, medicine.disease, Polychlorinated Biphenyls, Confidence interval, European Prospective Investigation into Cancer and Nutrition, Pancreatic Neoplasms, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, 030104 developmental biology, Quartile, 3121 General medicine, internal medicine and other clinical medicine, 030220 oncology & carcinogenesis, Clinical diagnosis, Case-Control Studies, Cohort, Plasma concentration, Environmental Pollutants, business, Life Sciences & Biomedicine
Abstract: Background Findings and limitations of previous studies on persistent organic pollutants (POPs) and pancreatic cancer risk support conducting further research in prospective cohorts. Methods We conducted a prospective case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Participants were 513 pancreatic cancer cases and 1020 matched controls. Concentrations of 22 POPs were measured in plasma collected at baseline. Results Some associations were observed at higher concentrations of p, p’-DDT, trans-nonachlor, β-hexachlorocyclohexane and the sum of six organochlorine pesticides and of 16 POPs. The odds ratio (OR) for the upper quartile of trans-nonachlor was 1.55 (95% confidence interval 1.06-2.26; P for trend = 0.025). Associations were stronger in the groups predefined as most valid (participants having fasted >6 h, with microscopic diagnostic confirmation, normal weight, and never smokers), and as most relevant (follow-up ≥10 years). Among participants having fasted >6 h, the ORs were relevant for 10 of 11 exposures. Higher ORs were also observed among cases with microscopic confirmation than in cases with a clinical diagnosis, and among normal-weight participants than in the rest of participants. Among participants with a follow-up ≥10 years, estimates were higher than in participants with a shorter follow-up (for trans-nonachlor: OR = 2.14, 1.01 to 4.53, P for trend = 0.035). Overall, trans-nonachlor, three PCBs and the two sums of POPs were the exposures most clearly associated with pancreatic cancer risk. Conclusions Individually or in combination, most of the 22 POPs analysed did not or only moderately increased the risk of pancreatic cancer.
Published: 2021

160. No association between polymorphisms in CYP2E1, GSTM1, NAT1, NAT2 and the risk of gastric adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition

Author: Salvatore Panico, Nadia García, H. B. Bueno-De-Mesquita, Kim Overvad, Hendriek C. Boshuizen, Timothy J. Key, M. E. Numans, Antonio Berenguer, Rosario Tumino, Khaw K-T., Gabriele Nagel, Carmen Navarro, Boutron-Ruault M-C., Domenico Palli, Elio Riboli, J. Linseisen, Anne Tjønneland, Aurelio Barricarte, A. Olsen, Eiliv Lund, Françoise Clavel-Chapelon, Calogero Saieva, Teresa Norat, G. Del Giudice, Sheila Bingham, Guillem Pera, Henrik Simán, Antonia Trichopoulou, Mazda Jenab, Carlos A. González, Hendrik Bläker, J. R. Quirós, Carlos Martinez, Antonio Agudo, Roger Stenling, P. H. M. Peeters, Carlotta Sacerdote, Pilar Amiano, Pamela Ferrari, Naomi E. Allen, Göran Berglund, Fátima Carneiro, Gabriel Capellá, Franco Berrino, Heiner Boeing, Núria Sala, and Göran Hallmans
Subjects: Male, Oncology, medicine.medical_specialty, Pathology, Genotype, Arylamine N-Acetyltransferase, Epidemiology, Adenocarcinoma, Biology, Glutathione transferase, Gastric adenocarcinoma, Stomach Neoplasms, Internal medicine, medicine, Humans, Stomach cancer, neoplasms, Glutathione Transferase, Polymorphism, Genetic, integumentary system, Cytochrome P-450 CYP2E1, Middle Aged, medicine.disease, digestive system diseases, European Prospective Investigation into Cancer and Nutrition, Europe, Logistic Models, Case-Control Studies, Female, Stomach Adenocarcinoma
Abstract: No association between polymorphisms in CYP2E1, GSTM1, NAT1, NAT2 and the risk of gastric adenocarcinoma in the European prospective investigation into cancer and nutrition.
Published: 2021

161. Genetically predicted circulating concentrations of micronutrients and risk of colorectal cancer among individuals of European descent:a Mendelian randomization study

Author: Domenico Palli, Marc J. Gunter, Aurora Perez-Cornago, Emily White, Peter T. Campbell, Andrew T. Chan, Lori C. Sakoda, Gad Rennert, Graham Casey, Bethany Van Guelpen, Kala Visvanathan, Loic Le Marchand, Tilman Kühn, David S. Lopez, Anna H. Wu, Amanda J. Cross, Graham G. Giles, P Jakszyn, Hongmei Nan, Sun-Seog Kweon, Stephen B. Gruber, Jenny Chang-Claude, Ulrike Peters, Kimberley Burrows, Linda Snetselaar, Michael Hoffmeister, Bas Bueno-de-Mesquita, Barbara L. Banbury, D. Timothy Bishop, Demetrius Albanes, Georgios Markozannes, Steven Gallinger, John D. Potter, David J. Hunter, Martha L. Slattery, Stephen N. Thibodeau, Wei Zheng, Verena Zuber, Ruth C. Travis, Annika Lindblom, Vicente Martín, Dipender Gill, Sergi Castellví-Bel, Kenneth Offit, Sonja I. Berndt, Temitope O. Keku, Niki Dimou, Ludmila Vodickova, David J. Hughes, Jeanette M. Schenk, Fränzel J.B. Van Duijnhoven, Hansong Wang, Clemens Schafmayer, Cornelia M. Ulrich, Hermann Brenner, Jane C. Figueiredo, Victor Moreno, Timothy J. Key, Juergen Boehm, Richard M. Martin, Paul D.P. Pharoah, Christopher I. Li, Susanna C. Larsson, Stéphane Bézieau, Li Li, Edward Giovannucci, Konstantinos K. Tsilidis, Elizabeth A. Platz, Sarah J Lewis, Volker Arndt, Nikos Papadimitriou, Roger L. Milne, Polly A. Newcomb, Marie-Christine Boutron-Ruault, Alicja Wolk, Sophia Harlid, Jochen Hampe, Heather Hampel, Andrea Gsur, Rami Nassir, Phyllis J. Goodman, Albert de la Chapelle, Neil Murphy, Mark A. Jenkins, Michael O. Woods, Andrea N. Burnett-Hartman, Lihong Qi, Elio Riboli, Centre international de Recherche sur le Cancer (CIRC), Centre hospitalier universitaire de Nantes (CHU Nantes), 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, and Institut Gustave Roussy (IGR)
Subjects: 0301 basic medicine, and promotion of well-being, Nutrition and Disease, Colorectal cancer, [SDV]Life Sciences [q-bio], Medicine (miscellaneous), Medical and Health Sciences, Gastroenterology, Corrections, 09 Engineering, supplements, chemistry.chemical_compound, Engineering, 0302 clinical medicine, Risk Factors, Voeding en Ziekte, Micronutrients, genes, 11 Medical and Health Sciences, Cancer, Nutrition and Dietetics, Micronutrient, Colo-Rectal Cancer, 3. Good health, Original Research Communications, Vitamin B 12, nutrition, ICEP, Colorectal Neoplasms, Vitamin, medicine.medical_specialty, Clinical Trials and Supportive Activities, 030209 endocrinology & metabolism, colorectal cancer, Lower risk, White People, 03 medical and health sciences, Selenium, Clinical Research, Internal medicine, Complementary and Integrative Health, Mendelian randomization, medicine, Vitamin D and neurology, Humans, Genetic Predisposition to Disease, 3.3 Nutrition and chemoprevention, 030109 nutrition & dietetics, Nutrition & Dietetics, business.industry, Prevention, Case-control study, Mendelian Randomization Analysis, Prevention of disease and conditions, medicine.disease, chemistry, Case-Control Studies, Dietary Supplements, Digestive Diseases, business
Abstract: International audience; Background: The literature on associations of circulating concentrations of minerals and vitamins with risk of colorectal cancer is limited and inconsistent. Evidence from randomized controlled trials (RCTs) to support the efficacy of dietary modification or nutrient supplementation for colorectal cancer prevention is also limited. Objectives: To complement observational and RCT findings, we investigated associations of genetically predicted concentrations of 11 micronutrients (β-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B-6, vitamin B-12, and zinc) with colorectal cancer risk using Mendelian randomization (MR). Methods: Two-sample MR was conducted using 58,221 individuals with colorectal cancer and 67,694 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry. Inverse variance-weighted MR analyses were performed with sensitivity analyses to assess the impact of potential violations of MR assumptions. Results: Nominally significant associations were noted for genetically predicted iron concentration and higher risk of colon cancer [ORs per SD (ORSD): 1.08 95% CI: 1.00, 1.17 P value = 0.05] and similarly for proximal colon cancer, and for vitamin B-12 concentration and higher risk of colorectal cancer (ORSD: 1.12 95% CI: 1.03, 1.21 P value = 0.01) and similarly for colon cancer. A nominally significant association was also noted for genetically predicted selenium concentration and lower risk of colon cancer (ORSD: 0.98 95% CI: 0.96, 1.00 P value = 0.05) and similarly for distal colon cancer. These associations were robust to sensitivity analyses. Nominally significant inverse associations were observed for zinc and risk of colorectal and distal colon cancers, but sensitivity analyses could not be performed. None of these findings survived correction for multiple testing. Genetically predicted concentrations of β-carotene, calcium, copper, folate, magnesium, phosphorus, and vitamin B-6 were not associated with disease risk. Conclusions: These results suggest possible causal associations of circulating iron and vitamin B-12 (positively) and selenium (inversely) with risk of colon cancer.
Published: 2021

162. Urinary concentrations of (+)-catechin and (-)-epicatechin as biomarkers of dietary intake of flavan-3-ols in the european prospective investigation into cancer and nutrition (epic) study

Author: Matthias B. Schulze, David Achaintre, Enrique Almanza-Aguilera, Rosario Tumino, Joseph A. Rothwell, Theron Johnson, Verena Katzke, Gianluca Severi, Carlotta Sacerdote, Nasser Laouali, Domenico Palli, Maria Santucci de Magistris, Augustin Scalbert, Raul Zamora-Ros, Daniela Ceballos-Sánchez, Giuliana Gargano, Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), 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, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Universität Potsdam, Università degli studi di Napoli Federico II, Instituto de Salud Carlos III, ISCIII: PI18/00191, European Regional Development Fund, ERDF, Funding: This research was funded by the by the Institute of Health Carlos III through the grant PI18/00191 (co-funded by European Regional Development Fund. ERDF, a way to build Europe), and from the 553/C/2019 project, funded by La Marató de TV-3. The national EPIC cohorts are supported by the French National Cancer Institute (L’Institut National du Cancer, INCA Grant No. 2009-139), 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), German Federal Ministry of Education and Research (Germany), the Hellenic Health Foundation (Greece), Italian Association for Research on Cancer, and Compagnia San Paolo (Italy). IDIBELL acknowledges support from the Generalitat de Catalunya through the CERCA Program. E.A.-A. and R.Z.-R. wish to thank the 'Sara Borrell' (CD20/00071) and the 'Miguel Servet' (CP CPII20/00009) programs from the Institute of Health Carlos III (co-funded by the European Social Fund (ESF)—ESF investing in your future).
Subjects: Male, Questionnaires, 030309 nutrition & dietetics, Urine, Catechin, chemistry.chemical_compound, Eating, Medicine, TX341-641, Food science, Prospective Studies, Epicatechin, 0303 health sciences, Nutrition and Dietetics, Biochemical markers, Middle Aged, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, Proanthocyanidin, Marcadors bioquímics, Intake, Female, Adult, Urinary system, Qüestionaris, Diet Surveys, Article, Statistics, Nonparametric, Flavan-3-ols, 03 medical and health sciences, Herbal tea, Flavan, Biflavonoids, Humans, Proanthocyanidins, 030304 developmental biology, Aged, Wine, Flavonoids, business.industry, Nutrition. Foods and food supply, Orina, Diet, Nutrition Assessment, chemistry, Food, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Aliments, business, EPIC, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Biomarkers, Food Science
Abstract: This study examines the correlation of acute and habitual dietary intake of flavan-3-ol monomers, proanthocyanidins, theaflavins, and their main food sources with the urinary concentrations of (+)-catechin and (-)-epicatechin in the European Prospective Investigation into Cancer and Nutrition study (EPIC). Participants (N = 419, men and women) provided 24-h urine samples and completed a 24-h dietary recall (24-HDR) on the same day. Acute and habitual dietary data were collected using a standardized 24-HDR software and a validated dietary questionnaire, respectively. Intake of flavan-3-ols was estimated using the Phenol-Explorer database. Concentrations of (+)-catechin and (-)-epicatechin in 24-h urine were analyzed using tandem mass spectrometry after enzymatic deconjugation. Simple and partial Spearman’s correlations showed that urinary concentrations of (+)-catechin, (-)-epicatechin and their sum were more strongly correlated with acute than with habitual intake of individual and total monomers (acute rpartial = 0.13–0.54, p &lt, 0.05, and habitual rpartial = 0.14–0.28, p &lt, 0.01), proanthocyanidins (acute rpartial = 0.24–0.49, p &lt, 0.001, and habitual rpartial = 0.10–0.15, p &lt, 0.05), theaflavins (acute rpartial = 0.22–0.31, p &lt, and habitual rpartial = 0.20–0.26, p &lt, 0.01), and total flavan-3-ols (acute rpartial = 0.40–0.48, p &lt, and habitual rpartial = 0.23–0.33, p &lt, 0.001). Similarly, urinary concentrations of flavan-3-ols were weakly correlated with both acute (rpartial = 0.12–0.30, p &lt, 0.05) and habitual intake (rpartial = 0.10–0.27, p &lt, 0.05) of apple and pear, stone fruits, berries, chocolate and chocolate products, cakes and pastries, tea, herbal tea, wine, red wine, and beer and cider. Moreover, all comparable correlations were stronger for urinary (-)-epicatechin than for (+)-catechin. In conclusion, our data support the use of urinary concentrations of (+)-catechin and (-)-epicatechin, especially as short-term nutritional biomarkers of dietary catechin, epicatechin and total flavan-3-ol monomers.
Published: 2021

163. Coffee consumption and gastric cancer: a pooled analysis from the Stomach cancer Pooling Project consortium

Author: Domenico Palli, Manoli García de la Hera, Shoichiro Tsugane, Francesca Bravi, Nuno Lunet, Pagona Lagiou, Jinfu Hu, Stefania Boccia, Monica Ferraroni, Lizbeth López-Carrillo, Areti Lagiou, Vicente Martín, Robert C. Kurtz, Mary H. Ward, Georgia Martimianaki, Eva Negri, Raúl U. Hernández-Ramírez, Kenneth C. Johnson, Anna Karakatsani, Carlo La Vecchia, M Costanza Camargo, Paolo Boffetta, Maria Paula Curado, Paola Bertuccio, Reza Malekzadeh, Zuo-Feng Zhang, Charles S. Rabkin, Akihisa Hidaka, Dmitry Maximovitch, Linda M. Liao, David Zaridze, Jesús Vioque, Rossella Bonzi, Greta Carioli, Gianfranco Alicandro, Nuria Aragonés, Rashmi Sinha, Antonia Trichopoulou, Samantha Morais, Gerson Shigueaki Hamada, Claudio Pelucchi, Martimianaki G., Bertuccio P., Alicandro G., Pelucchi C., Bravi F., Carioli G., Bonzi R., Rabkin C.S., Liao L.M., Sinha R., Johnson K., Hu J., Palli D., Ferraroni M., Lunet N., Morais S., Tsugane S., Hidaka A., Hamada G.S., Lopez-Carrillo L., Hernandez-Ramirez R.U., Zaridze D., Maximovitch D., Aragones N., Martin V., Ward M.H., Vioque J., Garcia De La Hera M., Zhang Z.-F., Kurtz R.C., Lagiou P., Lagiou A., Trichopoulou A., Karakatsani A., Malekzadeh R., Camargo M.C., Curado M.P., Boccia S., Boffetta P., Negri E., and La Vecchia C.
Subjects: Cancer Research, medicine.medical_specialty, Epidemiology, case-control study, Oncology and Carcinogenesis, coffee, Coffee consumption, Article, Stomach Neoplasms, Risk Factors, Clinical Research, Internal medicine, Coffee intake, Odds Ratio, medicine, Humans, Oncology & Carcinogenesis, Stomach cancer, Settore MED/42 - IGIENE GENERALE E APPLICATA, Cancer, coffee consumption, business.industry, gastric cancer, Public Health, Environmental and Occupational Health, cardia cancer, Odds ratio, medicine.disease, Confidence interval, Observational Studies as Topic, Logistic Models, Pooled analysis, Oncology, Public Health and Health Services, pooled analysis, business, Random intercept
Abstract: Objective This study aimed to evaluate and quantify the relationship between coffee and gastric cancer using a uniquely large dataset from an international consortium of observational studies on gastric cancer, including data from 18 studies, for a total of 8198 cases and 21 419 controls. Methods A two-stage approach was used to obtain the pooled odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) for coffee drinkers versus never or rare drinkers. A one-stage logistic mixed-effects model with a random intercept for each study was used to estimate the dose-response relationship. Estimates were adjusted for sex, age and the main recognized risk factors for gastric cancer. Results Compared to never or rare coffee drinkers, the estimated pooled OR for coffee drinkers was 1.03 (95% CI, 0.94-1.13). When the amount of coffee intake was considered, the pooled ORs were 0.91 (95% CI, 0.81-1.03) for drinkers of 1-2 cups per day, 0.95 (95% CI, 0.82-1.10) for 3-4 cups, and 0.95 (95% CI, 0.79-1.15) for five or more cups. An OR of 1.20 (95% CI, 0.91-1.58) was found for heavy coffee drinkers (seven or more cups of caffeinated coffee per day). A positive association emerged for high coffee intake (five or more cups per day) for gastric cardia cancer only. Conclusions These findings better quantify the previously available evidence of the absence of a relevant association between coffee consumption and gastric cancer.
Published: 2021

164. Lifetime alcohol intake, drinking patterns over time and risk of stomach cancer: A pooled analysis of data from two prospective cohort studies

Author: Fulvio Ricceri, Joseph A. Rothwell, Amanda J. Cross, Graham G. Giles, Elisabete Weiderpass, Tilman Kühn, Emily Sonestedt, Yi Yang, Rudolf Kaaks, Valeria Pala, Anna Karakatsani, Dallas R. English, Rosario Tumino, Pilar Amiano, Antonia Trichopoulou, John L. Hopper, Leila Lujan-Barroso, Allison M. Hodge, Bengt Wallner, Ruth C. Travis, María Dolores López, Anne Tjønneland, Hazel M. Mitchell, Kostas Tsilidis, Domenico Palli, Harindra Jayasekara, Elio Riboli, Antonio Agudo, Robin Room, Heiner Boeing, Eva Ardanaz, Bas Bueno-de-Mesquita, Torkjel M. Sandanger, Pietro Ferrari, Robert J. MacInnis, Susana Merino, Andrew Haydon, Eleni Peppa, Marie-Christine Boutron-Ruault, Salvatore Panico, María José Sánchez, Marc J. Gunter, Hanna Sternby, Roger L. Milne, Gianluca Severi, Ana Lucia Mayen-Chacon, Centre international de Recherche sur le Cancer (CIRC), 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, Institut Gustave Roussy (IGR), VicHealth Kræftens Bekæmpelse, DCS German Cancer Research Center, DKFZ Centre International de Recherche sur le Cancer, CIRC Wellcome Trust, WT Medical Research Council, MRC: MC‐UU_12015/1, MR/M012190/1, MR/N003284/1 British Heart Foundation, BHF Department of Health and Social Care, DH Cancer Research UK, CRUK: C570/ A16491, C8221/A19170, C864/A14136 World Cancer Research Fund, WCRF Food Standards Agency, FSA Stroke Association European Commission, EC National Health and Medical Research Council, NHMRC: 1074383, 209057, 396414, GNT1163120 Cancer Council Victoria 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 Stavros Niarchos Foundation, SNF Vetenskapsrådet, VR Consiglio Nazionale delle Ricerche, CNR Ministère des Affaires Sociales et de la Santé: GR‐IARC‐2003‐09‐12‐01 Instituto de Salud Carlos III, ISCIII 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 Ministry of Health and Social Solidarity, Greece Foundation for Alcohol Research and Education, FARE Hellenic Health Foundation, HHF, Australian National Health and Medical Research Council, Grant/Award Numbers: 1074383, 209057, 396414, GNT1163120, Cancer Council Victoria (Australia), Cancer Research UK, Grant/Award Numbers: C570/ A16491, C8221/A19170, C864/A14136, Catalan Institute of Oncology ‐ ICO (Spain), Danish Cancer Society, Deutsche Krebshilfe, the Deutsches Krebsforschungszentrum (Germany), Dutch Ministry of Public Health, Welfare and Sports, European Commission (Directorate General for Health and Consumer Affairs), Foundation for Alcohol Research and Education (Australia), French Ministry of Health, Grant/Award Number: Grant GR‐IARC‐2003‐09‐12‐01, Health Research Fund (FIS) ‐ Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, Hellenic Health Foundation (Greece), Hellenic Ministry of Health and Social Solidarity (Greece), Institut National de la Santé et de la Recherche Médicale (France), Italian Association for Research on Cancer and the National Research Council (Italy), Ligue Contre le Cancer (France), LK Research Funds, Dutch Prevention Funds, the Dutch Zorg Onderzoek Nederland, Medical Research Council (UK), Grant/Award Numbers: MC‐UU_12015/1, MR/M012190/1, MR/N003284/1, Mutuelle Générale de l'Education Nationale, National Institute for Public Health and the Environment (RIVM) (the Netherlands), Netherlands Cancer Registry, Stavros Niarchos Foundation (Greece), Stroke Association, the British Heart Foundation, the Department of Health, the Food Standards Agency and the Wellcome Trust (UK), Swedish Cancer Society, the Swedish Scientific Council and the Regional Government of Skåne (Sweden), the Federal Ministry of Education and Research (Germany), VicHealth (Australia), World Cancer Research Fund and Statistics Netherlands (the Netherlands), the Institut Gustave Roussy Funding information, We thank Carine Biessy and Bertrand Hemon for their technical contribution to EPIC data used in this work. We are also grateful to all the EPIC participants who have been part of the project, and to the many members of the study teams who enabled this research. We thank the original MCCS investigators and the diligent team, who recruited the participants and who continue working on follow‐up, for their contribution. We also express our gratitude to the many thousands of Melbourne residents who continue to participate in the study. 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 Research Funds, Dutch Prevention Funds, the Dutch Zorg Onderzoek Nederland, the World Cancer Research Fund and Statistics Netherlands (the Netherlands), the National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands, for their contribution and ongoing support to the EPIC Study, the Health Research Fund (FIS) ‐ Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology ‐ ICO (Spain), the Swedish Cancer Society, the Swedish Scientific Council and the Regional Government of Skåne (Sweden), Cancer Research UK (C864/A14136 to EPIC‐Norfolk, C570/A16491 and C8221/A19170 to EPIC‐Oxford), Medical Research Council (MR/N003284/1 and MC‐UU_12015/1 to EPIC‐Norfolk, MR/M012190/1 to EPIC‐Oxford, United Kingdom), the Stroke Association, the British Heart Foundation, the Department of Health, the Food Standards Agency and the Wellcome Trust (UK). MCCS cohort recruitment was funded by Cancer Council Victoria ( https://www.cancervic.org.au/ ) and VicHealth ( https://www.vichealth.vic.gov.au/ ). The MCCS was further supported by Australian National Health and Medical Research Council (NHMRC) ( https://www.nhmrc.gov.au/ ) grants 209057, 396414 and 1074383, and ongoing follow‐up and data management has been funded by Cancer Council Victoria since 1995. Cases and their vital status were ascertained through the Victorian Cancer Registry and the Australian Institute of Health and Welfare, including the National Death Index and the Australian Cancer Database. Harindra Jayasekara is supported by NHMRC grant GNT1163120. John L. Hopper is a NHMRC Senior Principal Research Fellow. Yi Yang is supported by a Melbourne Research Scholarship from the University of Melbourne. Robin Room's position was funded by the Foundation for Alcohol Research and Education. The sponsors had no role in the design and conduct of the study, collection, management, analysis, and interpretation of the data, preparation, review, or approval of the manuscript, and and decision to submit the manuscript for publication.
Subjects: Male, Cancer Research, Gastroenterology, 0302 clinical medicine, Prospective Studies, Stomach cancer, Prospective cohort study, stomach cancer, biology, Stomach, Incidence, Hazard ratio, Smoking, cardia cancer, Cardia cancer, Middle Aged, Lifetime alcohol intake, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, medicine.anatomical_structure, Oncology, Drinking of alcoholic beverages, 030220 oncology & carcinogenesis, Consum d'alcohol, Female, Life Sciences & Biomedicine, Cohort study, Adult, medicine.medical_specialty, Alcohol Drinking, [SDV.CAN]Life Sciences [q-bio]/Cancer, Helicobacter Infections, noncardia cancer, 03 medical and health sciences, Stomach Neoplasms, Internal medicine, medicine, Humans, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, Aged, Science & Technology, Helicobacter pylori, EPIC, lifetime alcohol intake, MCCS, business.industry, Càncer d'estómac, Kirurgi, Australia, Cancer, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Noncardia cancer, medicine.disease, biology.organism_classification, Surgery, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: Alcohol consumption is causally linked to several cancers but the evidence for stomach cancer is inconclusive. In our study, the association between long-term alcohol intake and risk of stomach cancer and its subtypes was evaluated. We performed a pooled analysis of data collected at baseline from 491 714 participants in the European Prospective Investigation into Cancer and Nutrition and the Melbourne Collaborative Cohort Study. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for incident stomach cancer in relation to lifetime alcohol intake and group-based life course intake trajectories, adjusted for potential confounders including Helicobacter pylori infection. In all, 1225 incident stomach cancers (78% noncardia) were diagnosed over 7 094 637 person-years; 984 in 382 957 study participants with lifetime alcohol intake data (5 455 507 person-years). Although lifetime alcohol intake was not associated with overall stomach cancer risk, we observed a weak positive association with noncardia cancer (HR = 1.03, 95% CI: 1.00-1.06 per 10 g/d increment), with a HR of 1.50 (95% CI: 1.08-2.09) for ≥60 g/d compared to 0.1 to 4.9 g/d. A weak inverse association with cardia cancer (HR = 0.93, 95% CI: 0.87-1.00) was also observed. HRs of 1.48 (95% CI: 1.10-1.99) for noncardia and 0.51 (95% CI: 0.26-1.03) for cardia cancer were observed for a life course trajectory characterized by heavy decreasing intake compared to light stable intake (Phomogeneity = .02). These associations did not differ appreciably by smoking or H pylori infection status. Limiting alcohol use during lifetime, particularly avoiding heavy use during early adulthood, might help prevent noncardia stomach cancer. Heterogeneous associations observed for cardia and noncardia cancers may indicate etiologic differences., National Health and Medical Research Council of Australia 1074383 209057 396414 GNT1163120, Canadian Institutes of Health Research (CIHR) Cancer Council Victoria, Cancer Research UK C570/A16491 C8221/A19170 C864/A14136, Catalan Institute of Oncology - ICO (Spain), Danish Cancer Society, Deutsche Krebshilfe, Deutsches Krebsforschungszentrum (Germany), Dutch Ministry of Public Health, Welfare and Sports, European Commission European Commission Joint Research Centre, Foundation for Alcohol Research and Education (Australia), French Ministry of Health GR-IARC-2003-09-12-01, Health Research Fund (FIS) -Instituto de Salud Carlos III (ISCIII), Junta de Andalucía, Regional Government of Asturias, Basque Government, Regional Government of Murcia, Regional Government of Navarra, Hellenic Health Foundation (Greece), Hellenic Ministry of Health and Social Solidarity (Greece), Institut National de la Sante et de la Recherche Medicale (Inserm), Consiglio Nazionale delle Ricerche (CNR), Associazione Italiana per la Ricerca sul Cancro (AIRC), Ligue Contre le Cancer (France), LK Research Funds, Dutch Prevention Funds, Netherlands Organization for Scientific Research (NWO), UK Research & Innovation (UKRI) Medical Research Council UK (MRC) MC-UU_12015/1 MR/M012190/1 MR/N003284/, Mutuelle Generale de l'Education Nationale, National Institute for Public Health and the Environment (RIVM) (the Netherlands), Netherlands Cancer Registry, Stavros Niarchos Foundation (Greece), Stroke Association (UK), British Heart Foundation, Department of Health (UK), Food Standards Agency (UK), Wellcome Trust, Swedish Cancer Society, Swedish Scientific Council (Sweden), Regional Government of Skane (Sweden), Federal Ministry of Education & Research (BMBF), VicHealth (Australia), World Cancer Research Fund and Statistics Netherlands (the Netherlands), Institut Gustave Roussy
Published: 2021

165. Cross-Cancer Genome-Wide Association Study of Endometrial Cancer and Epithelial Ovarian Cancer Identifies Genetic Risk Regions Associated with Risk of Both Cancers

Author: Ana Osorio, Fiona Bruinsma, Andrew J. Li, Janine Senz, Stacey J. Winham, Michael E. Carney, Deborah J. Thompson, Xifeng Wu, Susan J. Ramus, Alicia A. Tone, Robert P. Edwards, Chu Chen, Daniel D. Buchanan, Rüdiger Klapdor, Diether Lambrechts, Anthony N. Karnezis, Ralf Bützow, Graham G. Giles, Jolanta Kupryjanczyk, James D. Brenton, Pamela J. Thompson, Joseph L. Kelley, Hui Cai, Dylan M. Glubb, Peter Hillemanns, Veronica Wendy Setiawan, Reidun K. Kopperud, Francesmary Modugno, Rodney J. Scott, Karen H. Lu, Andreas du Bois, Weiva Sieh, Clara Bodelon, Katharina Bischof, Sarah E. Ferguson, Ignace Vergote, Todd L. Edwards, Nadeem Siddiqui, Jennifer A. Doherty, Celeste Leigh Pearce, David G. Huntsman, Håkan Olsson, Ailith Ewing, Tjoung-Won Park-Simon, Harvey A. Risch, Taymaa May, Soo Hwang Teo, Elizabeth G. Holliday, Penelope M. Webb, Lukasz Michael Szafron, Alexander Hein, Martin Köbel, Marjorie J. Riggan, Madhuri Koti, Ahmad Alsulimani, Matthias W. Beckmann, Heli Nevanlinna, Domenico Palli, Melissa C. Larson, Emily White, Ingo B. Runnebaum, Robert A. Vierkant, Elza Khusnutdinova, Jolanta Lissowska, Andrew Berchuck, Rosalind Glasspool, Drakoulis Yannoukakos, Alison M. Dunning, Rosario Tumino, Mia M. Gaudet, Alice S. Whittemore, Anna Jakubowska, Marcus Q. Bernardini, Jennifer B. Permuth, Kunle Odunsi, Aleksandra Gentry-Maharaj, Florentia Fostira, Philipp Harter, Rebecca Sutphen, Sandra Orsulic, Beata Spiewankiewicz, Susanne K. Kjaer, Jessica N. McAlpine, Valerie McGuire, Julie M. Cunningham, Jeffrey Killeen, Christine M. Friedenreich, Estrid Høgdall, George Fountzilas, Michelle A.T. Hildebrandt, Katja K.H. Aben, Tomasz Huzarski, Frédéric Amant, Zhaoming Wang, James M. Flanagan, Timothy R. Rebbeck, Joseph H. Rothstein, Clemens Liebrich, Immaculata De Vivo, Linda Titus, Anna deFazio, Jan Gawełko, Irene Konstantopoulou, Adriaan Vanderstichele, Stephen J. Chanock, Jenny Lester, Amanda B. Spurdle, Allan Jensen, Claus Høgdall, Daniela Annibali, Amalia Mattiello, Peter Kraft, Loic Le Marchand, Line Bjørge, Marina Bermisheva, Agnieszka Podgorska, John Attia, Tracy A. O'Mara, Shashikant Lele, Thomas A. Sellers, Bo Gao, Holly R. Harris, Shan Wang-Gohrke, Lingeng Lu, Louise A. Brinton, Alessandra Macciotta, Digna R. Velez Edwards, Peter A. Fasching, Marc T. Goodman, Linda S. Cook, Constance Turman, Jacek Gronwald, Liv Cecilie Vestrheim Thomsen, Matthias Dürst, Kirsten B. Moysich, Usha Menon, Dong Liang, Arif B. Ekici, Bozena Konopka, Aurelio Barricarte, Thilo Dörk, Stefanie Burghaus, Michael Jones, Loren Lipworth, Zhihua Chen, Xiaoqing Chen, Alison Brand, Iain A. McNeish, Tanja Pejovic, Florian Heitz, Beth Y. Karlan, Anthony J. Swerdlow, Anna H. Wu, Obstetrics and Gynaecology, CCA - Cancer biology and immunology, and Amsterdam Reproduction & Development (AR&D)
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, Epidemiology, Quantitative Trait Loci, Genome-wide association study, Biology, Carcinoma, Ovarian Epithelial, Genetic correlation, 03 medical and health sciences, 0302 clinical medicine, All institutes and research themes of the Radboud University Medical Center, Uterine cancer, Risk Factors, Internal medicine, medicine, Humans, Genetic association, Ovarian Neoplasms, Endometrial cancer, Cancer, medicine.disease, 3. Good health, Endometrial Neoplasms, 030104 developmental biology, 030220 oncology & carcinogenesis, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Human genome, Female, Ovarian cancer, Genome-Wide Association Study
Abstract: Background: Accumulating evidence suggests a relationship between endometrial cancer and ovarian cancer. Independent genome-wide association studies (GWAS) for endometrial cancer and ovarian cancer have identified 16 and 27 risk regions, respectively, four of which overlap between the two cancers. We aimed to identify joint endometrial and ovarian cancer risk loci by performing a meta-analysis of GWAS summary statistics from these two cancers. Methods: Using LDScore regression, we explored the genetic correlation between endometrial cancer and ovarian cancer. To identify loci associated with the risk of both cancers, we implemented a pipeline of statistical genetic analyses (i.e., inverse-variance meta-analysis, colocalization, and M-values) and performed analyses stratified by subtype. Candidate target genes were then prioritized using functional genomic data. Results: Genetic correlation analysis revealed significant genetic correlation between the two cancers (rG = 0.43, P = 2.66 × 10−5). We found seven loci associated with risk for both cancers (PBonferroni < 2.4 × 10−9). In addition, four novel subgenome-wide regions at 7p22.2, 7q22.1, 9p12, and 11q13.3 were identified (P < 5 × 10−7). Promoter-associated HiChIP chromatin loops from immortalized endometrium and ovarian cell lines and expression quantitative trait loci data highlighted candidate target genes for further investigation. Conclusions: Using cross-cancer GWAS meta-analysis, we have identified several joint endometrial and ovarian cancer risk loci and candidate target genes for future functional analysis. Impact: Our research highlights the shared genetic relationship between endometrial cancer and ovarian cancer. Further studies in larger sample sets are required to confirm our findings.
Published: 2021

166. Prospective Identification of Elevated Circulating CDCP1 in Patients Years before Onset of Lung Cancer

Author: Matthew Whitaker, Matthias B. Schulze, Barbara Bodinier, Torkjel M. Sandanger, Rosario Tumino, Carlotta Sacerdote, Mattias Johansson, Roel Vermeulen, Sonia Dagnino, Paolo Vineis, Karl Smith-Byrne, Claudia Agnoli, Dusan Petrovic, Salvatore Panico, Therese Haugdahl Nøst, Florence Guida, Marc Chadeau-Hyam, Domenico Palli, Mikael Johansson, Pekka Keski-Rahkonen, Augustin Scalbert, Cancer Research UK, Research Council of Norway, and Commission of the European Communities
Subjects: 0301 basic medicine, Oncology, Cancer Research, Lung Neoplasms, INVASION, PROTEIN, medicine.disease_cause, 0302 clinical medicine, Prospective Studies, Early Detection of Cancer, RISK, Confounding, Wnt signaling pathway, Prognosis, 3. Good health, medicine.anatomical_structure, 030220 oncology & carcinogenesis, CDCP1, Adenocarcinoma, HEALTH, medicine.symptom, Life Sciences & Biomedicine, PROJECT, medicine.medical_specialty, MODELS, Inflammation, Adenocarcinoma of Lung, Article, 03 medical and health sciences, INFLAMMATION, Antigens, CD, Antigens, Neoplasm, Internal medicine, PANTHER, medicine, Biomarkers, Tumor, Humans, COHORT, 1112 Oncology and Carcinogenesis, QUANTITATIVE PROTEOMICS, Oncology & Carcinogenesis, Lung cancer, Science & Technology, Lung, business.industry, medicine.disease, 030104 developmental biology, Case-Control Studies, Carcinogenesis, business, Cell Adhesion Molecules, Follow-Up Studies
Abstract: Increasing evidence points to a role for inflammation in lung carcinogenesis. A small number of circulating inflammatory proteins have been identified as showing elevated levels prior to lung cancer diagnosis, indicating the potential for prospective circulating protein concentration as a marker of early carcinogenesis. To identify novel markers of lung cancer risk, we measured a panel of 92 circulating inflammatory proteins in 648 prediagnostic blood samples from two prospective cohorts in Italy and Norway (women only). To preserve the comparability of results and protect against confounding factors, the main statistical analyses were conducted in women from both studies, with replication sought in men (Italian participants). Univariate and penalized regression models revealed for the first time higher blood levels of CDCP1 protein in cases that went on to develop lung cancer compared with controls, irrespective of time to diagnosis, smoking habits, and gender. This association was validated in an additional 450 samples. Associations were stronger for future cases of adenocarcinoma where CDCP1 showed better explanatory performance. Integrative analyses combining gene expression and protein levels of CDCP1 measured in the same individuals suggested a link between CDCP1 and the expression of transcripts of LRRN3 and SEM1. Enrichment analyses indicated a potential role for CDCP1 in pathways related to cell adhesion and mobility, such as the WNT/β-catenin pathway. Overall, this study identifies lung cancer–related dysregulation of CDCP1 expression years before diagnosis. Significance: Prospective proteomics analyses reveal an association between increased levels of circulating CDCP1 and lung carcinogenesis irrespective of smoking and years before diagnosis, and integrating gene expression indicates potential underlying mechanisms. See related commentary by Itzstein et al., p. 3441.
Published: 2021
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167. Transcriptome of male breast cancer matched with germline profiling reveals novel molecular subtypes with possible clinical relevance

Author: kCon Fab, Domenico Palli, Simonetta Bianchi, Veronica Zelli, Ines Zanna, Piera Rizzolo, Giuseppe Giannini, Agostino Bucalo, Virginia Valentini, Laura Ottini, Anna Coppa, Laura Cortesi, Stephen B. Fox, Valentina Silvestri, Daniele Calistri, and Maria Grazia Tibiletti
Subjects: Cancer Research, BRCA1/2, PALB2, Germline mutations, Male breast cancer, Molecular subtypes, Transcriptome profiling, male breast cancer, Biology, Germline, Article, Transcriptome, Breast cancer, Germline mutation, medicine, polycyclic compounds, skin and connective tissue diseases, RC254-282, Genetics, molecular subtypes, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Cancer, transcriptome profiling, medicine.disease, Phenotype, Oncology, germline mutations
Abstract: Simple Summary Breast cancer in men is a rare disease; however, morbidity and mortality in male breast cancer (MBC) patients is a serious concern. The identification of specific molecular features in MBC is essential for developing more appropriate and targeted therapeutic strategies for MBC patients. In this study, by transcriptome analysis of 63 MBCs characterized for germline mutations in the most relevant BC susceptibility genes, mainly BRCA1/2, we highlighted possible differences in the molecular pathways underlying MBC pathogenesis in relation to germline mutation status. Furthermore, we identified two distinct subgroups of MBCs of clinical relevance, which are characterized by different biological features and prognosis. Overall, our results showed that transcriptome profiling by RNA sequencing is a valuable approach to dissect the molecular heterogeneity of MBC and suggest that the transcriptome matched with germline profiling may lead to the identification of MBC subtypes with possible relevance in the clinical setting, which is a primary step to improve the clinical management of MBC patients. Abstract Male breast cancer (MBC) is a rare and understudied disease compared with female BC. About 15% of MBCs are associated with germline mutation in BC susceptibility genes, mainly BRCA1/2 and PALB2. Hereditary MBCs are likely to represent a subgroup of tumors with a peculiar phenotype. Here, we performed a whole transcriptome analysis of MBCs characterized for germline mutations in the most relevant BC susceptibility genes in order to identify molecular subtypes with clinical relevance. A series of 63 MBCs, including 16 BRCA2, 6 BRCA1, 2 PALB2, 1 RAD50, and 1 RAD51D germline-mutated cases, was analyzed by RNA-sequencing. Differential expression and hierarchical clustering analyses were performed. Module signatures associated with central biological processes involved in breast cancer pathogenesis were also examined. Different transcriptome profiles for genes mainly involved in the cell cycle, DNA damage, and DNA repair pathways emerged between MBCs with and without germline mutations. Unsupervised clustering analysis revealed two distinct subgroups, one of which was characterized by a higher expression of immune response genes, high scores of gene-expression signatures suggestive of aggressive behavior, and worse overall survival. Our results suggest that transcriptome matched with germline profiling may be a valuable approach for the identification and characterization of MBC subtypes with possible relevance in the clinical setting.
Published: 2021

168. DNA methylation-based biomarkers of aging were slowed down in a two-year diet and physical activity intervention trial: the DAMA study

Author: Ilaria Ermini, Domenico Palli, Melania Assedi, Benedetta Bendinelli, D. Ambrogetti, Laura Ottini, Giovanni Fiorito, Giovanna Masala, Calogero Saieva, Virginia Valentini, Saverio Caini, and Piera Rizzolo
Subjects: Male, Oncology, Aging, medicine.medical_specialty, Time Factors, media_common.quotation_subject, physical activity, postmenopausal women, primary prevention trial, Biology, law.invention, Biomarkers of aging, Randomized controlled trial, law, Internal medicine, medicine, Humans, Epigenetics, Exercise, Pathological, dietary habits, media_common, Original Paper, DNA methylation, epigenetic clock, epigenetic mutation load, Longevity, dNaM, Cell Biology, Original Papers, Biomarker (medicine), Female, Diet Therapy
Abstract: Several biomarkers of healthy aging have been proposed in recent years, including the epigenetic clocks, based on DNA methylation (DNAm) measures, which are getting increasingly accurate in predicting the individual biological age. The recently developed “next‐generation clock” DNAmGrimAge outperforms “first‐generation clocks” in predicting longevity and the onset of many age‐related pathological conditions and diseases. Additionally, the total number of stochastic epigenetic mutations (SEMs), also known as the epigenetic mutation load (EML), has been proposed as a complementary DNAm‐based biomarker of healthy aging. A fundamental biological property of epigenetic, and in particular DNAm modifications, is the potential reversibility of the effect, raising questions about the possible slowdown of epigenetic aging by modifying one's lifestyle. Here, we investigated whether improved dietary habits and increased physical activity have favorable effects on aging biomarkers in healthy postmenopausal women. The study sample consists of 219 women from the “Diet, Physical Activity, and Mammography” (DAMA) study: a 24‐month randomized factorial intervention trial with DNAm measured twice, at baseline and the end of the trial. Women who participated in the dietary intervention had a significant slowing of the DNAmGrimAge clock, whereas increasing physical activity led to a significant reduction of SEMs in crucial cancer‐related pathways. Our study provides strong evidence of a causal association between lifestyle modification and slowing down of DNAm aging biomarkers. This randomized trial elucidates the causal relationship between lifestyle and healthy aging‐related epigenetic mechanisms., In a 24‐month randomized factorial intervention trial, dietary and physical activity interventions slowed down DNA methylation‐based biomarkers of aging.
Published: 2021

169. Family History and Gastric Cancer Risk: A Pooled Investigation in the Stomach Cancer Pooling (STOP) Project Consortium

Author: Areti Lagiou, María Rubín-García, Nuria Aragonés, Akihisa Hidaka, Lina Mu, Matteo Rota, Weimin Ye, Vicente Martín, Yolanda Benavente, Carlo La Vecchia, Monica Ferraroni, Nuno Lunet, Mohammadreza Pakseresht, Domenico Palli, Dmitry Maximovich, Farhad Pourfarzi, Zuo-Feng Zhang, Shoichiro Tsugane, Amelie Plymoth, Manuela García-de-la-Hera, Roberta Pastorino, Gerson Shigueaki Hamada, Reza Malekzadeh, Pagona Lagiou, Jesús Vioque, Gemma Castaño-Vinyals, Facundo Vitelli-Storelli, Samantha Morais, Claudio Pelucchi, Guo-Pei Yu, David Zaridze, Stefania Boccia, Eva Negri, Rossella Bonzi, Instituto de Saúde Pública da Universidade do Porto, Vitelli-Storelli F., Rubin-Garcia M., Pelucchi C., Benavente Y., Bonzi R., Rota M., Palli D., Ferraroni M., Lunet N., Morais S., Ye W., Plymoth A., Malekzadeh R., Tsugane S., Hidaka A., Aragones N., Castano-Vinyals G., Zaridze D.G., Maximovich D., Vioque J., Garcia-de-la-Hera M., Zhang Z.-F., Hamada G.S., Pakseresht M., Pourfarzi F., Mu L., Boccia S., Pastorino R., Yu G.-P., Lagiou A., Lagiou P., Negri E., Vecchia C.L., and Martin V.
Subjects: Cancer Research, medicine.medical_specialty, Stomach cancer, Pooling, Oncology and Carcinogenesis, Article, Stomach--Cancer, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Epidemiology, medicine, Family history, Gastric cancer, International consortium, Meta-analyses, Socioeconomic status, Settore MED/42 - IGIENE GENERALE E APPLICATA, RC254-282, Cancer, family history, Medical records, business.industry, Prevention, gastric cancer, Càncer d'estómac, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Odds ratio, medicine.disease, Confidence interval, Oncology, international consortium, meta-analyses, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Digestive Diseases, business, Històries clíniques
Abstract: Although there is a clear relationship between family history (FH) and the risk of gastric cancer (GC), quantification is still needed in relation to different histological types and anatomical sites, and in strata of covariates. The objective was to analyze the risk of GC according to first-degree FH in a uniquely large epidemiological consortium of GC. This investigation includes 5946 cases and 12,776 controls from 17 studies of the Stomach Cancer Pooling (StoP) Project consortium. Summary odds ratios (OR) and the corresponding 95% confidence intervals (CIs) were calculated by pooling study-specific ORs using fixed-effect model meta-analysis techniques. Stratified analyses were carried out by sex, age, tumor location and histological type, smoking habit, socioeconomic status, alcohol intake and fruit consumption. The pooled OR for GC was 1.84 (95% CI: 1.64–2.04, I2 = 6.1%, P heterogeneity = 0.383) in subjects with vs. those without first-degree relatives with GC. No significant differences were observed among subgroups of sex, age, geographic area or study period. Associations tended to be stronger for non-cardia (OR = 1.82, 95% CI: 1.59–2.05 for subjects with FH) than for cardia GC (OR = 1.38, 95% CI: 0.98–1.77), and for the intestinal (OR = 1.92, 95% CI: 1.62–2.23) than for the diffuse histotype (OR = 1.62, 95% CI: 1.28–1.96). This analysis confirms the effect of FH on the risk of GC, reporting an approximately doubled risk, and provides further quantification of the risk of GC according to the subsite and histotype. Considering these findings, accounting for the presence of FH to carry out correct prevention and diagnosis measures is of the utmost importance.
Published: 2021

170. Inflammatory marker changes in a 24-month dietary and physical activity randomised intervention trial in postmenopausal women

Author: Ilaria Ermini, Melania Assedi, C Della Bella, Giovanna Masala, Calogero Saieva, Simona Tapinassi, Maria Castaldo, Daniela Occhini, Mario Milco D'Elios, Benedetta Bendinelli, Domenico Palli, and Saverio Caini
Subjects: 0301 basic medicine, medicine.medical_specialty, Disease prevention, Science, medicine.medical_treatment, Psychological intervention, Inflammation, Article, Cancer prevention, law.invention, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Aged, Biomarkers, C-Reactive Protein, Cytokines, Female, Follow-Up Studies, Humans, Middle Aged, Postmenopause, Exercise, medicine, Multidisciplinary, business.industry, Health care, Cancer, diet, postmenopausal, cytokines, medicine.disease, 030104 developmental biology, 030220 oncology & carcinogenesis, Medicine, Tumor necrosis factor alpha, Hormone therapy, medicine.symptom, business
Abstract: Chronic low-grade inflammation plays a role in the pathogenesis of several chronic diseases including cancer. Physical activity (PA) and diet have been supposed to modulate inflammatory markers. We evaluated the effects of a 24-month dietary and/or PA intervention on plasma levels of pro-inflammatory cytokines, a secondary analysis in the DAMA factorial trial. The 234 study participants (healthy postmenopausal women with high breast density, 50–69 years, non smokers, no hormone therapy) were randomised to four arms: (1) isocaloric dietary intervention mainly based on plant-foods; (2) moderate-intensity PA intervention with at least 1 h/week of supervised strenuous activity; (3) both interventions; (4) general recommendations on healthy dietary and PA patterns. Interleukins (IL)-1α, -1β, -6, tumor necrosis factor-α and C-reactive protein were measured at baseline and at the end of the intervention. Intention-to-treat-analyses were carried out using Tobit regression. Although all cytokines tended to increase over time, after 24 months women in the PA intervention (arms 2 + 3) showed lower levels of IL-1α (exp(β) = 0.66; p = 0.04) and IL-6 (exp(β) = 0.70; p = 0.01) in comparison with women in the control group (arms 1 + 4). No effects of the dietary intervention emerged. In healthy postmenopausal women with high breast density a moderate-intensity PA appears to slow the age-related increase of pro-inflammatory cytokines.
Published: 2020

171. Author response: Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight

Author: Zahra Mohammadi, Abdul Basit, Helena I. S. Nogueira, Soile E. Puhakka, Hongsheng Bi, Ari Voutilainen, Davood Khalili, Bin Zhou, Dermot O'Reilly, Natascia Rinaldo, Paulo A. Lotufo, Bahareh Kheiri, Thein Thein Htay, Simona Giampaoli, Goodarz Danaei, M. Fernanda Lima-Costa, Simona Bo, Peter Schnohr, Jerzy Chudek, Francesco Panza, Ling Yang, Katia Vergetti Bloch, Vincenzo Capuano, Holly E. Syddall, Dong Zhao, Indah Suci Widyahening, Maria Lorenza Muiesan, Leng Huat Foo, Mohsen Azimi-Nezhad, Merete Osler, Laura Torres-Collado, Manu Raj, Adroaldo Cesar Araujo Gaya, Susi Kriemler, Ali Akbar Shayesteh, Aneta Grajda, Anette Varbo, Kazem Mohammad, Leila Beltrami Moreira, Shu Ti Chiou, Iuliia A Rusakova, Jyh Eiin Wong, Torben Jørgensen, Lela Sturua, Lubica Ticha, Hamid Hakimi, Hazzaa M. Al-Hazzaa, Yanina Zócalo, Freda Pitakaka, Savvas C. Savva, Rajeev Gupta, Jennifer Servais, Marie Kunešová, Johanna M. Geleijnse, Elysée Claude Bika Lele, Yannis Manios, Jorge Escobedo-de la Peña, Yufang Bi, Chinh Nguyen Huu, Sibel Gogen, Viviane Cunha Cardoso, Kristine H. Allin, Ana Azevedo, Line Tang Møllehave, Vincent Jr DeGennaro, Novie O. Younger-Coleman, Gretchen A Stevens, Dickman Gareta, Holger Theobald, Anja Schienkiewitz, Bekbolat Zholdin, Janice Luisa Lukrafka, Adela Chirita-Emandi, Ulla Roggenbuck, Kenisha Russell Jonsson, Robespierre Ribeiro, Gabriele Eiben, Eero Kajantie, Sounnia Mediene Benchekor, Fariborz Mansour-Ghanaei, Mary Simon, Prakash C. Gupta, Mohammad Esmaeel Motlagh, Emanuela Gualdi-Russo, María Elena Díaz-Sánchez, Pilar Guallar-Castillón, Bee Koon Poh, Cristina Padez, Azaliia M Tuliakova, Sarah P. Garnett, William R. Tebar, Yingfeng Zheng, Suhad Bahijri, Christina Mavrogianni, Mihaela Vladulescu, Jan A. Staessen, Paula Duarte de Oliveira, Rui Ornelas, Michael Sjöström, Charles Agyemang, Slawomir Koziel, Shohreh Naderimagham, Jari Jokelainen, Stephen T. 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Otero, Jamila Abubakar Garba, Antonio Pedro Graça, Sumit Bharadwaj, Shiqi Zhen, Xiu-Hua Guo, Prashant Mathur, Raphael Mendes Ritti-Dias, Kouamelan Doua, Esteban Carmuega, Majid Shirani, Przemyslaw Slusarczyk, Petra Rust, Visnja Djordjic, Farahnaz Joukar, Johanna Gunnlaugsdottir, Leila Houti, Nayu Ikeda, Imperia Brajkovich, Amirabbas Momenan, Erik J. Timmermans, Marcin Rutkowski, Biruta Velika, Joana Araújo, Jostein Steene-Johannessen, Christa L. Lilly, Per Tynelius, Michael Tornaritis, Anne Juolevi, Fatima Zahra Laamiri, Carl Lachat, Kai-Uwe Saum, Espen Bjertness, Ana P. Ortiz, Joel G. R. Roy, Himanshu K. Chaturvedi, Michelle Holdsworth, Niels Wedderkopp, Johan Van der Heyden, Mukharram M. Bikbov, Hsien-Ho Lin, Eva Corpeleijn, Harshpal Singh Sachdev, Mohammad Reza Mirjalili, Maria del Cristo Rodriguez-Perez, Michala Lustigová, Tuyen D Le, Teresa Norat, Hana Zamrazilová, Garry Brian, Tien Yin Wong, Rosa Haghshenas, Clive Osmond, Diego Giulliano Destro Christofaro, Mahmood Moosazadeh, Vilma Irazola, Olli T. Raitakari, Marco Aurélio Peres, Terho Lehtimäki, Shuohua Chen, Dimitrios Papandreou, Robert J. Adams, Sigmund A. Anderssen, Peter T. Katzmarzyk, Luisa M Macieira, Félicité Tchibindat, Lital Keinan Boker, Toshiharu Ninomiya, Morten Sodemann, Jytte Halkjær, Zbigniew Kułaga, Sophie Visvikis-Siest, Farshad Farzadfar, N Capkova, Zumin Shi, Maria Turley, Zbigniew Gaciong, Giovanni Veronesi, Martin McKee, Veikko Salomaa, Gilad Twig, Elisabetta L. Romeo, Peter Kristensen, Grazyna Jasienska, Victor Guillermo Sequera, Mario V. Capanzana, Con Burns, Emanuela Pettenuzzo, Ming-Dong Wang, Jonathan Giovannelli, Stela McLachlan, Ellis Owusu-Dabo, Stefania Toselli, Maria Teresa Anselmo Olinto, Senthil K Vasan, Sara Schramm, Xenophon Theodoridis, Moyses Szklo, Ramfis Nieto-Martínez, Viswanathan Mohan, Guillermo Frontera, Rahul Malhotra, Thomas Ferrao, Dongfeng Gu, Tomas Vega, Hynek Pikhart, Päivi Mäki, Heba Fouad, Vilnis Dzerve, Christina Howitt, Seyed Mohammad Hashemi-Shahri, Jenny M. Kindblom, Marjolijn C. E. Bragt, G. K. Mini, Qian Wang, Liufu Cui, Andrzej Galbarczyk, Sylvain Sebert, Vilmundur Gudnason, Loreto Santa Marina, Kairat Davletov, Afshin Ostovar, Niloofar Peykari, Nicholas J. Wareham, Wilma M. Hopman, Karl-Heinz Jöckel, Jussi Kauhanen, Breige A. McNulty, Alina Kerimkulova, Youcef Laid, Claes Ohlsson, Stefan Kiechl, Alicia Matijasevich, Boban Mugoša, Srinivasan Kannan, Jyrki K. Virtanen, Mohan Deepa, Mangesh S. Pednekar, Shahla AlDhukair, Cynthia M. Pérez, Vera Lanska, Tint Swe Latt, Dominique Hange, João Luiz Bastos, Eliza Markidou Ioannidou, Leticia Hernandez Cadena, Maya Tanrygulyyeva, Reza Malekzadeh, Dimitrios Poulimeneas, Pedro Ordunez, Thomas Waldhör, Ioannis Pagkalos, Carlo M. Barbagallo, Abla M. Sibai, Peter Vollenweider, Asher Fawwad, Emily Sonestedt, Elena Pahomova, Santosh K. Bhargava, Patrick Kolsteren, Aya Mostafa, Fangfang Chen, Flavio Nervi, Imre Janszky, Arvind Pandey, Renata Cifkova, Alexandre C. Pereira, Alejandro Diaz, Alireza Ansari-Moghaddam, Rachakulla Hari Kumar, Jaakko Mursu, Luis A. Moreno, Glen Gironella, Jelena Kos, Tilema Cama, Haakon E. Meyer, Jun Ma, Raphael E. Arku, Ziad Abdeen, Rusidah Selamat, Dianna J. Magliano, Jitendra Jonnagaddala, Konstantinos Gkiouras, Paul Korrovits, Paola Nardone, Paolo Vineis, Kotsedi D Monyeki, Khuong Quynh Long, Alberto Barceló, Camilla T. Damsgaard, Constance Schultsz, Frank J Rühli, Santiago F. Gomez, Tara Coppinger, Muhammad Islam, Pierre Traissac, Eleonora d'Orsi, Irfan Nuhoglu, Rui Providência, Bernard Maire, Leandra Abarca-Gómez, Sinead Brophy, Daniela Pierannunzio, Cristina Taddei, Wen-Harn Pan, Gregor Starc, Abdullah Alkandari, Saeed Dastgiri, Lien Braeckevelt, Gustavo Velasquez-Melendez, Sudhir Kowlessur, Bagher Larijani, Cynthia Robitaille, Mohamed M. Ali, Steiner Krokstad, Noor Ani Ahmad, Anar Dushpanova, Agustinus Soemantri, Susana Sans, Ionela Pascanu, Gwenaëlle Le Coroller, Inger Ariansen, Abhijit Sen, Sergej M. Ostojic, Silvana Donoso, Felix K. Assah, Juan A Rivera, Peter H. Whincup, Oana-Florentina Gheorghe-Fronea, Hanan F. Abdul Rahim, Yadlapalli S. Kusuma, Michael Knoflach, Moein Yoosefi, Cassiano Ricardo Rech, Paul Ferdinand M. Reganit, Tomi-Pekka Tuomainen, Francesco Gianfagna, Stefania Maggi, Mohammad Hossein Somi, Behrooz Hamzeh, Bethlehem D. Solomon, Herman Borghs, Zhanna Kalmatayeva, Heidi Klakk, Akram Pourshams, Naomi S. Levitt, Miquel Porta, Vesna Jureša, Alexander D. Deev, Son Thai Pham, Paula Margozzini, Silvia Bel-Serrat, Dora Romaguera, Monira Alarouj, Winsome R. Parnell, Marloes Cardol, David Faeh, Antonio Bernabe-Ortiz, Giota Touloumi, Maryam Kavousi, Sanja Musić Milanović, Jalila El Ati, Sauli Herrala, Liang Xu, Sirkka Keinänen-Kiukaanniemi, Ian Hambleton, Stefan Savin, Andre Pascal Kengne, R. Krishna Kumar, Kurt Widhalm, Marco M Ferrario, Parisa Amiri, Yi Song, Jianfeng Wu, Jeannette Klimont, Jean Ferrières, Farhad Zamani, Shina Avi, Luis Paulo Gomes Mascarenhas, Aluísio J D Barros, Reecha Sofat, Koen Van Herck, Hoang Van Minh, Enrique Gutiérrez-González, Martine Vrijheid, Susana Cararo Confortin, Antonis Zampelas, Bogdan Wojtyniak, Ausra Petrauskiene, Juha Auvinen, Maryam Sharafkhah, Emanuel Zitt, Majid Ezzati, Young-Ho Khang, Ellina Rakhimova, Magdalena Klimek, Luís Lopes, Erkin M. Mirrakhimov, Maria Lc Iurilli, Günay Can, Mark Woodward, Esther Lopez-Garcia, Mauro Virgílio Gomes de Barros, Ahmed A. Madar, Rainford J. Wilks, Shoaib Afzal, Melanie J. Cowan, Gareth Stratton, Eduardo Salazar Martinez, Sameer Narake, Norie Sawada, Li Juan Wu, Adrian Richter, Licia Iacoviello, Hanno Ulmer, Deepak Amarapurkar, Mohsen Ibrahim, Hamed Pouraram, Massimo Salvetti, Hung-Kwan So, Yonghua Hu, Lars Ängquist, Thi Tuyet-Hanh Tran, Charles Lunogelo, Sabina Zambon, Angelika Schaffrath Rosario, Lauren Lissner, Kamarul Imran Musa, Deepa Weerasekera, Bihungum Bista, Takafumi Ishida, Ekaterina Chikova-Iscener, Mirjam M. Heinen, Tazeen H. Jafar, Semánová Csilla, Raija Korpelainen, Edward W. Gregg, Laura Gutierrez, Victor M. Herrera, Aristides M. Machado-Rodrigues, Fatemeh Malekzadeh, Shouling Wu, Jennifer L. Baker, Clicerio González-Villalpando, Irene G. M. van Valkengoed, Anna Fijałkowska, Meghnath Dhimal, Murat Topbaş, George Moschonis, Robert Eggertsen, Quang Ngoc Nguyen, Janette Walton, Elnaz Faramarzi, Nasheeta Peer, Radka Taxová Braunerová, Harald Geiger, Morteza Shamshirgaran, Lela Shengelia, María Ángeles Dal Re Saavedra, Khem Bahadur Karki, Timothy J. Key, Maria G. Grammatikopoulou, Susana Vale, Bernhard O. Boehm, Songhomitra Panda-Jonas, Iveta Pudule, Elisabete Ramos, Lacramioara Aurelia Brinduse, Paul H. Lee, Terence W O'Neill, Javad Aghazadeh-Attari, Margus Punab, Bojan Jelaković, Eliza Cinteza, Ha Tp Do, and Alison J. Hayes
Subjects: education.field_of_study, business.industry, Population, Distribution (economics), medicine.disease, Obesity, Geography, medicine, Underweight, medicine.symptom, education, business, Body mass index, Demography
Published: 2020

172. Time Course and Determinants of Individual Motivation among Women Enrolled in a Diet and Physical Activity Primary Prevention Trial

Author: Donatella Zagni, Domenico Palli, Giovanna Masala, Maria Castaldo, Daniela Occhini, Benedetta Bendinelli, Elisa Grechi, Melania Assedi, Ilaria Ermini, and Saverio Caini
Subjects: Gerontology, Time Factors, Health, Toxicology and Mutagenesis, primary prevention, Physical activity, lcsh:Medicine, physical activity levels, Article, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Primary prevention, Intervention (counseling), Vegetables, Medicine, Humans, 030212 general & internal medicine, dietary habits, randomized intervention trial, Exercise, Aged, Consumption (economics), Motivation, business.industry, lcsh:R, Public Health, Environmental and Occupational Health, Middle Aged, Diet, Health promotion, Red Meat Consumption, 030220 oncology & carcinogenesis, Time course, Female, business
Abstract: We studied the determinants of motivation among post-menopausal women enrolled in a two-year diet and physical activity primary prevention randomized trial. Participants were requested to grade the importance attached to changing their lifestyle, their confidence about being able to implement the change, and their willingness to be involved in studies focusing on lifestyle. We used multi-adjusted regression to investigate the association between individual characteristics, study arm, and individual motivation at study entry and end. Participants (n = 234) were highly motivated both at entry and throughout the study. Women with pre-existing healthier eating habits and lifestyles (e.g., high consumption of fruit and vegetables, low red meat consumption, and physically active) were more motivated at entry and over the course of the study. Women assigned to any intervention arm were more motivated than those in the control arm. These findings may help enhance adherence to recommendations and improve effectiveness of community-based health promotion campaigns.
Published: 2020

173. Blood Transcriptome Response to Environmental Metal Exposure Reveals Potential Biological Processes Related to Alzheimer's Disease

Author: Thomas Lundh, Theo M. de Kok, Soterios A. Kyrtopoulos, Domenico Palli, Anders Johansson, Jos C. S. Kleinjans, Julian Krauskopf, Ingvar A. Bergdahl, Toxicogenomics, RS: GROW - R1 - Prevention, RS: FSE MaCSBio, RS: FPN MaCSBio, RS: FHML MaCSBio, and RS: MHeNs - R3 - Neuroscience
Subjects: Male, Apolipoprotein E, Microarray, PROTEIN, Disease, Alzheimer&apos, Transcriptome, transcriptomics, 0302 clinical medicine, LEAD-EXPOSURE, 030212 general & internal medicine, BRAIN, Biological Phenomena, Original Research, education.field_of_study, lcsh:Public aspects of medicine, 030503 health policy & services, Neurodegenerative Diseases, MOUSE MODEL, Alzheimer's disease, Female, HEALTH, Public Health, AMYLOID-BETA DEPOSITION, 0305 other medical science, microarray, APOE, EXPRESSION, Population, metals, Biology, MECHANISMS, s disease, CADMIUM, Arbetsmedicin och miljömedicin, 03 medical and health sciences, Downregulation and upregulation, Alzheimer Disease, Humans, education, Carcinogen, Public Health, Environmental and Occupational Health, lcsh:RA1-1270, Environmental Exposure, Occupational Health and Environmental Health, Immunology, gene expression, Neutrophil degranulation, TAU
Abstract: Alzheimer's disease (AD) is a neurodegenerative disease which is manifested by a progressive and irreversible decline of cognition, memory loss, a shortened attention span, and changes in personality. Aging and genetic pre-dispositions, particularly the presence of a specific form of apolipoprotein E (APOE), are main risk factors of sporadic AD; however, a large body of evidence has shown that multiple environmental factors, including exposure to toxic metals, increase the risk for late onset AD. Lead (Pb) and cadmium (Cd) are ubiquitous toxic metals with a wide range of applications resulting in global distribution in the environment and exposure of all living organisms on earth. In addition to being classified as carcinogenic (Cd) and possibly carcinogenic (Pb) to humans by the International Agency for Research on Cancer, both compounds disrupt metal homeostasis and can cause toxic responses at the cellular and organismal levels. Pb toxicity targets the central nervous system and evidence for that has emerged also for Cd. Recent epidemiological studies show that both metals possibly are etiological factors of multiple neurodegenerative diseases, including Alzheimer's disease (AD). To further explore the association between metal exposure and AD risk we applied whole transcriptome gene expression analysis in peripheral blood leukocytes (PBLs) from 632 subjects of the general population, taken from the EnviroGenomarkers project. We used linear mixed effect models to associate metal exposure to gene expression after adjustment for gender, age, BMI, smoking, and alcohol consumption. For Pb exposure only few associations were identified, including a downregulation of the human eukaryotic translation initiation factor 5 (eIF5). In contrast, Cd exposure, particularly in males, revealed a much stronger transcriptomic response, featuring multiple pathways related to pathomolecular mechanisms of AD, such as endocytosis, neutrophil degranulation, and Interleukin-7 signaling. A gender stratified analysis revealed that the Cd responses were male-specific and included a downregulation of the APOE gene in men. This exploratory study revealed novel hypothetical findings which might contribute to the understanding of the neurotoxic effects of chronic Pb and Cd exposure and possibly improve our knowledge on the molecular mechanisms linking metal exposure to AD risk.
Published: 2020

174. Common susceptibility loci for male breast cancer

Author: Giovanna Masala, Susan L. Neuhausen, Montserrat Garcia Closas, Vasilios Georgoulias, Paul D.P. Pharoah, Katarzyna Tomczyk, Henrik Flyger, Håkan Olsson, D. Timothy Bishop, Alison M. Dunning, Eitan Friedman, Matthew Pugh, Michael Jones, Johanna Mattson, Sarah Maguire, Richard S. Houlston, Paul A. James, Douglas F. Easton, Valentina Silvestri, Srdjan Novaković, Rosie Cooke, Maartje J. Hooning, Eleni Perraki, Manuela Gago-Dominguez, Domenico Palli, Laura Ottini, Nick Orr, Kyle Thompson, Heli Nevanlinna, Yael Laitman, Antoinette Hollestelle, Stig E. Bojesen, Timothy Winter, Alison H. Trainer, Ines Zanna, Mateja Krajc, Linda Steele, Jose E. Castelao, Emmanouil Saloustros, Olivia Fletcher, Ingrid Hedenfalk, Alan Ashworth, Anthony J. Swerdlow, Medical Oncology, HUS Gynecology and Obstetrics, Biosciences, Department of Obstetrics and Gynecology, HUS Comprehensive Cancer Center, Department of Oncology, University of Helsinki, and Helsinki University Hospital Area
Subjects: Male, Oncology, Cancer Research, Linkage disequilibrium, IDENTIFIES 2, Genome-wide association study, PHENOTYPE, Linkage Disequilibrium, 0302 clinical medicine, MULTIPLE, Odds Ratio, skin and connective tissue diseases, 0303 health sciences, Articles, OVARIAN, Receptors, Estrogen, 030220 oncology & carcinogenesis, Male breast cancer, Female, male breast cancer, SNPs, GWAS, cancer risk, AcademicSubjects/MED00010, EXPRESSION, medicine.medical_specialty, 3122 Cancers, Quantitative Trait Loci, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Breast Neoplasms, Male, 03 medical and health sciences, Breast cancer, SDG 3 - Good Health and Well-being, Internal medicine, Confidence Intervals, medicine, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, FUNCTIONAL VARIANTS, Genotyping, METAANALYSIS, RISK LOCUS, 030304 developmental biology, Case-control study, Odds ratio, medicine.disease, Case-Control Studies, Linear Models, Genome-Wide Association Study
Abstract: BackgroundThe aetiology of male breast cancer (MBC) is poorly understood. In particular, the extent to which the genetic basis of MBC differs from female breast cancer (FBC) is unknown. A previous genome-wide association study (GWAS) of MBC identified two predisposition loci for the disease, both of which were also associated with risk of FBC.MethodsWe performed genome-wide single nucleotide polymorphism (SNP) genotyping of European ancestry MBC case subjects and controls, in three stages. Associations between directly genotyped and imputed SNPs with MBC were assessed using fixed-effects meta-analysis of 1,380 cases and 3,620 controls. Replication genotyping of 810 cases and 1,026 controls was used to validate variants with P-values < 1 x 10-06. Genetic correlation with FBC was evaluated using LD score regression, by comprehensively examining the associations of published FBC risk loci with risk of MBC and by assessing associations between a FBC polygenic risk score (PRS) and MBC. All statistical tests were two-sided.ResultsThe GWAS identified three novel MBC susceptibility loci that attained genome-wide significance (P < 5 x 10-08). Genetic correlation analysis revealed a strong shared genetic basis with estrogen-receptor (ER) positive FBC. Males in the top quintile of genetic risk had a four-fold increased risk of breast cancer relative to those in the bottom quintile (odds ratio = 3.86, 95% confidence interval = 3.07 to 4.87, P = 2.08 x 10-30).ConclusionsThese findings advance our understanding of the genetic basis of MBC, providing support for an overlapping genetic aetiology with FBC and identifying a four-fold high risk group of susceptible men.
Published: 2020

175. Stochastic Epigenetic Mutations Are Associated with Risk of Breast Cancer, Lung Cancer, and Mature B-cell Neoplasms

Author: Graham G. Giles, Salvatore Panico, Rosario Tumino, Giovanni Fiorito, Torkjel M. Sandanger, Sonia Tarallo, Vittorio Krogh, Melissa C. Southey, Domenico Palli, Pierre Antoine Dugué, Gianluca Severi, Amedeo Gagliardi, Daniel F. Schmidt, Paolo Vineis, Silvia Polidoro, Therese Haugdahl Nøst, Nicole Wong Doo, Dallas R. English, Roger L. Milne, Carlotta Sacerdote, Laura Baglietto, Allison M. Hodge, Daniel D. Buchanan, Luigia Pace, Barbara Pardini, Eiliv Lund, Enes Makalic, Alessio Naccarati, and John L. Hopper
Subjects: 0301 basic medicine, Oncology, Male, medicine.medical_specialty, Lung Neoplasms, Lymphoma, Epidemiology, Breast Neoplasms, Epigenesis, Genetic, Female, Humans, Lymphoma, Large B-Cell, Diffuse, Middle Aged, Mutation, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Genetic, Internal medicine, medicine, Large B-Cell, Neoplasm, Epigenetics, Lung cancer, business.industry, VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762, Cancer, medicine.disease, Diffuse, 3. Good health, VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762, 030104 developmental biology, CpG site, 030220 oncology & carcinogenesis, DNA methylation, Biomarker (medicine), business, Epigenesis
Abstract: Background: Age-related epigenetic dysregulations are associated with several diseases, including cancer. The number of stochastic epigenetic mutations (SEM) has been suggested as a biomarker of life-course accumulation of exposure-related DNA damage; however, the predictive role of SEMs in cancer has seldom been investigated. Methods: A SEM, at a given CpG site, was defined as an extreme outlier of DNA methylation value distribution across individuals. We investigated the association of the total number of SEMs with the risk of eight cancers in 4,497 case–control pairs nested in three prospective cohorts. Furthermore, we investigated whether SEMs were randomly distributed across the genome or enriched in functional genomic regions. Results: In the three-study meta-analysis, the estimated ORs per one-unit increase in log(SEM) from logistic regression models adjusted for age and cancer risk factors were 1.25; 95% confidence interval (CI), 1.11–1.41 for breast cancer, and 1.23; 95% CI, 1.07–1.42 for lung cancer. In the Melbourne Collaborative Cohort Study, the OR for mature B-cell neoplasm was 1.46; 95% CI, 1.25–1.71. Enrichment analyses indicated that SEMs frequently occur in silenced genomic regions and in transcription factor binding sites regulated by EZH2 and SUZ12 (P < 0.0001 and P = 0.0005, respectively): two components of the polycomb repressive complex 2 (PCR2). Finally, we showed that PCR2-specific SEMs are generally more stable over time compared with SEMs occurring in the whole genome. Conclusions: The number of SEMs is associated with a higher risk of different cancers in prediagnostic blood samples. Impact: We identified a candidate biomarker for cancer early detection, and we described a carcinogenesis mechanism involving PCR2 complex proteins worthy of further investigations.
Published: 2020

176. Cross-cancer genome-wide association study of endometrial cancer and epithelial ovarian cancer identifies genetic risk regions associated with risk of both cancers

Author: Clara Bodelon, Anna H. Wu, V. Wendy Setiawan, Jenny Lester, Adriaan Vanderstichele, Daniela Annibali, Michael E. Carney, Jennifer A. Doherty, Shashikant Lele, Jacek Gronwald, Matthias W. Beckmann, George Fountzilas, Christine M. Friedenreich, Heli Nevanlinna, Immaculata De Vivo, Jolanta Lissowska, Soo Hwang Teo, Ahmad Alsulimani, Daniel D. Buchanan, Rosalind Glasspool, Domenico Palli, Madhuri Koti, Katja K.H. Aben, Tanja Pejovic, Linda S. Cook, Line Bjørge, Mia M. Gaudet, Anna Jakubowska, Tomasz Huzarski, Florian Heitz, Beth Y. Karlan, Andreas du Bois, Linda J. Titus, Joseph L. Kelley, Andrew Berchuck, Aleksandra Gentry-Maharaj, Florentia Fostira, Weiva Sieh, Anthony J. Swerdlow, Celeste Leigh Pearce, Constance Turman, Zhaoming Wang, Ignace Vergote, Dylan M. Glubb, Peter Hillemanns, Chu Chen, Tjoung-Won Park-Simon, Andrew J. Li, Susanne K. Kjaer, Jan Gawełko, Stephen J. Chanock, Tracy A. O'Mara, Elizabeth G. Holliday, Jessica N. McAlpine, Ailith Ewing, Amalia Mattiello, Pamela J. Thompson, Xifeng Wu, Alicia A. Tone, Ana Osorio, Fiona Bruinsma, Digna R. Velez Edwards, Janine Senz, Francesmary Modugno, Michael Jones, Sandra Orsulic, Xiaoqing Chen, Todd L. Edwards, Aurelio Barricarte, Hui Cai, Loren Lipworth, David G. Huntsman, Zhihua Chen, Alison M. Dunning, Julie M. Cunningham, Rosario Tumino, Melissa C. Larson, Ralf Bützow, Alison Brand, Allan Jensen, Marina Bermisheva, Reidun K. Kopperud, Beata Spiewankiewicz, Timothy R. Rebbeck, Bozena Konopka, Matthias Dürst, Thomas A. Sellers, Penelope M. Webb, Claus Høgdall, Anthony N. Karnezis, Håkan Olsson, Liv Cecilie Vestrheim Thomsen, Rodney J. Scott, Iain A. McNeish, Arif B. Ekici, Valerie McGuire, Lukasz Szafron, Harvey A. Risch, Bo Gao, Louise A. Brinton, Alessandra Macciotta, Anna deFazio, Rüdiger Klapdor, Graham G. Giles, Usha Menon, Marc T. Goodman, Robert P. Edwards, Robert A. Vierkant, Dong Liang, Shan Wang-Gohrke, Lingeng Lu, Kirsten B. Moysich, Holly R. Harris, Deborah J. Thompson, Jennifer B. Permuth, Alexander Hein, Thilo Dörk, Elza Khusnutdinova, Stefanie Burghaus, Irene Konstantopoulou, Stacey J. Winham, Susan J. Ramus, Agnieszka Podgorska, Rebecca Sutphen, Michelle A.T. Hildebrandt, Jolanta Kupryjanczyk, Ingo B. Runnebaum, James D. Brenton, Karen H. Lu, Katharina Bischof, Nadeem Siddiqui, Drakoulis Yannoukakos, Estrid Høgdall, John Attia, Clemens Liebrich, Loic Le Marchand, Emily White, Amanda B. Spurdle, Peter Kraft, Alice S. Whittemore, Kunle Odunsi, Sarah E. Ferguson, Taymaa May, Marjorie J. Riggan, Philipp Harter, Jeffrey Killeen, James M. Flanagan, Frédéric Amant, Marcus Q. Bernardini, Joseph H. Rothstein, Martin Köbel, Peter A. Fasching, and Diether Lambrechts
Subjects: Oncology, 0303 health sciences, medicine.medical_specialty, business.industry, Endometrial cancer, Genome-wide association study, medicine.disease, Genetic correlation, 3. Good health, 03 medical and health sciences, Serous fluid, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, Epidemiology, medicine, Epithelial ovarian cancer, business, Clear cell, 030304 developmental biology, Genetic association
Abstract: Accumulating evidence suggests a relationship between endometrial cancer and epithelial ovarian cancer. For example, endometrial cancer and epithelial ovarian cancer share epidemiological risk factors and molecular features observed across histotypes are held in common (e.g. serous, endometrioid and clear cell). Independent genome-wide association studies (GWAS) for endometrial cancer and epithelial ovarian cancer have identified 16 and 27 risk regions, respectively, four of which overlap between the two cancers. Using GWAS summary statistics, we explored the shared genetic etiology between endometrial cancer and epithelial ovarian cancer. Genetic correlation analysis using LD Score regression revealed significant genetic correlation between the two cancers (rG = 0.43, P = 2.66 × 10−5). To identify loci associated with the risk of both cancers, we implemented a pipeline of statistical genetic analyses (i.e. inverse-variance meta-analysis, co-localization, and M-values), and performed analyses by stratified by subtype. We found seven loci associated with risk for both cancers (PBonferroni < 2.4 × 10−9). In addition, four novel regions at 7p22.2, 7q22.1, 9p12 and 11q13.3 were identified at a sub-genome wide threshold (P < 5 × 10−7). Integration with promoter-associated HiChIP chromatin loops from immortalized endometrium and epithelial ovarian cell lines, and expression quantitative trait loci (eQTL) data highlighted candidate target genes for further investigation.
Published: 2020
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177. Association of genomic domains in BRCA1 and BRCA2 with prostate cancer risk and aggressiveness

Author: Henriette Roed Nielsen, Judith Balmaña, Anne-Marie Gerdes, Ellen Honisch, Melissa C. Southey, Ramunas Janavicius, Finn Cilius Nielsen, Douglas F. Easton, Linda Steele, Ava Kwong, Sung Won Kim, Bjarni A. Agnarsson, Piera Rizzolo, Angela R. Solano, Mads Thomassen, Johannes Lemke, Grazia Artioli, Heli Nevanlinna, Johanna I. Kiiski, Frans B. L. Hogervorst, Jong Won Lee, Diana Eccles, Mark H. Greene, Marc Tischkowitz, David E. Goldgar, Angela R. Bradbury, Javier Benitez, Marie Navratilova, Dominique Stoppa-Lyonnet, Arjen R. Mensenkamp, Alfons Meindl, Zisun Kim, Nadine Tung, Agnes Jager, Matthew L. Freedman, Ana Osorio, Norbert Arnold, Doris Steinemann, Inge Søkilde Pedersen, Patricia Llovet, Rob B. van der Luijt, Vivek L Patel, Munaza Ahmed, Lidia Moserle, Irene Konstantopoulou, Jackie Cook, Jacques Simard, Joan Brunet, Johanna Rantala, Kai-ren Ong, Carole Brewer, Joe Dennis, Sook-Yee Yoon, Hanne Meijers-Heijboer, Roberta Villa, Katie Snape, Louise Izatt, Ana Peixoto, Susan M. Domchek, Nina Ditsch, D. Gareth Evans, Tara M. Friebel, Sue K. Park, Katherine L. Nathanson, Lenka Foretova, Miguel Angel Pujana, Edith Olah, Hélène Schuster, Raymonda Varon-Mateeva, Silvia Tognazzo, Payal D. Shah, Oskar T. Johannsson, Hans Ehrencrona, Paul Gesta, Ian G. Campbell, Drakoulis Yannoukakos, Mirjam Larsen, Anthony V. D'Amico, Liene Nikitina-Zake, Davide Bondavalli, Valérie Bonadona, Paul A. James, Alan Donaldson, Antonis C. Antoniou, Bernd Auber, Andrew K. Godwin, Denise Molina Gomes, Jihyoun Lee, Laurence Faivre, Almuth Caliebe, Pilar Garre, Siddhartha Yadav, Julika Borde, Pedro Pérez-Segura, Birgitte Bertelsen, Paolo Peterlongo, Michael T. Parsons, John L. Hopper, Bruno Buecher, Goska Leslie, Shan Wang-Gohrke, Amanda B. Spurdle, T.M. Mooij, Juliane Ramser, kConFab Investigators, Lídia Feliubadaló, Susanne E. Boonen, Bernard Peissel, Anna von Wachenfeldt, Timothy R. Rebbeck, Christi J. van Asperen, Víctor Lorca, Estela Carrasco, Elisa Alducci, Ulrike Faust, Karin Kast, Gord Glendon, Saundra S. Buys, Fergus J. Couch, Mariarosaria Calvello, Istvan Bodrogi, Kathryn J. Ruddy, Philipp Wagner, Fabienne Lesueur, Evan L. Busch, Hebon Investigators, Laura Cortesi, Christian F. Singer, Ute Hamann, Giuseppe Damante, Stefania Tommasi, Esther M. John, Jacopo Azzollini, Cristina Zanzottera, Angelica M. Gutierrez-Barrera, Emmanuelle Mouret-Fourme, Claire Saule, Rosa B. Barkardottir, Kristin K. Zorn, Kerstin Rhiem, Uffe Birk Jensen, Mark Pomerantz, Yuan Chun Ding, Alison H. Trainer, Marco Montagna, Vijai Joseph, Domenico Palli, Kwang-Pil Ko, Angel M. Cronin, Susan L. Neuhausen, Dieter Niederacher, Laura Ottini, Angela Toss, Rita K. Schmutzler, Muriel Belotti, Jeffrey N. Weitzel, Caroline M. Seynaeve, Ileana Carnevali, Adalgeir Arason, Rosalind A. Eeles, Annie T W Chu, Florentia Fostira, Greet Wieme, Brita Arver, Charlotte Kvist Lautrup, Christoph Engel, Marion Gauthier-Villars, Daniel Barrowdale, Caroline Maria Rossing, Kenneth Offit, Kathleen Claes, Olufunmilayo I. Olopade, Penny Soucy, Alicia Barroso, Manuel R. Teixeira, Wendy K. Chung, Gero Kramer, Tsun Leung Chan, Agostina Stradella, Debra Frost, Noura Mebirouk, Liselotte P. van Hest, Esther Darder, Valentina Silvestri, Annabeth Høgh Petersen, Lesley McGuffog, Andrea Gehrig, Mary Porteous, Matti A. Rookus, Lizet E. van der Kolk, Siranoush Manoukian, Lone Sunde, Conxi Lázaro, Maria A. Caligo, Priyanka Sharma, Anne-Bine Skytte, Claus-Eric Ott, Christian Sutter, Paolo Radice, Veronica Medici, Georgia Chenevix-Trench, Vanesa García-Barberán, Kristiina Aittomäki, Amanda E. Toland, Anna Marie Mulligan, Véronique Mari, Bernd Dworniczak, Lynn Martin, Lara Della Puppa, Phuong L. Mai, George Fountzilas, Yen Y. Tan, Simona Agata, Torben A Kruse, Trinidad Caldés, Rosemarie Davidson, Daniel R. Barnes, Thomas Dyrso Jensen, Åke Borg, Mark E. Robson, Jennifer T. Loud, Vivian Y. Shin, Irene López-Perolio, Leigha Senter, Irene L. Andrulis, Rosa Scarpitta, Angela F. Brady, Annika Lindblom, Diana Torres, Lotte Nylandsted Krogh, Barbara Wappenschmidt, Muhammad Rashid, Jeroen Vierstraete, Mary B. Daly, Annelie Liljegren, Frederieke H. van der Baan, Eunyoung Kang, Alessandra Viel, Santiago Cabezas-Camarero, Eric Hahnen, Laura Matricardi, Marinus J. Blok, Edmond S. K. Ma, Maria Grazia Tibiletti, Catarina Santos, Julian Adlard, Soo Hwang Teo, Giuseppe Giannini, Jan Hauke, Peter J. Hulick, Miguel de la Hoya, Clare Miller, Bernardo Bonanni, Bent Ejlertsen, Lajos Géczi, Liliana Varesco, Orland Diez, N Herold, Christine Lasset, Adrià López-Fernández, Min Hyuk Lee, Medicum, Kristiina Aittomäki / Principal Investigator, HUSLAB, Department of Medical and Clinical Genetics, University of Helsinki, INDIVIDRUG - Individualized Drug Therapy, HUS Gynecology and Obstetrics, Clinicum, Department of Obstetrics and Gynecology, RS: GROW - R4 - Reproductive and Perinatal Medicine, MUMC+: DA KG Lab Centraal Lab (9), Medical Oncology, Academic Medical Center, ARD - Amsterdam Reproduction and Development, Leslie, Goska [0000-0001-5756-6222], Adlard, Julian [0000-0002-1693-0435], Arnold, Norbert [0000-0003-4523-8808], Auber, Bernd [0000-0003-1880-291X], Azzollini, Jacopo [0000-0002-9364-9778], Barnes, Daniel R [0000-0002-3781-7570], Brunet, Joan [0000-0003-1945-3512], Caligo, Maria A [0000-0003-0589-1829], Campbell, Ian G [0000-0002-7773-4155], Claes, Kathleen BM [0000-0003-0841-7372], Darder, Esther [0000-0002-7764-1397], Dennis, Joe [0000-0003-4591-1214], Dworniczak, Bernd [0000-0003-4981-7903], Eeles, Rosalind A [0000-0002-3698-6241], Ehrencrona, Hans [0000-0002-5589-3622], Ejlertsen, Bent [0000-0001-8761-714X], Evans, D Gareth [0000-0002-8482-5784], Garre, Pilar [0000-0001-8285-4138], Greene, Mark H [0000-0003-1852-9239], Hulick, Peter J [0000-0001-8397-4078], Jager, Agnes [0000-0002-7713-1450], James, Paul [0000-0002-4361-4657], John, Esther M [0000-0003-3259-8003], Joseph, Vijai [0000-0002-7933-151X], Kim, Sung-Won [0000-0002-1413-2800], Kim, Zisun [0000-0002-1413-2800], Konstantopoulou, Irene [0000-0002-0470-0309], Lesueur, Fabienne [0000-0001-7404-4549], Matricardi, Laura [0000-0002-0241-1810], Gomes, Denise Molina [0000-0002-2836-9008], Nevanlinna, Heli [0000-0002-0916-2976], Olopade, Olufunmilayo I [0000-0002-9936-1599], Palli, Domenico [0000-0002-5558-2437], Park, Sue K [0000-0001-5002-9707], Parsons, Michael T [0000-0003-3242-8477], Peterlongo, Paolo [0000-0001-6951-6855], Petersen, Annabeth Høgh [0000-0002-4503-6942], Pujana, Miguel Angel [0000-0003-3222-4044], Ruddy, Kathryn J [0000-0001-6298-332X], Scarpitta, Rosa [0000-0001-7590-3827], Shah, Payal D [0000-0001-5874-3390], Silvestri, Valentina [0000-0003-0712-9379], Southey, Melissa C [0000-0002-6313-9005], Spurdle, Amanda B [0000-0003-1337-7897], Stoppa-Lyonnet, Dominique [0000-0002-5438-8309], Sunde, Lone [0000-0002-8479-165X], Teixeira, Manuel R [0000-0002-4896-5982], Teo, Soo Hwang [0000-0002-0444-590X], Tommasi, Stefania [0000-0002-2157-2978], Toss, Angela [0000-0002-1854-6701], van der Luijt, Rob B [0000-0002-0018-1089], Vierstraete, Jeroen [0000-0001-7909-6620], Wieme, Greet [0000-0003-2718-5300], Yadav, Siddhartha [0000-0003-4630-9903], Antoniou, Antonis C [0000-0001-9223-3116], Apollo - University of Cambridge Repository, Human genetics, and CCA - Cancer biology and immunology
Subjects: Male, 0301 basic medicine, Oncology, Cancer Research, endocrine system diseases, PHENOTYPE, INCREASE, Prostate cancer, 0302 clinical medicine, Risk Factors, Young adult, skin and connective tissue diseases, Aged, 80 and over, Prostate cancer risk, Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17], MESSENGER-RNA DECAY, BRCA1 Protein, Genomics, GERMLINE MUTATIONS, Middle Aged, Prognosis, OVARIAN, CARRIERS, 3. Good health, 030220 oncology & carcinogenesis, Adult, Heterozygote, medicine.medical_specialty, Adolescent, Tumor suppressor gene, Urology, Association (object-oriented programming), 3122 Cancers, MEDLINE, Article, Young Adult, 03 medical and health sciences, Breast cancer, Germline mutation, SDG 3 - Good Health and Well-being, Internal medicine, BRCA1, BRCA2, Prostate Cancer, Pathogenic sequence variant location, Risk estimation, Journal Article, Genetic predisposition, medicine, Humans, BREAST-CANCER, Genetic Predisposition to Disease, Risk factor, Genetic Association Studies, Aged, BRCA2 Protein, IDENTIFICATION, business.industry, Prostatic Neoplasms, medicine.disease, GENE, Confidence interval, APC, 030104 developmental biology, Mutation, 3111 Biomedicine, business
Abstract: Pathogenic sequence variants (PSV) in BRCA1 or BRCA2 (BRCA1/2) are associated with increased risk and severity of prostate cancer. We evaluated whether PSVs in BRCA1/2 were associated with risk of overall prostate cancer or high grade (Gleason 8+) prostate cancer using an international sample of 65 BRCA1 and 171 BRCA2 male PSV carriers with prostate cancer, and 3,388 BRCA1 and 2,880 BRCA2 male PSV carriers without prostate cancer. PSVs in the 3′ region of BRCA2 (c.7914+) were significantly associated with elevated risk of prostate cancer compared with reference bin c.1001-c.7913 [HR = 1.78; 95% confidence interval (CI), 1.25–2.52; P = 0.001], as well as elevated risk of Gleason 8+ prostate cancer (HR = 3.11; 95% CI, 1.63–5.95; P = 0.001). c.756-c.1000 was also associated with elevated prostate cancer risk (HR = 2.83; 95% CI, 1.71–4.68; P = 0.00004) and elevated risk of Gleason 8+ prostate cancer (HR = 4.95; 95% CI, 2.12–11.54; P = 0.0002). No genotype–phenotype associations were detected for PSVs in BRCA1. These results demonstrate that specific BRCA2 PSVs may be associated with elevated risk of developing aggressive prostate cancer. Significance: Aggressive prostate cancer risk in BRCA2 mutation carriers may vary according to the specific BRCA2 mutation inherited by the at-risk individual.
Published: 2020

178. Citrus intake and risk of skin cancer in the European Prospective Investigation into Cancer and Nutrition cohort (EPIC)

Author: Christina Lasheras, Kim Overvad, Verena Katzke, Domenico Palli, Marina Kvaskoff, Saverio Caini, Pilar Amiano, Emily Sonestedt, Sara Grioni, Aurora Perez-Cornago, Anja Olsen, Augustin Scalbert, Anne Tjønneland, Christina C. Dahm, Elisabete Weiderpass, Guri Skeie, Tilman Kühn, Eleni Peppa, Matthias B. Schulze, Marie Al-Rahmoun, Marit B. Veierød, Carlotta Sacerdote, Reza Ghiasvand, Paula Jakszyn, Francesca Mancini, Antonia Trichopoulou, Marie-Christine Boutron-Ruault, Miguel Rodríguez-Barranco, Salvatore Panico, Iris Cervenka, Fulvio Ricceri, Ana Ezponda, Rosario Tumino, Edoardo Botteri, Gianluca Severi, Carlo La Vecchia, Yahya Mahamat-Saleh, and Sandra Colorado-Yohar
Subjects: Oncology, Adult, Keratinocytes, Male, medicine.medical_specialty, Citrus, Skin Neoplasms, Epidemiology, Nutritional Status, 030204 cardiovascular system & hematology, Risk Assessment, VDP::Medical disciplines: 700::Health sciences: 800::Nutrition: 811, VDP::Medisinske Fag: 700::Helsefag: 800::Ernæring: 811, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Basal cell carcinoma, 030212 general & internal medicine, Prospective cohort study, Melanoma, Aged, business.industry, VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762, Hazard ratio, Middle Aged, Keratinocyte cancers, medicine.disease, European Prospective Investigation into Cancer and Nutrition, VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762, Europe, Cohort studies, Cutaneous melanoma, Female, Cohort, Skin cancer, business, Cohort study
Abstract: Citrus intake has been suggested to increase the risk of skin cancer. Although this relation is highly plausible biologically, epidemiologic evidence is lacking. We aimed to examine the potential association between citrus intake and skin cancer risk. EPIC is an ongoing multi-center prospective cohort initiated in 1992 and involving ~ 520,000 participants who have been followed-up in 23 centers from 10 European countries. Dietary data were collected at baseline using validated country-specific dietary questionnaires. We used Cox proportional hazards regression models to compute hazard ratios (HR) and 95% confidence intervals (CI). During a mean follow-up of 13.7 years, 8448 skin cancer cases were identified among 270,112 participants. We observed a positive linear dose–response relationship between total citrus intake and skin cancer risk (HR = 1.10, 95% CI 1.03–1.18 in the highest vs. lowest quartile; Ptrend = 0.001), particularly with basal cell carcinoma (BCC) (HR = 1.11, 95% CI 1.02–1.20, Ptrend = 0.007) and squamous cell carcinoma (SCC) (HR = 1.23, 95% CI 1.04–1.47, Ptrend = 0.01). Citrus fruit intake was positively associated with skin cancer risk (HR = 1.08, 95% CI 1.01–1.16, Ptrend = 0.01), particularly with melanoma (HR = 1.23, 95% CI 1.02–1.48; Ptrend = 0.01), although with no heterogeneity across skin cancer types (Phomogeneity = 0.21). Citrus juice was positively associated with skin cancer risk (Ptrend = 0.004), particularly with BCC (Ptrend = 0.008) and SCC (Ptrend = 0.004), but not with melanoma (Phomogeneity = 0.02). Our study suggests moderate positive linear dose–response relationships between citrus intake and skin cancer risk. Studies with available biomarker data and the ability to examine sun exposure behaviors are warranted to clarify these associations and examine the phototoxicity mechanisms of furocoumarin-rich foods.
Published: 2020

179. Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length

Author: Joris Deelen, Antonia Trichopoulou, Sara Hägg, Kim Overvad, Elisabete Weiderpass, Iryna O. Fedko, Rudolf Kaaks, Nicola D. Kerrison, Kirsi H. Pietiläinen, Ida Surakka, Veikko Salomaa, Svetlana Stoma, Jaakko Kaprio, Alessandra Allione, Cornelia M. van Duijn, Nicholas G. Martin, Veryan Codd, Olle Melander, Nilesh J. Samani, Josine E. Verhoeven, Anne Tjønneland, Natalia Pervjakova, Domenico Palli, Adam S. Butterworth, Nicholas J. Wareham, María Dolores Chirlaque, P. Eline Slagboom, Massimo Mangino, Pascal P. Arp, Christopher P. Nelson, Brenda W.J.H. Penninx, Jessica L. Buxton, Pietro Ferrari, Tao Jiang, Iiris Hovatta, Taylor K. Loe, N. Charlotte Onland-Moret, Salvatore Panico, Peter Jones, Heiner Boeing, Timothy J. Key, Luca A. Lotta, Miguel Rodríguez-Barranco, Diana van Heemst, Chen Li, Robert A. Scott, Sarah E. Medland, Giuseppe Matullo, Alexessander Couto Alves, Rosario Tumino, Jouke-Jan Hottenga, Ken K. Ong, Vittorio Krogh, Gonneke Willemsen, Andres Metspalu, Eva Albrecht, Elina Sillanpää, Johan G. Eriksson, Najaf Amin, Dale R. Nyholt, Reedik Mägi, Eros Lazzerini Denchi, Peter M. Nilsson, André G. Uitterlinden, Antonio Agudo, Yuri Milaneschi, Ashley van der Spek, Alessia Russo, Linda Broer, Federico Canzian, Marian Beekman, Grant W. Montgomery, Sophie C Warner, Guy Fagherazzi, Markus Perola, Alexandra I. F. Blakemore, Marjo-Riitta Järvelin, Robert Karlsson, Tim D. Spector, Paul W. Franks, H. Eka D. Suchiman, Claudia Langenberg, Liher Imaz, Nancy L. Pedersen, Scott D. Gordon, Stephen E. Hamby, J. Ramón Quirós, Yvonne T. van der Schouw, Concha Moreno, Christian Gieger, Pekka Jousilahti, Dorret I. Boomsma, Marc J. Gunter, Benjamin Miraglio, Gianluca Severi, John Danesh, UNIVERSITY OF OULU, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Mental Health, APH - Personalized Medicine, APH - Methodology, Sociology and Social Gerontology, Li, Chen [0000-0002-6423-6325], Ong, Kenneth [0000-0003-4689-7530], Butterworth, Adam [0000-0002-6915-9015], Danesh, John [0000-0003-1158-6791], Wareham, Nicholas [0000-0003-1422-2993], Langenberg, Claudia [0000-0002-5017-7344], Apollo - University of Cambridge Repository, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, APH - Digital Health, Institute for Molecular Medicine Finland, University of Helsinki, Research Programs Unit, CAMM - Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, HUS Abdominal Center, Department of Medicine, Endokrinologian yksikkö, Clinicum, Diabetes and Obesity Research Program, Department of General Practice and Primary Health Care, HUS Helsinki and Uusimaa Hospital District, Department of Psychology and Logopedics, Genetics, SLEEPWELL Research Program, Department of Public Health, Mind and Matter, Internal Medicine, and Epidemiology
Subjects: Netherlands Twin Register (NTR), Limfomes, LOCI, Genome-wide association study, Disease, VARIANTS, DISEASE, 0302 clinical medicine, Leukocytes, telomere length, GWAS, Genetics(clinical), Càncer, Mendelian randomisation, Thyroid cancer, Genetics (clinical), 11 Medical and Health Sciences, Cancer, Genetics, Genetics & Heredity, RISK, 0303 health sciences, Telòmer, age-related disease, biological aging, Humans, Nucleotides, Genome-Wide Association Study, Telomere, meta-analyysi, genomiikka, Genomics, CANCER, 3. Good health, 030220 oncology & carcinogenesis, MENDELIAN RANDOMIZATION, Medical genetics, Biomarker (medicine), HEART, Lymphomas, Life Sciences & Biomedicine, Medical Genetics, medicine.medical_specialty, GENES, DATABASE, Age-related Disease, Biological Aging, Mendelian Randomisation, Telomere Length, Biology, Article, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Mendelian randomization, medicine, Journal Article, 030304 developmental biology, Medicinsk genetik, Science & Technology, 06 Biological Sciences, medicine.disease, Genòmica, ikääntyminen, 1182 Biochemistry, cell and molecular biology, telomeerit, biological
Abstract: Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1, PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.
Published: 2020

180. Consumption of Fish and Long-chain n-3 Polyunsaturated Fatty Acids Is Associated With Reduced Risk of Colorectal Cancer in a Large European Cohort

Author: Magritt Brustad, Veronika Fedirko, Marc J. Gunter, Anja Olsen, Antonia Trichopoulou, Geneviève Nicolas, Anna Karakatsani, Veronique Chajes, Gianluca Severi, Elom K. Aglago, Eva Ardanaz, Aurora Perez-Cornago, Kim Overvad, Cristina Lasheras, Salvatore Panico, Verena Katzke, Bas Bueno-de-Mesquita, José María Huerta, Neil Murphy, Christina C. Dahm, Maria Wennberg, Teresa Norat, Bodil Ohlsson, Elisabete Weiderpass, Antonio Agudo, Heather Ward, Anne Tjønneland, Valeria Pala, Tilman Kühn, Bethany Van Guelpen, Guri Skeie, Rosario Tumino, María José Sánchez, A. M. May, Corinne Casagrande, Jeroen W.G. Derksen, Marie-Christine Boutron-Ruault, Elio Riboli, Agnès Fournier, Sophie Hellstrand, Inge Huybrechts, Georgia Martimianaki, Alessio Naccarati, Tobias Pischon, Amanda J. Cross, Pilar Amiano, Domenico Palli, 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), RD06/0020 6236 Kræftens Bekæmpelse, DCS German Cancer Research Center, DKFZ Centre International de Recherche sur le Cancer, CIRC Wellcome Trust, WT: C570/A16491, C8221/A19170, MR/M012190/1 National Research Council, NRC Medical Research Council, MRC British Heart Foundation, BHF Cancer Research UK, CRUK World Cancer Research Fund, WCRF: WCRF 2013/1002 Food Standards Agency, FSA Stroke Association 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 Stavros Niarchos Foundation, SNF Instituto de Salud Carlos III, ISCIII Associazione Italiana per la Ricerca sul Cancro, AIRC Deutsche Krebshilfe Associazione Iblea per la Ricerca Epidemiologica, AIRE Institut Gustave-Roussy Mutuelle Générale de l'Education Nationale, MGEN Ministry of Health and Social Solidarity, Greece Fondation Gustave Roussy Hellenic Health Foundation, HHF, Funding Supported by a grant from the World Cancer Research Fund ( WCRF ) to Marc Gunter (grant number: WCRF 2013/1002 ). 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 , and Institut National de la Santé et de la Recherche Médicale ( INSERM ) (France), German Cancer Aid , German Cancer Research Center ( DKFZ ), and Federal Ministry of Education and Research ( BMBF ) (Germany), Hellenic Health Foundation , Stavros Niarchos Foundation , and the Hellenic Ministry of Health and Social Solidarity (Greece), Italian Association for Research on Cancer ( AIRC ), National Research Council , and Associazione Iblea per la Ricerca Epidemiologica (AIRE-ONLUS) Ragusa, Associazione Volontari Italiani Sangu ( AVIS ) Ragusa, Sicilian Government (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), Nordic Center of Excellence Programme on Food, Nutrition and Health (Norway), Health Research Fund (FIS), Regional Governments of Andalucía , Asturias, Basque Country, Murcia (No. 6236) and Navarra, and the Centro de Investigación Biomédica en Red en Epidemiología y Salud Pública and Instituto de Salud Carlos II ( 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 , Stroke Association , British Heart Foundation , Department of Health , Food Standards Agency , the Wellcome Trust (UK), Cancer Research UK ( 14136 to EPIC-Norfolk, C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council ( 1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom)., Funding Supported by a grant from the World Cancer Research Fund (WCRF) to Marc Gunter (grant number: WCRF 2013/1002). 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 G?n?rale de l'Education Nationale, and Institut National de la Sant? et de la Recherche M?dicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), and Federal Ministry of Education and Research (BMBF) (Germany), Hellenic Health Foundation, Stavros Niarchos Foundation, and the Hellenic Ministry of Health and Social Solidarity (Greece), Italian Association for Research on Cancer (AIRC), National Research Council, and Associazione Iblea per la Ricerca Epidemiologica (AIRE-ONLUS) Ragusa, Associazione Volontari Italiani Sangu (AVIS) Ragusa, Sicilian Government (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), Health Research Fund (FIS), Regional Governments of Andaluc?a, Asturias, Basque Country, Murcia (No. 6236) and Navarra, and the Centro de Investigaci?n Biom?dica en Red en Epidemiolog?a y Salud P?blica and Instituto de Salud Carlos II (ISCIII RETIC) (RD06/0020) (Spain), Swedish Cancer Society, Swedish Scientific Council, and Regional Government of Sk?ne and V?sterbotten (Sweden), Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, the Wellcome Trust (UK), 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: Colorectal cancer, [SDV]Life Sciences [q-bio], Àcids grassos insaturats, Physiology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Càncer colorectal, Fatty Acids, Omega-3, Medicine, Animals, Humans, Prospective Studies, 2. Zero hunger, chemistry.chemical_classification, Unsaturated fatty acids, Epidemiologic, Gastroenterology & Hepatology, Hepatology, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, business.industry, Gastroenterology, Fishes, 1103 Clinical Sciences, Odds ratio, medicine.disease, Eicosapentaenoic acid, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Diet, chemistry, Seafood, Docosahexaenoic acid, 030220 oncology & carcinogenesis, Omega 3, Cohort, Colonic Neoplasms, Tumorigenesis, 030211 gastroenterology & hepatology, Docosapentaenoic acid, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business, Polyunsaturated fatty acid
Abstract: Background & Aims There is an unclear association between intake of fish and long-chain n-3 polyunsaturated fatty acids (n-3 LC-PUFAs) and colorectal cancer (CRC). We examined the association between fish consumption, dietary and circulating levels of n-3 LC-PUFAs, and ratio of n-6:n-3 LC-PUFA with CRC using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods Dietary intake of fish (total, fatty/oily, lean/white) and n-3 LC-PUFA were estimated by food frequency questionnaires given to 521,324 participants in the EPIC study; among these, 6291 individuals developed CRC (median follow up, 14.9 years). Levels of phospholipid LC-PUFA were measured by gas chromatography in plasma samples from a sub-group of 461 CRC cases and 461 matched individuals without CRC (controls). Multivariable Cox proportional hazards and conditional logistic regression models were used to calculate hazard ratios (HRs) and odds ratios (ORs), respectively, with 95% CIs. Results Total intake of fish (HR for quintile 5 vs 1, 0.88; 95% CI, 0.80–0.96; Ptrend = .005), fatty fish (HR for quintile 5 vs 1, 0.90; 95% CI, 0.82–0.98; Ptrend = .009), and lean fish (HR for quintile 5 vs 1, 0.91; 95% CI, 0.83–1.00; Ptrend = .016) were inversely associated with CRC incidence. Intake of total n-3 LC-PUFA (HR for quintile 5 vs 1, 0.86; 95% CI, 0.78–0.95; Ptrend = .010) was also associated with reduced risk of CRC, whereas dietary ratio of n-6:n-3 LC-PUFA was associated with increased risk of CRC (HR for quintile 5 vs 1, 1.31; 95% CI, 1.18–1.45; Ptrend < .001). Plasma levels of phospholipid n-3 LC-PUFA was not associated with overall CRC risk, but an inverse trend was observed for proximal compared with distal colon cancer (Pheterogeneity = .026). Conclusions In an analysis of dietary patterns of participants in the EPIC study, we found regular consumption of fish, at recommended levels, to be associated with a lower risk of CRC, possibly through exposure to n-3 LC-PUFA. Levels of n-3 LC-PUFA in plasma were not associated with CRC risk, but there may be differences in risk at different regions of the colon.
Published: 2020

181. Cumulative Burden of Colorectal Cancer–Associated Genetic Variants Is More Strongly Associated With Early-Onset vs Late-Onset Cancer

Author: Ludmila Vodickova, Douglas A. Corley, Phyllis J. Goodman, Albert de la Chapelle, Cornelia M. Ulrich, Gianluca Severi, Alexi N. Archambault, Douglas F. Easton, Stephanie L. Schmit, Victor Moreno, Tilman Kühn, Fredrick R. Schumacher, D. Timothy Bishop, Sonja I. Berndt, Domenico Palli, Fränzel J.B. Van Duijnhoven, Jose E. Castelao, Mingyang Song, Anna H. Wu, Wen Yi Huang, Sergi Castellví-Bel, Ulrike Peters, Stephen J. Chanock, Sanford D. Markowitz, Heather Hampel, Jenny Chang-Claude, Andrea Gsur, Stephanie J. Weinstein, Edith J. M. Feskens, Christopher A. Haiman, Mengmeng Du, Melissa C. Southey, John A. Baron, Bethany Van Guelpen, Kala Visvanathan, Loic Le Marchand, Victor Muñoz-Garzón, Ellen Kampman, Andrea N. Burnett-Hartman, Polly A. Newcomb, Paul D.P. Pharoah, Erin M. Siegel, Mark A. Jenkins, Gad Rennert, Tabitha A. Harrison, Neil Murphy, Antonia Trichopoulou, Sébastien Küry, Elizabeth L. Barry, Stephan Buch, Jochen Hampe, Minta Thomas, Vicente Martín, Michael O. Woods, Demetrius Albanes, Jeroen R. Huyghe, Robert S. Sandler, Li Hsu, Emily White, John L. Hopper, Rachel Pearlman, Peter T. Campbell, Peter S. Liang, Yin Cao, Amanda J. Cross, Graham G. Giles, Robert E. Schoen, Robert J. MacInnis, David Duggan, Michael Hoffmeister, Corinne E. Joshu, Christopher K. Edlund, Elizabeth A. Platz, Liesel M. FitzGerald, Anne Zeleniuch-Jacquotte, Hermann Brenner, Heinz-Josef Lenz, Lori C. Sakoda, Jane C. Figueiredo, Yu Ru Su, Stephen B. Gruber, Satu Männistö, Stephen N. Thibodeau, Christoph Mancao, Dallas R. English, Thomas J. Hudson, Li Li, John D. Potter, Andreana N. Holowatyj, David V. Conti, Temitope O. Keku, Sophia Harlid, Eric J. Jacobs, Jihyoun Jeon, Amit Joshi, Clemens Schafmayer, Pavel Vodicka, Leticia Moreira, María Dolores Chirlaque, Yi Lin, David J. Hunter, Michelle Cotterchio, Martha L. Slattery, Alicja Wolk, Roger L. Milne, Marc J. Gunter, Susanna C. Larsson, Annika Lindblom, Graham Casey, Christopher I. Li, Aung Ko Win, Ban Younghusband, Stefanie Brezina, Stephanie A. Bien, Lynne R. Wilkens, Daniela Seminara, Daniel D. Buchanan, Stéphane Bézieau, Manuela Gago-Dominguez, Patrick S. Parfrey, Hedy S. Rennert, Ann G. Zauber, Elisabeth F.P. Peterse, Faye Elliott, Catherine M. Tangen, Andrew T. Chan, Richard B. Hayes, Steven Gallinger, Amanda E. Toland, Noralane M. Lindor, María José Sánchez, Korbinian Weigl, Kenneth Offit, Iris Lansdorp-Vogelaar, Pharoah, Paul [0000-0001-8494-732X], Easton, Douglas [0000-0003-2444-3247], Apollo - University of Cambridge Repository, and Public Health
Subjects: 0301 basic medicine, Oncology, Male, COLONOSCOPY, Genotyping Techniques, Nutrition and Disease, DNA Mutational Analysis, Datasets as Topic, Penetrance, HEREDITARY, Cohort Studies, 0302 clinical medicine, Mutation Rate, Risk Factors, Voeding en Ziekte, Family history, Age of Onset, Medical History Taking, education.field_of_study, Colon Cancer, HERITABILITY, Gastroenterology, Middle Aged, Lynch syndrome, Cohort, 030211 gastroenterology & hepatology, Female, Colorectal Neoplasms, Life Sciences & Biomedicine, EOCRC, Cohort study, medicine.medical_specialty, EPIDEMIOLOGY RESEARCH, Population, SNP, LYNCH-SYNDROME, Polymorphism, Single Nucleotide, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, education, Life Style, VLAG, Global Nutrition, Wereldvoeding, Science & Technology, Hepatology, Gastroenterology & Hepatology, Whole Genome Sequencing, business.industry, MUTATIONS, Case-control study, Cancer, 1103 Clinical Sciences, Odds ratio, medicine.disease, digestive system diseases, 030104 developmental biology, Case-Control Studies, LOW-PENETRANCE SUSCEPTIBILITY, 1114 Paediatrics and Reproductive Medicine, ADULT HEALTH, RACE/ETHNICITY, business, 1109 Neurosciences, Genome-Wide Association Study
Abstract: BACKGROUND & AIMS: Early-onset colorectal cancer (CRC, in persons younger than 50 years old) is increasing in incidence; yet, in the absence of a family history of CRC, this population lacks harmonized recommendations for prevention. We aimed to determine whether a polygenic risk score (PRS) developed from 95 CRC-associated common genetic risk variants was associated with risk for early-onset CRC. METHODS: We studied risk for CRC associated with a weighted PRS in 12,197 participants younger than 50 years old vs 95,865 participants 50 years or older. PRS was calculated based on single nucleotide polymorphisms associated with CRC in a large-scale genome-wide association study as of January 2019. Participants were pooled from 3 large consortia that provided clinical and genotyping data: the Colon Cancer Family Registry, the Colorectal Transdisciplinary Study, and the Genetics and Epidemiology of Colorectal Cancer Consortium and were all of genetically defined European descent. Findings were replicated in an independent cohort of 72,573 participants. RESULTS: Overall associations with CRC per standard deviation of PRS were significant for early-onset cancer, and were stronger compared with late-onset cancer (P for interaction = .01); when we compared the highest PRS quartile with the lowest, risk increased 3.7-fold for early-onset CRC (95% CI 3.28-4.24) vs 2.9-fold for late-onset CRC (95% CI 2.80-3.04). This association was strongest for participants without a first-degree family history of CRC (P for interaction = 5.61 × 10-5). When we compared the highest with the lowest quartiles in this group, risk increased 4.3-fold for early-onset CRC (95% CI 3.61-5.01) vs 2.9-fold for late-onset CRC (95% CI 2.70-3.00). Sensitivity analyses were consistent with these findings. CONCLUSIONS: In an analysis of associations with CRC per standard deviation of PRS, we found the cumulative burden of CRC-associated common genetic variants to associate with early-onset cancer, and to be more strongly associated with early-onset than late-onset cancer, particularly in the absence of CRC family history. Analyses of PRS, along with environmental and lifestyle risk factors, might identify younger individuals who would benefit from preventive measures.
Published: 2020

182. Meat intake and risk of gastric cancer in the Stomach cancer Pooling (StoP) project

Author: Shoichiro Tsugane, Bárbara Peleteiro, David Zaridze, Malaquías López-Cervantes, Ana Rute Costa, Eva Negri, Mary H. Ward, Domenico Palli, Reza Malekzadeh, Roberto Persiani, Ana Ferro, Paolo Boffetta, Rossella Bonzi, Raul U. Hernandez-Ramirez, Robert C. Kurtz, Jinfu Hu, Claudio Pelucchi, Jesús Vioque, Carlo La Vecchia, Valentina Rosato, Stefania Boccia, Gerson Shigueaki Hamada, Nuria Aragonés, M. Constanza Camargo, Vicente Martín, Matteo Rota, Kenneth C. Johnson, Nuno Lunet, Guo-Pei Yu, Pagona Lagiou, Paola Bertuccio, Dmitry Maximovitch, Samantha Morais, Monica Ferraroni, Farhad Pourfarzi, Lina Mu, Maria Paula Curado, Zuo-Feng Zhang, Lizbeth López-Carrillo, Eva María Navarrete-Muñoz, Areti Lagiou, Akihisa Hidaka, Ferro, Ana, Rosato, Valentina, Rota, Matteo, Costa, Ana Rute, Morais, Samantha, Pelucchi, Claudio, Johnson, Kenneth C, Hu, Jinfu, Palli, Domenico, Ferraroni, Monica, Zhang, Zuo-Feng, Bonzi, Rossella, Yu, Guo-Pei, Peleteiro, Bárbara, López-Carrillo, Lizbeth, Tsugane, Shoichiro, Hamada, Gerson Shigueaki, Hidaka, Akihisa, Zaridze, David, Maximovitch, Dmitry, Vioque, Jesu, Navarrete-Munoz, Eva M, Aragonés, Nuria, Martín, Vicente, Hernández-Ramírez, Raúl Ulise, Bertuccio, Paola, Ward, Mary H, Malekzadeh, Reza, Pourfarzi, Farhad, Mu, Lina, Lópes-Cervantes, Malaquia, Persiani, Roberto, Kurtz, Robert C, Lagiou, Areti, Lagiou, Pagona, Boffetta, Paolo, Boccia, Stefania, Negri, Eva, Camargo, M Constanza, Curado, Maria Paula, La Vecchia, Carlo, Lunet, Nuno, and Instituto de Saúde Pública da Universidade do Porto
Subjects: Adult, Male, Cancer Research, Meat, Settore MED/18 - CHIRURGIA GENERALE, Pooling, Oncology and Carcinogenesis, Article, Cohort Studies, 03 medical and health sciences, meat, 0302 clinical medicine, Clinical Research, medicine, Humans, Processed meat, Food science, Oncology & Carcinogenesis, Stomach cancer, Settore MED/42 - IGIENE GENERALE E APPLICATA, Meat intake, Aged, Cancer, stomach neoplasms, business.industry, pooled analysis, food and beverages, Odds ratio, Middle Aged, medicine.disease, diet, nutrition, Diet, Meat Products, Red Meat, Increased risk, Pooled analysi, Oncology, diet, meat, nutrition, pooled analysis, stomach neoplasms, 030220 oncology & carcinogenesis, Case-Control Studies, Red meat, Female, business
Abstract: The consumption of processed meat has been associated with noncardia gastric cancer, but evidence regarding a possible role of red meat is more limited. Our study aims to quantify the association between meat consumption, namely white, red and processed meat, and the risk of gastric cancer, through individual participant data meta-analysis of studies participating in the “Stomach cancer Pooling (StoP) Project”. Data from 22 studies, including 11,443 cases and 28,029 controls, were used. Study-specific odds ratios (ORs) were pooled through a two-stage approach based on random-effects models. An exposure-response relationship was modeled, using one and two-order fractional polynomials, to evaluate the possible nonlinear association between meat intake and gastric cancer. An increased risk of gastric cancer was observed for the consumption of all types of meat (highest vs. lowest tertile), which was statistically significant for red (OR: 1.24; 95% CI: 1.00–1.53), processed (OR: 1.23; 95% CI: 1.06–1.43) and total meat (OR: 1.30; 95% CI: 1.09–1.55). Exposure-response analyses showed an increasing risk of gastric cancer with increasing consumption of both processed and red meat, with the highest OR being observed for an intake of 150 g/day of red meat (OR: 1.85; 95% CI: 1.56–2.20). This work provides robust evidence on the relation between the consumption of different types of meat and gastric cancer. Adherence to dietary recommendations to reduce meat consumption may contribute to a reduction in the burden of gastric cancer. Our study was supported by the Associazione Italiana per la Ricerca sul Cancro (AIRC), Project no. 21378 (Investigator Grant), by the Italian Ministry of Health (Young Researchers, GR-2011-02347943 to SB), by the Italian League for the Fight Against Cancer (LILT) and by the Associazione Industriale delle Carni e dei Salumi (ASSICA, to the Department of Clinical Sciences and Community Health, University of Milan). Our study was also funded by FEDER through the Operational Programme Competitiveness and Internationalization and national funding from the Foundation for Science and Technology – FCT (Portuguese Ministry of Science, Technology and Higher Education) under the Unidade de Investigação em Epidemiologia – Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (POCI-01-0145-FEDER-006862; Ref. UID/DTP/04750/2013). AF (PD/BD/105823/2014) was awarded with an individual scholarship through national funding from FCT/MCTES. Individual grants attributed to ARC (SFRH/BD/102181/2014), and BP (SFRH/BPD/108751/2015) were funded by the FCT and the “Programa Operacional Capital Humano” (POCH/SE). SM was funded under the project “NEON-PC - Neuro-oncological complications of prostate cancer: longitudinal study of cognitive decline “ (POCI-01-0145-FEDER-032358; Ref. PTDC/SAU-EPI/32358/2017). Valentina Rosato was supported by a fellowship by the Italian Foundation for Cancer Research (FIRC #18104).
Published: 2020

183. Polyphenol Intake and Gastric Cancer Risk: Findings from the Stomach Cancer Pooling Project (StoP)

Author: María Rubín García, Paolo Boffetta, Domenico Palli, Nuno Lunet, Raúl U. Hernández-Ramírez, Monica Ferraroni, Areti Lagiou, Pagona Lagiou, Dmitry Maximovich, Nuria Aragonés, Maria Paula Curado, Malaquías López-Cervantes, Zuo-Feng Zhang, Gemma Castaño-Vinyals, Vicente Martín Sánchez, Jesús Vioque, Facundo Vitelli-Storelli, Matteo Rota, Claudio Pelucchi, Manuela García de la Hera, Mary H. Ward, M. Constanza Camargo, Carlo La Vecchia, Marta Rossi, Lizbeth López-Carrillo, Rossella Bonzi, Eva Negri, David Zaridze, Samantha Morais, F. Vitelli-Storelli, M. Rossi, C. Pelucchi, M. Rota, D. Palli, M. Ferraroni, N. Lunet, S. Morai, L. López-Carrillo, D. Georgievich Zaridze, D. Maximovich, M. Rubín García, G. Castaño-Vinyal, N. Aragoné, M. Garcia de la Hera, R. U. Hernández-Ramírez, E. Negri, R. Bonzi, M. H. Ward, A. Lagiou, P. Lagiou, M. López-Cervante, P. Boffetta, M. C. Camargo, M. P. Curado, Z. -F. Zhang, J. Vioque, C. La Vecchia, V. M. Sánchez, and Instituto de Saúde Pública da Universidade do Porto
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_specialty, Hydroxybenzoic acid, Epidemiology, Oncology and Carcinogenesis, Logistic regression, Gastroenterology, lcsh:RC254-282, Article, 03 medical and health sciences, 0302 clinical medicine, Flavonols, Clinical Research, Internal medicine, medicine, Diet, Flavonoids, Gastric cancer, Polyphenols, flavonoid, Stomach cancer, polyphenols, Nutrition, Cancer, chemistry.chemical_classification, 030109 nutrition & dietetics, business.industry, gastric cancer, Odds ratio, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Confidence interval, 3. Good health, Oncology, Quartile, chemistry, 030220 oncology & carcinogenesis, flavonoids, epidemiology, business, diet
Abstract: Phenolic compounds may exert a favorable effect on the risk of several cancer types, including gastric cancer (GC). However, selected polyphenol classes have not been adequately investigated in relation to GC. The aim of this study is to evaluate the association between the intake of polyphenols in relation to GC risk. We used data from the Stomach cancer Pooling (StoP) Project, including 10 studies from six countries (3471 GC cases and 8344 controls). We carried out an individual participant data pooled analysis using a two-stage approach. The summary odds ratios (ORs) of GC for each compound, and the corresponding 95% confidence intervals (95% CI), were computed by pooling study specific ORs obtained through multivariate logistic regression, using random effect models. Inverse associations with GC emerged for total polyphenols (OR = 0.67, 95% CI = 0.54&ndash, 0.81, for the highest versus lowest quartile of intake), total flavonoids (OR = 0.73, 95% CI = 0.55&ndash, 0.90), anthocyanidins (OR = 0.74, 95% CI = 0.56&ndash, 0.92), flavanols (OR = 0.77, 95% CI = 0.66&ndash, 0.88), flavanones (OR = 0.57, 95%CI = 0.44&ndash, 0.69), total phenolic acids (OR = 0.75, 95%CI = 0.55&ndash, 0.94), and hydroxybenzoic acids (OR = 0.73, 95%CI = 0.57&ndash, 0.89). Results were consistent across strata of age, sex, social class, and smoking habit. Suggestive inverse associations were also found for flavonols (OR = 0.76, 95%CI = 0.51&ndash, 1.01) and hydroxycinnamic acids (OR = 0.82, 95%CI = 0.58&ndash, 1.06). Further investigations from longitudinal data are needed to confirm this association.
Published: 2020

184. Meta-analysis of diagnostic performance of serological tests for SARS-CoV-2 antibodies up to 25 April 2020 and public health implications

Author: Federica Facciotti, Paolo Vineis, Luca Mazzarella, John Paget, Angelica Diaz-Basabe, Domenico Palli, Federica Corso, Gioacchino Natoli, Sara Raimondi, Federica Bellerba, Pier Giuseppe Pelicci, Sara Gandini, Simone Pietro De Angelis, Saverio Caini, Caini, S, Bellerba, F, Corso, F, Díaz-Basabe, A, Natoli, G, Paget, J, Facciotti, F, De Angelis, S, Raimondi, S, Palli, D, Mazzarella, L, Pelicci, P, Vineis, P, and Gandini, S
Subjects: 0301 basic medicine, serological tests, Epidemiology, specificity, Antibodies, Viral, Severe Acute Respiratory Syndrome, Immunoglobulin G, Serology, 0302 clinical medicine, COVID-19 Testing, systematic review, 030212 general & internal medicine, biology, Meta-analysis, Predictive value of tests, Antibody, Coronavirus Infections, Rapid Communication, medicine.medical_specialty, Coronaviridae Infections, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 030106 microbiology, Pneumonia, Viral, Sensitivity and Specificity, 03 medical and health sciences, Betacoronavirus, Predictive Value of Tests, Virology, Internal medicine, medicine, Humans, Serologic Tests, Pandemics, business.industry, SARS-CoV-2, Clinical Laboratory Techniques, Public health, Public Health, Environmental and Occupational Health, COVID-19, sensitivity, Coronavirus, meta-analysis, serological test, predictive values, Immunoglobulin M, SARS-CoV2, biology.protein, business
Abstract: We reviewed the diagnostic accuracy of SARS-CoV-2 serological tests. Random-effects models yielded a summary sensitivity of 82% for IgM, and 85% for IgG and total antibodies. For specificity, the pooled estimate were 98% for IgM and 99% for IgG and total antibodies. In populations with ≤ 5% of seroconverted individuals, unless the assays have perfect (i.e. 100%) specificity, the positive predictive value would be ≤ 88%. Serological tests should be used for prevalence surveys only in hard-hit areas.
Published: 2020

185. Urinary flavanone concentrations as biomarkers of dietary flavanone intakes in the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Author: Sabina Sieri, Yaiza Garro-Aguilar, Inge Huybrechts, Francesca Mancini, David Achaintre, Elisavet Valanou, Alessandra Macciotta, Verena Katzke, Maria Santucci de Magistris, Rosario Tumino, Heiner Boeing, Augustin Scalbert, Anna Karakatsani, Domenico Palli, Antonia Trichopoulou, Marie-Christine Boutron-Ruault, Iasim Tahiri, Valerie Cayssials, Raul Zamora-Ros, Tilman Kühn, Antonio Agudo, and Yahya Mahamat-Saleh
Subjects: 0301 basic medicine, Naringenin, Male, Urinary system, European Prospective Investigation into Cancer and Nutrition study, Medicine (miscellaneous), Physiology, 030209 endocrinology & metabolism, Urine, 03 medical and health sciences, chemistry.chemical_compound, Hesperidin, 0302 clinical medicine, Medicine, Humans, 030109 nutrition & dietetics, Nutrition and Dietetics, business.industry, Hesperetin, food and beverages, Middle Aged, Nutrition Surveys, Biomarkers, Flavanones, Intake, Citrus sinensis, Europe, Female, Nutrition Assessment, Diet, European Prospective Investigation into Cancer and Nutrition, chemistry, Biomarker (medicine), business, Flavanone
Abstract: In the present study, the aim was to investigate the correlation between the acute and habitual dietary intake of flavanones, their main food sources and the concentrations of aglycones naringenin and hesperetin in 24 h urine in a European population. A 24-h dietary recall (24-HDR) and a 24-h urine sample were collected the same day from a subsample of 475 people from four different countries of the European Prospective Investigation into Cancer and Nutrition study. Acute and habitual dietary data were captured through a standardised 24-HDR and a country/centre-specific validated dietary questionnaire (DQ). The intake of dietary flavanones was estimated using the Phenol-Explorer database. Urinary flavanones (naringenin and hesperetin) were analysed using tandem MS with a previous enzymatic hydrolysis. Weak partial correlation coefficients were found between urinary flavanone concentrations and both acute and habitual dietary flavanone intakes (Rpartial= 0·14–0·17). Partial correlations were stronger between urinary excretions and acute intakes of citrus fruit and juices (Rpartial∼ 0·6) than with habitual intakes of citrus fruit and juices (Rpartial∼ 0·24). In conclusion, according to our results, urinary excretion of flavanones can be considered a good biomarker of acute citrus intake. However, low associations between habitual flavanone intake and urinary excretion suggest a possible inaccurate estimation of their intake or a too sporadic intake. For assessing habitual exposures, multiple urinary collections may be needed. These results show that none of the approaches tested is ideal, and the use of both DQ and biomarkers can be recommended.
Published: 2020

186. Antibody Responses to Helicobacter pylori and Risk of Developing Colorectal Cancer in a European Cohort

Author: Kristin Benjaminsen Borch, Catherine Dong, Elisabete Weiderpass, Elio Riboli, Antonia Trichopoulou, Rudolf Kaaks, Claudia Agnoli, Michael Pawlita, Franck Carbonnel, Roel Vermeulen, Heiner Boeing, David J. Hughes, Amanda J. Cross, Julia Butt, Bethany Van Guelpen, Liher Imaz, Marc J. Gunter, Semi Zouiouich, José Ramón Quirós, Cecilie Kyrø, Mazda Jenab, Inger T. Gram, Aurora Perez-Cornago, Matthias B. Schulze, Alicia K Heath, Carlotta Sacerdote, Rosario Tumino, Eva Ardanaz, Jin Young Park, Carmen Santiuste, Anna Karakatsani, Domenico Palli, Tim Waterboer, Bas Bueno-de-Mesquita, Anne Tjønneland, Miguel Rodríguez-Barranco, Carlo La Vecchia, Antonio Agudo, Tilman Kühn, Marie-Christine Boutron-Ruault, Salvatore Panico, Sophia Harlid, Centre international de Recherche sur le Cancer (CIRC), 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), Institut Gustave Roussy (IGR), Mode de vie, génétique et santé : études intégratives et transgénérationnelles (U1018 (Équipe 9)), 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)-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)-Institut Gustave Roussy (IGR), and AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)
Subjects: 0301 basic medicine, Male, medicine.medical_specialty, Colorectal cancer, Epidemiology, [SDV]Life Sciences [q-bio], Gastroenterology, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Medicine, Humans, Helicobacter, Prospective Studies, Prospective cohort study, 11 Medical and Health Sciences, biology, Helicobacter pylori, business.industry, Cancer, Odds ratio, Middle Aged, biology.organism_classification, medicine.disease, bacterial infections and mycoses, digestive system diseases, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Case-Control Studies, Cohort, Antibody Formation, Female, business, Colorectal Neoplasms
Abstract: Background: While Helicobacter pylori (H. pylori) is the major cause of gastric cancer, it has also been suggested to be involved in colorectal cancer development. However, prospective studies addressing H. pylori and colorectal cancer are sparse and inconclusive. We assessed the association of antibody responses to H. pylori proteins with colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods: We applied H. pylori multiplex serology to measure antibody responses to 13 H. pylori proteins in prediagnostic serum samples from 485 colorectal cancer cases and 485 matched controls nested within the EPIC study. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable conditional logistic regression to estimate the association of H. pylori overall and protein-specific seropositivity with odds of developing colorectal cancer. Results: Fifty-one percent of colorectal cancer cases were H. pylori seropositive compared with 44% of controls, resulting in an OR of 1.36 (95% CI, 1.00–1.85). Among the 13 individual H. pylori proteins, the association was driven mostly by seropositivity to Helicobacter cysteine-rich protein C (HcpC; OR: 1.66; 95% CI, 1.19–2.30) and Vacuolating cytotoxin A (VacA) (OR: 1.34; 95% CI, 0.99–1.82), the latter being nonstatistically significant only in the fully adjusted model. Conclusions: In this prospective multicenter European study, antibody responses to H. pylori proteins, specifically HcpC and VacA, were associated with an increased risk of developing colorectal cancer. Impact: Biological mechanisms for a potential causal role of H. pylori in colorectal carcinogenesis need to be elucidated, and subsequently whether H. pylori eradication may decrease colorectal cancer incidence.
Published: 2020

187. Menstrual Factors, Reproductive History, Hormone Use, and Urothelial Carcinoma Risk: AProspective Study in the EPIC Cohort

Author: Aurora Perez-Cornago, Veronica Sciannameo, Salvatore Panico, Domenico Palli, Pilar Amiano, Marit Waaseth, Tilman Kühn, Kay-Tee Khaw, Tanja Stocks, Fredrik Liedberg, Lambertus A. Kiemeney, Carla H. van Gils, Anne Tjønneland, Neil Murphy, María José Sánchez, Leila Lujan-Barroso, Christel Häggström, Amanda J. Cross, Heiner Boeing, Bas Bueno-de-Mesquita, Raul Zamora-Ros, Nina Roswall, Marc J. Gunter, Renée T. Fortner, Inger T. Gram, Kim Overvad, Vittorio Krogh, Börje Ljungberg, Amalia Mattiello, Eric J. Duell, Saverio Caini, Antonia Trichopoulou, Elisabete Weiderpass, Virginia Menéndez, Iris Cervenka, Rosario Tumino, Carmen Santiuste, Agnès Fournier, Edoardo Botteri, Aurelio Barricarte, Eleni Peppa, Eiliv Lund, Marina Kvaskoff, N. Charlotte Onland-Moret, and Anna Karakatsani
Subjects: 0301 basic medicine, Oncology, Epidemiology, IMPACT, THERAPY, 0302 clinical medicine, Pregnancy, Risk Factors, Prospective Studies, Child, Prospective cohort study, Reproductive History, 11 Medical and Health Sciences, Bladder cancer, WOMEN, ASSOCIATION, European Prospective Investigation into Cancer and Nutrition, Menstruation, ESTROGEN, 030220 oncology & carcinogenesis, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Cohort, Female, SMOKING, Developed country, EXPRESSION, medicine.medical_specialty, Adolescent, Hormone Replacement Therapy, Càncer de bufeta, DIET, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, Internal medicine, medicine, Humans, Menstrual Cycle, VDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762, Proportional hazards model, business.industry, medicine.disease, Hormones, VDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762, 030104 developmental biology, BLADDER-CANCER RISK, SEX-HORMONES, business, Hormone, Menstruació
Abstract: Background: Urothelial carcinoma is the predominant (95%) bladder cancer subtype in industrialized nations. Animal and epidemiologic human studies suggest that hormonal factors may influence urothelial carcinoma risk. Methods: We used an analytic cohort of 333,919 women from the European Prospective Investigation into Cancer and Nutrition Cohort. Associations between hormonal factors and incident urothelial carcinoma (overall and by tumor grade, tumor aggressiveness, and non–muscle-invasive urothelial carcinoma) risk were evaluated using Cox proportional hazards models. Results: During a mean of 15 years of follow-up, 529 women developed urothelial carcinoma. In a model including number of full-term pregnancies (FTP), menopausal status, and menopausal hormone therapy (MHT), number of FTP was inversely associated with urothelial carcinoma risk (HR≥5vs1 = 0.48; 0.25–0.90; Ptrend in parous women = 0.010) and MHT use (compared with nonuse) was positively associated with urothelial carcinoma risk (HR = 1.27; 1.03–1.57), but no dose response by years of MHT use was observed. No modification of HRs by smoking status was observed. Finally, sensitivity analyses in never smokers showed similar HR patterns for the number of FTP, while no association between MHT use and urothelial carcinoma risk was observed. Association between MHT use and urothelial carcinoma risk remained significant only in current smokers. No heterogeneity of the risk estimations in the final model was observed by tumor aggressiveness or by tumor grade. A positive association between MTH use and non–muscle-invasive urothelial carcinoma risk was observed. Conclusions: Our results support that increasing the number of FTP may reduce urothelial carcinoma risk. Impact: More detailed studies on parity are needed to understand the possible effects of perinatal hormone changes in urothelial cells.
Published: 2020

188. Serologic markers of Chlamydia trachomatis and other sexually transmitted infections and subsequent ovarian cancer risk: Results from the EPIC cohort

Author: Agnès Fournier, Eva Lundin, N. Charlotte Onland-Moret, Louise Hansen, Elisavet Valanou, Marina Kvaskoff, Leire Gil, Inger T. Gram, Rosario Tumino, Marc J. Gunter, Annika Idahl, Rudolf Kaaks, Noemi Bender, Eric J. Duell, María José Sánchez, Carlotta Sacerdote, Kristian Riesbeck, Sandra González Maldonado, Claudia Agnoli, Anne Tjønneland, Charlotte Le Cornet, Renée T. Fortner, Laure Dossus, Marie-Christine Boutron-Ruault, Elisabete Weiderpass, Antonia Trichopoulou, Amalia Mattiello, José Ramón Quirós, Aurelio Barricarte, Maria Dolores Chirlaque, Tim Waterboer, Eleni Peppa, Domenico Palli, Jenny Brändstedt, Kay-Tee Khaw, Aurora Perez-Cornago, Heiner Boeing, Umeå University, Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, Danish Cancer Society Research Center, Copenhagen, Denmark, parent, 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), German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Hellenic Health Foundation, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Epidemiology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori, Via Venezian 1, I-20133 Milano, Italy, University of Naples Federico II, Civile - M.P.Arezzo Hospital, Center for Cancer Prevention (CPO-Piemonte), Universiteit Utrecht, Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway, Section of Cancer Surveillance, International Agency for Research on Cancer, Lyon, France. Electronic address: steliarova@iarc.fr., Catalan Institute of Oncology (ICO-IDIBELL), Hospitales Universitarios de Granada/Universidad de Granada, Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), CIBER de Epidemiología y Salud Pública (CIBERESP), IMIB-Arrixaca [Murcia, Spain], Universidad de Murcia, Public Health Institute of Navarra, Pamplona, Spain, and CIBER Epidemiología y Salud Pública (CIBERESP), IdiSNA, Navarra Institute for Health Research, Public Health Division of Gipuzkoa, Institute BIO Donostia-Health Department, Skane University Hospital [Lund], Department of Translational Medicine [Malmö, Sweden] (Clinical Microbiology), Lund University [Lund, Sweden], University of Cambridge [UK] (CAM), University of Oxford [Oxford], Ministerie van Volksgezondheid, Welzijn en Sport, VWS Deutsche Krebshilfe Cancer Research UK, CRUK: C8221/A19170, C570/A16491 VetenskapsrÃ¥det, VR Ministerie van Volksgezondheid, Welzijn en Sport, VWS Ligue Contre le Cancer Bundesministerium fÃ¼r Bildung und Forschung, BMBF Bundesministerium fÃ¼r Bildung und Forschung, BMBF Institut National de la Santé et de la Recherche Médicale, Inserm KrÃ¦ftens BekÃ¦mpelse, DCS CAN 2016/545 German Cancer Research Center, DKFZ National Research Council, NRC Cancer Research Foundation in Northern Sweden European Commission, EC Centre International de Recherche sur le Cancer, IARC RD06/0020 German Cancer Research Center, DKFZ Cancerfonden PI13/01162, PI13/00061 World Cancer Research Fund, WCRF: ERC-2009-AdG 232997 NordForsk Associazione Italiana per la Ricerca sul Cancro, AIRC Medical Research Council, MRC: MR/M012190/1, This work was supported by grants from The Cancer Research Foundation in Northern Sweden and The County Council of V?sterbotten, Sweden, and the German Cancer Research Center. 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 G?n?rale de l'Education Nationale, Institut National de la Sant? et de la Recherche M?dicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), 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 Andaluc?a, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Sk?ne and V?sterbotten (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). Additional funding received from the Anna and Edwin Berger Foundation (K.R.), Malm? Hospital Cancer Foundation (K.R.), Cancerfonden (CAN 2016/545 to K.R.).
Subjects: Oncology, Cancer Research, endocrine system diseases, Càncer d'ovari, Chlamydia trachomatis, Mycoplasma genitalium, Carcinoma, Ovarian Epithelial, medicine.disease_cause, Serology, 0302 clinical medicine, Risk Factors, Pelvic inflammatory disease, Prospective Studies, human papillomavirus, Aged, 80 and over, Ovarian Neoplasms, Sexually transmitted diseases, Human papillomavirus 16, Chlamydia, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, biology, Public Health, Global Health, Social Medicine and Epidemiology, Middle Aged, female genital diseases and pregnancy complications, 3. Good health, Serous fluid, ovarian cancer, 030220 oncology & carcinogenesis, Female, Malalties de transmissió sexual, Adult, Risk, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Ovarian cancer, Internal medicine, medicine, Humans, Neoplastic transformation, Aged, business.industry, Papillomavirus Infections, Chlamydia Infections, biology.organism_classification, medicine.disease, herpes simplex virus, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Relative risk, Case-Control Studies, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business, Biomarkers
Abstract: International audience; A substantial proportion of epithelial ovarian cancer (EOC) arises in the fallopian tube and other epithelia of the upper genital tract; these epithelia may incur damage and neoplastic transformation after sexually transmitted infections (STI) and pelvic inflammatory disease. We investigated the hypothesis that past STI infection, particularly Chlamydia trachomatis, is associated with higher EOC risk in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort including 791 cases and 1669 matched controls. Serum antibodies against C. trachomatis, Mycoplasma genitalium, herpes simplex virus type 2 (HSV-2) and human papillomavirus (HPV) 16, 18 and 45 were assessed using multiplex fluorescent bead-based serology. Conditional logistic regression was used to estimate relative risks (RR) and 95% confidence intervals (CI) comparing women with positive vs. negative serology. A total of 40% of the study population was seropositive to at least one STI. Positive serology to C. trachomatis Pgp3 antibodies was not associated with EOC risk overall, but with higher risk of the mucinous histotype (RR = 2.30 [95% CI = 1.22-4.32]). Positive serology for chlamydia heat shock protein 60 (cHSP60-1) was associated with higher risk of EOC overall (1.36 [1.13-1.64]) and with the serous subtype (1.44 [1.12-1.85]). None of the other evaluated STIs were associated with EOC risk overall; however, HSV-2 was associated with higher risk of endometrioid EOC (2.35 [1.24-4.43]). The findings of our study suggest a potential role of C. trachomatis in the carcinogenesis of serous and mucinous EOC, while HSV-2 might promote the development of endometrioid disease.
Published: 2020

189. Adult height and risk of gastric cancer: a pooled analysis within the Stomach cancer Pooling Project

Author: Kenneth C. Johnson, Zuo-Feng Zhang, Reza Malekzadeh, Areti Lagiou, Carlo La Vecchia, Jovana Stojanovic, Nuno Lunet, Roberta Pastorino, Nuria Aragonés, Pagona Lagiou, Eva María Navarrete-Muñoz, Robert C. Kurtz, Dario Arzani, Roberto Persiani, Stefania Boccia, Guo-Pei Yu, Ana Ferro, Luca Giraldi, Claudio Pelucchi, Farhad Pourfarzi, David Zaridze, Lina Mu, Mohammadreza Pakseresht, Joshua E. Muscat, Monica Ferraroni, Matteo Rota, Dmitry Maximovich, Jesús Vioque, Eva Negri, Jinfu Hu, Domenico Palli, Vicente Martín, Giraldi, Luca, Stojanovic, Jovana, Arzani, Dario, Persiani, Roberto, Hu, Jinfu, Johnson, Kenneth C, Zhang, Zuo-Feng, Ferraroni, Monica, Palli, Domenico, Yu, Guo-Pei, La Vecchia, Carlo, Pelucchi, Claudio, Lunet, Nuno, Ferro, Ana, Malekzadeh, Reza, Muscat, Joshua, Zaridze, David, Maximovich, Dmitry, Aragones, Nuria, Martin, Vicente, Vioque, Jesù, Navarrete-Munoz, Eva M, Pakseresht, Mohammadreza, Negri, Eva, Rota, Matteo, Pourfarzi, Farhad, Mu, Lina, Kurtz, Robert C, Lagiou, Areti, Lagiou, Pagona, Pastorino, Roberta, and Boccia, Stefania
Subjects: Cancer Research, medicine.medical_specialty, biology, Epidemiology, business.industry, gastric cancer, Public Health, Environmental and Occupational Health, Cancer, Regression analysis, Odds ratio, Helicobacter pylori, medicine.disease, biology.organism_classification, Logistic regression, Confidence interval, Oncology, Medicine, adult height, business, Stomach cancer, Settore MED/42 - IGIENE GENERALE E APPLICATA, Demography
Abstract: BACKGROUND: The association between height and risk of gastric cancer has been studied in several epidemiological studies with contrasting results. The aim of this study is to examine the association between adult height and gastric cancer within a large pooled analysis of case-control studies members of the Stomach cancer Pooling (StoP) Project consortium. METHODS: Data from 18 studies members of the StoP consortium were collected and analyzed. A multivariable logistic regression model was used to estimate the study-specific odds ratios (ORs) and 95% confidence intervals (CIs) for the association between 10-cm increase in height and risk of gastric cancer. Age, sex, tobacco smoking, alcohol consumption, social class, geographical area and Helicobacter pylori (H. pylori) status were included in the regression model. Resulting estimates were then pooled with random-effect model. Analyses were conducted overall and in strata of selected variables. RESULTS: A total of 7562 cases and 19 033 controls were included in the analysis. The pooled OR was 0.96 (95% CI 0.87-1.05). A sensitivity analysis was performed restricting the results to the studies with information on H. pylori status, resulting in an OR of 0.97 (95% CI 0.79-1.20). CONCLUSION: Our study does not support a strong and consistent association between adult height and gastric cancer.
Published: 2020

190. Lifestyle factors and risk of multimorbidity of cancer and cardiometabolic diseases: A multinational cohort study

Author: Manuela M. Bergmann, Elio Riboli, Christina C. Dahm, Marc J. Gunter, Christina Bamia, David C. Muller, Pauline Bazelle, Antonio Agudo, Isabelle Romieu, Heather Ward, Pietro Ferrari, Patrick Arveux, Anja Olsen, Tammy Y.N. Tong, Elin Thysell, Julie A. Schmidt, María José Sánchez, Adam S. Butterworth, Aurelio Barricarte Gurrea, Peter Nilsson, Pilar Amiano, Kim Overvad, Fulvio Ricceri, Rosario Tumino, Salvatore Panico, Michael J. Sweeting, Evelyn M. Monninkhof, Anne Tjønneland, Marina Kvaskoff, Vincenzo Bagnardi, Olov Rolandsson, Konstantinos K. Tsilidis, Mazda Jenab, H. Susan J. Picavet, Paolo Vineis, Tilman Kühn, Heinz Freisling, Gianluca Severi, John Danesh, Claudia Agnoli, Hannah Lennon, Marije F. Bakker, Vivian Viallon, Virginia Menéndez, Rudolf Kaaks, Nicholas J. Wareham, Heiner Boeing, Carmen Santiuste, Jonas Manjer, Elisabete Weiderpass, Domenico Palli, Ioanna Tzoulaki, Cristian Ricci, 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), 2018-1-PL SHS-06-CIRC-1 LSHM_CT_2006_037197 HEALTH24 F2-2012-279233 PI13/00061, PI13/01162 2018-123 RD06/0020 G0800270, MR/ L003120/1 Kræftens Bekæmpelse, DCS German Cancer Research Center, DKFZ Centre International de Recherche sur le Cancer, IARC National Research Council, NRC Medical Research Council, MRC: MR/M012190/1 British Heart Foundation, BHF: 26 RG/08/014, RG13/ 13/30194, SP/09/002 Cancer Research UK, CRUK: C570/A16491, C8221/A19170 World Cancer Research Fund, WCRF European Commission, EC European Research Council, ERC: 268834 Bundesministerium für Bildung und Forschung, BMBF Cancerfonden Ministerie van Volksgezondheid, Welzijn en Sport, VWS Vetenskapsrådet, VR Ministère des Affaires Sociales et de la Santé: GR-IARC-2003-09-12-01 Direction Générale de la Compétitivité, de l’Industrie et des Services, DGCIS Associazione Italiana per la Ricerca sul Cancro, AIRC Deutsche Krebshilfe, This work was supported by the Direction Générale de la Santé (French Ministry of Health) (Grant GR-IARC-2003-09-12-01) and by the French National Cancer Institute (INCA_N°2018-123), and the Cancéropôle Ile-de-France (N°2018-1-PL SHS-06-CIRC-1). Funding for the InterAct project was provided by the EU FP6 programme (grant no. LSHM_CT_2006_037197). EPIC-CVD has been supported by the European Union Framework 7 (HEALTH24 F2-2012-279233), the European Research Council (268834), the UK Medical Research 25 Council (G0800270 and MR/ L003120/1), the British Heart Foundation (SP/09/002 and 26 RG/08/014 and RG13/ 13/30194), and the UK National Institute of Health Research. 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), 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), 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), 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 (Sweden), Cancer Research UK (14136 to EPIC-Norfolk, C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (UK). The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report., Butterworth, Adam [0000-0002-6915-9015], Danesh, John [0000-0003-1158-6791], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Cancer Research UK, Freisling, H, Viallon, V, Lennon, H, Bagnardi, V, Ricci, C, Butterworth, A, Sweeting, M, Muller, D, Romieu, I, Bazelle, P, Kvaskoff, M, Arveux, P, Severi, G, Bamia, C, Kuhn, T, Kaaks, R, Bergmann, M, Boeing, H, Tjonneland, A, Olsen, A, Overvad, K, Dahm, C, Menendez, V, Agudo, A, Sanchez, M, Amiano, P, Santiuste, C, Gurrea, A, Tong, T, Schmidt, J, Tzoulaki, I, Tsilidis, K, Ward, H, Palli, D, Agnoli, C, Tumino, R, Ricceri, F, Panico, S, Picavet, H, Bakker, M, Monninkhof, E, Nilsson, P, Manjer, J, Rolandsson, O, Thysell, E, Weiderpass, E, Jenab, M, Riboli, E, Vineis, P, Danesh, J, Wareham, N, Gunter, M, Ferrari, P, 29790514 - Ricci, Cristian, Overvad, Kim [0000-0001-6429-7921], Dahm, Christina C [0000-0003-0481-2893], and Tong, Tammy Y N [0000-0002-0284-8959]
Subjects: Male, lcsh:Medicine, Disease, Diabete, Body Mass Index, Cohort Studies, 0302 clinical medicine, Risk Factors, Neoplasms, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, Càncer, 11 Medical and Health Sciences, Cancer, 2. Zero hunger, Medicine(all), Incidence, Hazard ratio, Diabetes, General Medicine, Middle Aged, Cardiovascular disease, 3. Good health, Cardiovascular diseases, Cardiovascular Diseases, 030220 oncology & carcinogenesis, Obesitat, Female, Type 2, Cohort study, Research Article, Adult, Alcohol Drinking, Cancer and cardiometabolic multimorbidity, Healthy lifestyle, Obesity, Prevention, Diabetes Mellitus, Type 2, Humans, Proportional Hazards Models, Risk Reduction Behavior, Life Style, Multimorbidity, 03 medical and health sciences, Environmental health, General & Internal Medicine, medicine, Journal Article, Diabetes Mellitus, Cancer och onkologi, business.industry, Proportional hazards model, Malalties cardiovasculars, lcsh:R, medicine.disease, Cancer and Oncology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Body mass index
Abstract: Background Although lifestyle factors have been studied in relation to individual non-communicable diseases (NCDs), their association with development of a subsequent NCD, defined as multimorbidity, has been scarcely investigated. The aim of this study was to investigate associations between five lifestyle factors and incident multimorbidity of cancer and cardiometabolic diseases. Methods In this prospective cohort study, 291,778 participants (64% women) from seven European countries, mostly aged 43 to 58 years and free of cancer, cardiovascular disease (CVD), and type 2 diabetes (T2D) at recruitment, were included. Incident multimorbidity of cancer and cardiometabolic diseases was defined as developing subsequently two diseases including first cancer at any site, CVD, and T2D in an individual. Multi-state modelling based on Cox regression was used to compute hazard ratios (HR) and 95% confidence intervals (95% CI) of developing cancer, CVD, or T2D, and subsequent transitions to multimorbidity, in relation to body mass index (BMI), smoking status, alcohol intake, physical activity, adherence to the Mediterranean diet, and their combination as a healthy lifestyle index (HLI) score. Cumulative incidence functions (CIFs) were estimated to compute 10-year absolute risks for transitions from healthy to cancer at any site, CVD (both fatal and non-fatal), or T2D, and to subsequent multimorbidity after each of the three NCDs. Results During a median follow-up of 11 years, 1910 men and 1334 women developed multimorbidity of cancer and cardiometabolic diseases. A higher HLI, reflecting healthy lifestyles, was strongly inversely associated with multimorbidity, with hazard ratios per 3-unit increment of 0.75 (95% CI, 0.71 to 0.81), 0.84 (0.79 to 0.90), and 0.82 (0.77 to 0.88) after cancer, CVD, and T2D, respectively. After T2D, the 10-year absolute risks of multimorbidity were 40% and 25% for men and women, respectively, with unhealthy lifestyle, and 30% and 18% for men and women with healthy lifestyles. Conclusion Pre-diagnostic healthy lifestyle behaviours were strongly inversely associated with the risk of cancer and cardiometabolic diseases, and with the prognosis of these diseases by reducing risk of multimorbidity.
Published: 2020

191. Coffee and tea consumption and risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition

Author: Aurelio Barricarte, Tilman Kühn, Nikos Papadimitriou, Rosario Tumino, Elio Riboli, Lena Maria Nilsson, Dimitrios Trichopoulos, Dagfinn Aune, Bas Bueno-de-Mesquita, Kim Overvad, Ruth C. Travis, Nerea Larrañaga, Bodil Hammer Bech, Peter Wallström, Antonia Trichopoulou, Christina Bamia, Maria Luisa Redondo, Heiner Boeing, Valerie Cayssials, Rudolf Kaaks, Carlotta Sacerdote, Anne Tjønneland, Ioanna Tzoulaki, Neil Murphy, Anna Karakatsani, Aurora Perez-Cornago, Rikard Landberg, Anastasia Kotanidou, Cecilie Kyrø, Sara Grioni, Pagona Lagiou, Saverio Caini, David S. Lopez, Heinz Freisling, Maria Dolores Chirlaque, Amanda J. Cross, Kay-Tee Khaw, Isabel Drake, Timothy J. Key, Konstantinos K. Tsilidis, Domenico Palli, Marc J. Gunter, David C. Muller, Abhijit Sen, Malene Outzen, Manuela M. Bergmann, and María José Sánchez
Subjects: Cancer Research, medicine.medical_specialty, business.industry, Proportional hazards model, Incidence (epidemiology), Hazard ratio, Cancer, medicine.disease, European Prospective Investigation into Cancer and Nutrition, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Internal medicine, Epidemiology, medicine, business, Cohort study
Abstract: The epidemiological evidence regarding the association of coffee and tea consumption with prostate cancer risk is inconclusive, and few cohort studies have assessed these associations by disease stage and grade. We examined the associations of coffee (total, caffeinated and decaffeinated) and tea intake with prostate cancer risk in the European Prospective Investigation into Cancer and Nutrition. Among 142,196 men, 7,036 incident prostate cancer cases were diagnosed over 14 years of follow-up. Data on coffee and tea consumption were collected through validated country-specific food questionnaires at baseline. We used Cox proportional hazards regression models to compute hazard ratios (HRs) and 95% confidence intervals (CI). Models were stratified by center and age, and adjusted for anthropometric, lifestyle and dietary factors. Median coffee and tea intake were 375 and 106 mL/day, respectively, but large variations existed by country. Comparing the highest (median of 855 mL/day) versus lowest (median of 103 mL/day) consumers of coffee and tea (450 vs. 12 mL/day) the HRs were 1.02 (95% CI, 0.94–1.09) and 0.98 (95% CI, 0.90–1.07) for risk of total prostate cancer and 0.97 (95% CI, 0.79–1.21) and 0.89 (95% CI, 0.70–1.13) for risk of fatal disease, respectively. No evidence of association was seen for consumption of total, caffeinated or decaffeinated coffee or tea and risk of total prostate cancer or cancer by stage, grade or fatality in this large cohort. Further investigations are needed to clarify whether an association exists by different preparations or by concentrations and constituents of these beverages.
Published: 2018

192. Blood levels of cadmium and lead in relation to breast cancer risk in three prospective cohorts

Author: Lauren R. Teras, W. Ryan Diver, Susan M. Gapstur, Emily L. Deubler, Soterios A. Kyrtopoulos, James M. Hodge, Mia M. Gaudet, Ingvar A. Bergdahl, Rachel S. Kelly, Paolo Vineis, Keith E. Levine, Laura G. Haines, Per Lenner, Thomas Lundh, and Domenico Palli
Subjects: Oncology, Cancer Research, medicine.medical_specialty, education.field_of_study, business.industry, education, Population, Case-control study, Cancer, Environmental exposure, medicine.disease, Persistence (computer science), 03 medical and health sciences, 0302 clinical medicine, Breast cancer, 030220 oncology & carcinogenesis, Internal medicine, medicine, business, Prospective cohort study, Carcinogen
Abstract: Cadmium and lead have been classified as carcinogens by the International Agency for Research on Cancer. However, their associations with breast cancer risk are unknown despite their persistence in ...
Published: 2018

193. Antibody Responses to

Author: Julia, Butt, Mazda, Jenab, Michael, Pawlita, Anne, Tjønneland, Cecilie, Kyrø, Marie-Christine, Boutron-Ruault, Franck, Carbonnel, Catherine, Dong, Rudolf, Kaaks, Tilman, Kühn, Heiner, Boeing, Matthias B, Schulze, Antonia, Trichopoulou, Anna, Karakatsani, Carlo, La Vecchia, Domenico, Palli, Claudia, Agnoli, Rosario, Tumino, Carlotta, Sacerdote, Salvatore, Panico, Bas, Bueno-de-Mesquita, Roel, Vermeulen, Inger T, Gram, Elisabete, Weiderpass, Kristin Benjaminsen, Borch, Jose Ramón, Quirós, Antonio, Agudo, Miguel, Rodríguez-Barranco, Carmen, Santiuste, Eva, Ardanaz, Bethany, Van Guelpen, Sophia, Harlid, Liher, Imaz, Aurora, Perez-Cornago, Marc J, Gunter, Semi, Zouiouich, Jin Young, Park, Elio, Riboli, Amanda J, Cross, Alicia K, Heath, Tim, Waterboer, and David J, Hughes
Subjects: Cohort Studies, Europe, Male, Helicobacter pylori, Risk Factors, Case-Control Studies, Antibody Formation, Humans, Female, Prospective Studies, Middle Aged, Colorectal Neoplasms
Abstract: WhileWe appliedFifty-one percent of colorectal cancer cases wereIn this prospective multicenter European study, antibody responses toBiological mechanisms for a potential causal role of
Published: 2019

194. 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

195. Smoking and FGFR2 rs2981582 variant independently modulate male breast cancer survival: A population-based study in Tuscany, Italy

Author: Laura Ottini, Piera Rizzolo, Ines Zanna, Vania Vezzosi, Giovanna Masala, Veronica Zelli, Virginia Valentini, Valentina Silvestri, Simonetta Bianchi, Benedetta Bendinelli, Domenico Palli, Calogero Saieva, and Alessandro Magrini
Subjects: Male, 0301 basic medicine, Oncology, Multivariate analysis, Survival, Genes, BRCA2, Genes, BRCA1, Kaplan-Meier Estimate, Breast cancer, Cigarette smoking, FGFR2, Population-based study, Adult, Aged, Aged, 80 and over, Breast Neoplasms, Male, Cigarette Smoking, Genetic Association Studies, Genetic Predisposition to Disease, Genotype, Humans, Italy, Middle Aged, Multivariate Analysis, Polymorphism, Single Nucleotide, Proportional Hazards Models, Receptor, Fibroblast Growth Factor, Type 2, Regression Analysis, Young Adult, Surgery, 0302 clinical medicine, Medicine, Young adult, education.field_of_study, General Medicine, 030220 oncology & carcinogenesis, Male breast cancer, medicine.medical_specialty, Population, 03 medical and health sciences, Statistical significance, Internal medicine, education, Survival analysis, business.industry, Proportional hazards model, medicine.disease, 030104 developmental biology, business
Abstract: Aim Male breast cancer (MBC) is a rare disease and recommendations for its clinical management are often extrapolated from those for female breast cancer, even if breast cancer (BC) has different characteristics in the two sexes. The purpose of this study was to assess the influence of several individual characteristics including clinico-pathological, lifestyle and genetic factors on overall survival (OS) of a relatively large and well characterized population-based series of 166 MBCs enrolled in Tuscany. Methods We genotyped MBC cases at BRCA1/2 genes and at 9 candidate BC susceptibility SNPs. Kaplan-Meier method and multivariate Cox regression, adjusted for several individual characteristics were used. To reduce a possible selection bias related to the interval between diagnosis and enrolment of MBC cases into the study, we used the date of blood donation as the date of the start of observation for survival analysis. Results Only smoking habits had a significant effect on OS at 10 years (for current smokers, HR: 3.34; 95% CI 1.45–7.68; p = 0.004), while lymph node status fell short of reaching statistical significance (for pN positive, HR: 2.07; 95% CI 0.93–4.55; p = 0.07). In the same multivariate analysis we found a significantly higher OS in cases with FGFR2 rs2981582 variant in the dominant transmission model (HR: 0.29; 95% CI: 0.13–0.62; p = 0.028). A sensitivity analysis with left truncation showed similar results. Conclusions Our results may contribute to shed light on factors influencing MBC survival suggesting an important role for cigarette smoking and FGFR2 rs2981582 variant, and provide clues for better patient management.
Published: 2018

196. Lifetime and baseline alcohol intakes and risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition study

Author: Androniki Naska, Kim Overvad, Kuanrong Li, Eric J. Duell, Domenico Palli, Giovanna Tagliabue, Christina Bamia, Ingegerd Johansson, Petra H.M. Peeters, Nicholas J. Wareham, Anne Tjønneland, Paul Brennan, Bas Bueno-de-Mesquita, Kathryn E. Bradbury, Antonia Trichopoulou, Miguel Rodríguez-Barranco, Guri Skeie, Marie-Christine Boutron-Ruault, Salvatore Panico, Franco Berrino, Rosario Tumino, Verena Katzke, Marc J. Gunter, Sabine Naudin, Elisabete Weiderpass Vainio, Pietro Ferrari, Inger T. Gram, Anne Laure Védié, Elio Riboli, Aurelio Barricarte, Miren Dorronsoro, Nada Assi, Tristan Jaouen, José Ramón Quirós, Rudolf Kaaks, Heiner Boeing, Maria Dolores Chirlaque, Malin Sund, Hanna Sternby, Carlotta Sacerdote, Vinciane Rebours, and Cecilie Kyrø
Subjects: 0301 basic medicine, Cancer Research, business.industry, Hazard ratio, Alcohol, medicine.disease, Confidence interval, European Prospective Investigation into Cancer and Nutrition, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, 0302 clinical medicine, Oncology, chemistry, 030220 oncology & carcinogenesis, Pancreatic cancer, Medicine, Smoking status, business, Prospective cohort study, Wine intake, Demography
Abstract: Recent evidence suggested a weak relationship between alcohol consumption and pancreatic cancer (PC) risk. In our study, the association between lifetime and baseline alcohol intakes and the risk of PC was evaluated, including the type of alcoholic beverages and potential interaction with smoking. Within the European Prospective Investigation into Cancer and Nutrition (EPIC) study, 1,283 incident PC (57% women) were diagnosed from 476,106 cancer-free participants, followed up for 14 years. Amounts of lifetime and baseline alcohol were estimated through lifestyle and dietary questionnaires, respectively. Cox proportional hazard models with age as primary time variable were used to estimate PC hazard ratios (HR) and their 95% confidence interval (CI). Alcohol intake was positively associated with PC risk in men. Associations were mainly driven by extreme alcohol levels, with HRs comparing heavy drinkers (>60 g/day) to the reference category (0.1-4.9 g/day) equal to 1.77 (95% CI: 1.06, 2.95) and 1.63 (95% CI: 1.16, 2.29) for lifetime and baseline alcohol, respectively. Baseline alcohol intakes from beer (>40 g/day) and spirits/liquors (>10 g/day) showed HRs equal to 1.58 (95% CI: 1.07, 2.34) and 1.41 (95% CI: 1.03, 1.94), respectively, compared to the reference category (0.1-2.9 g/day). In women, HR estimates did not reach statistically significance. The alcohol and PC risk association was not modified by smoking status. Findings from a large prospective study suggest that baseline and lifetime alcohol intakes were positively associated with PC risk, with more apparent risk estimates for beer and spirits/liquors than wine intake.
Published: 2018

197. Tumor-associated autoantibodies as early detection markers for ovarian cancer? A prospective evaluation

Author: Sabina Sieri, Dagfinn Aune, Inger T. Gram, Karin Jirström, Kim Overvad, Renée T. Fortner, Rudolf Kaaks, Carlo La Vecchia, Carmen Navarro Sánchez, Rosario Tumino, Eric J. Duell, María José Sánchez, N. Charlotte Onland-Moret, Anika Hüsing, Domenico Palli, Ruth C. Travis, Antonia Trichopoulou, Theron Johnson, Anne Tjønneland, Laure Dossus, Melissa A. Merritt, Vassiliki Benetou, Elisabete Weiderpass, Agnès Fournier, Nerea Larrañaga, Kathryn L. Terry, Eva Ardanaz, Amalia Mattiello, Annika Idahl, Eva Lundin, Louise Hansen, Elio Riboli, Marina Kvaskoff, Karen S. Anderson, Giuseppe Matullo, Björn Nodin, Marie-Christine Boutron-Ruault, Mattias Johansson, Myrto Barrdahl, Heiner Boeing, Daniel W. Cramer, and Marika Hopper
Subjects: 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, endocrine system diseases, biology, business.industry, Case-control study, Autoantibody, medicine.disease, 03 medical and health sciences, Serous fluid, 030104 developmental biology, 0302 clinical medicine, Antigen, 030220 oncology & carcinogenesis, Internal medicine, Cohort, medicine, biology.protein, Antibody, Ovarian cancer, business, Prospective cohort study
Abstract: Immuno-proteomic screening has identified several tumor-associated autoantibodies (AAb) that may have diagnostic capacity for invasive epithelial ovarian cancer, with AAbs to P53 proteins and cancer-testis antigens (CTAGs) as prominent examples. However, the early detection potential of these AAbs has been insufficiently explored in prospective studies. We performed ELISA measurements of AAbs to CTAG1A, CTAG2, P53 and NUDT11 proteins, for 194 patients with ovarian cancer and 705 matched controls from the European EPIC cohort, using serum samples collected up to 36 months prior to diagnosis under usual care. CA125 was measured using electrochemo-luminiscence. Diagnostic discrimination statistics were calculated by strata of lead-time between blood collection and diagnosis. With lead times ≤6 months, ovarian cancer detection sensitivity at 0.98 specificity (SE98) varied from 0.19 [95% CI 0.08-0.40] for CTAG1A, CTAG2 and NUDT1 to 0.23 [0.10-0.44] for P53 (0.33 [0.11-0.68] for high-grade serous tumors). However, at longer lead-times, the ability of these AAb markers to distinguish future ovarian cancer cases from controls declined rapidly; at lead times >1 year, SE98 estimates were close to zero (all invasive cases, range: 0.01-0.11). Compared to CA125 alone, combined logistic regression scores of AAbs and CA125 did not improve detection sensitivity at equal level of specificity. The added value of these selected AAbs as markers for ovarian cancer beyond CA125 for early detection is therefore limited.
Published: 2018

198. Prediagnostic Serum Vitamin D Levels and the Risk of Crohn’s Disease and Ulcerative Colitis in European Populations: A Nested Case-Control Study

Author: Tilman Kühn, Eef G.W.M. Lentjes, Petra H.M. Peeters, Kay-Tee Khaw, Domenico Palli, Andrew Hart, Anne Tjønneland, Anja Olsen, Kim Overvad, Ben J.M. Witteman, Manuela M. Bergmann, Robert Luben, Giovanna Masala, Antoine Racine, Marie-Christine Boutron-Ruault, Timothy J. Key, Rosario Tumino, W M Monique Verschuren, Vibeke Andersen, Simon S. M. Chan, Bas Oldenburg, Peter D. Siersema, Franck Carbonnel, Fiona D.M. van Schaik, Heiner Boeing, Antonia Trichopoulou, Jorrit L. Opstelten, and Rudolf Kaaks
Subjects: 0301 basic medicine, medicine.medical_specialty, etiology, Gastroenterology, Inflammatory bowel disease, vitamin D deficiency, Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14], 03 medical and health sciences, 0302 clinical medicine, inflammatory bowel disease, Internal medicine, Journal Article, medicine, Vitamin D and neurology, Immunology and Allergy, Vitamin D, Prospective cohort study, Human Nutrition & Health, ulcerative colitis, Crohn's disease, business.industry, Humane Voeding & Gezondheid, Case-control study, medicine.disease, digestive system diseases, European Prospective Investigation into Cancer and Nutrition, 030104 developmental biology, Nested case-control study, 030211 gastroenterology & hepatology, business
Abstract: Background: A low vitamin D status has been put forward as a potential risk factor for the development of inflammatory bowel disease (IBD). This study investigated the association between prediagnostic circulating vitamin D concentrations and dietary intakes of vitamin D, and the risk of Crohn’s disease (CD) and ulcerative colitis (UC).Methods: Among 359,728 participants of the European Prospective Investigation into Cancer and Nutrition cohort, individuals who developed CD or UC after enrollment were identified. Each case was matched with2 controls by center, gender, age, date of recruitment, and follow-up time. At cohort entry, blood samples were collected and dietary vitamin D intakes were obtained from validated food frequency questionnaires. Serum 25-hydroxyvitamin D levels were measured using liquid chromatography-tandem mass spectrometry. Conditional logistic regression was performed to determine the odds of CD and UC.Results: Seventy-two participants developed CD and 169 participants developed UC after a median follow-up of 4.7 and 4.1 years, respectively. Compared with the lowest quartile, no associations with the 3 higher quartiles of vitamin D concentrations were observed for CD (p trend = 0.34) or UC (p trend = 0.66). Similarly, no associations were detected when serum vitamin D levels were analyzed as a continuous variable. Dietary vitamin D intakes were not associated with CD (p trend = 0.39) or UC (p trend = 0.83).Conclusions: Vitamin D status was not associated with the development of CD or UC. This does not suggest a major role for vitamin D deficiency in the etiology of IBD, although larger studies are needed to confirm these findings.
Published: 2018

199. Prospective evaluation of antibody response toStreptococcus gallolyticusand risk of colorectal cancer

Author: Kathryn E. Bradbury, Carlo La Vecchia, Elisabete Weiderpass, Domenico Palli, Dagfinn Aune, Gianluca Severi, Eva Ardanaz, Michael Pawlita, Salvatore Panico, José María Huerta, H. Bas Bueno-de-Mesquita, María José Sánchez, Martina Willhauck-Fleckenstein, Anna Karakatsani, Kostas Tsilidis, Rosario Tumino, Franck Carbonnel, Marc J. Gunter, Angelika Michel, Carlotta Sacerdote, Mazda Jenab, Cecilie Kyrø, Heinz Freisling, Heiner Boeing, Claudia Agnoli, Rudolf Kaaks, Antonia Trichopoulou, Elio Riboli, Julia Butt, David J. Hughes, Tim Waterboer, Anne Tjønneland, Tilman Kühn, Catalina Bonet, Neil Murphy, and Marie-Christine Boutron-Ruault
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_specialty, biology, Colorectal cancer, business.industry, Case-control study, Cancer, Odds ratio, medicine.disease, Gastroenterology, Serology, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Internal medicine, medicine, biology.protein, Streptococcus gallolyticus, Antibody, business, Prospective cohort study
Abstract: The gut microbiome is increasingly implicated in colorectal cancer (CRC) development. A subgroup of patients diagnosed with CRC show high antibody responses to Streptococcus gallolyticus subspecies gallolyticus (SGG). However, it is unclear whether the association is also present pre-diagnostically. We assessed the association of antibody responses to SGG proteins in pre-diagnostic serum samples with CRC risk in a case-control study nested within a prospective cohort. Pre-diagnostic serum samples from 485 first incident CRC cases (mean time between blood draw and diagnosis 3.4 years) and 485 matched controls in the European Prospective Investigation into Nutrition and Cancer (EPIC) study were analyzed for antibody responses to 11 SGG proteins using multiplex serology. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariable conditional logistic regression models. Antibody positivity for any of the 11 SGG proteins was significantly associated with CRC risk with 56% positive controls compared to 63% positive cases (OR: 1.36, 95% CI: 1.04-1.77). Positivity for two or more proteins of a previously identified SGG 6-marker panel with greater CRC-specificity was also observed among 9% of controls compared to 17% of CRC cases, corresponding to a significantly increased CRC risk (OR: 2.17, 95% CI: 1.44-3.27). In this prospective nested case-control study, we observed a positive association between antibody responses to SGG and CRC development in serum samples taken before evident disease onset. Further work is required to establish the possibly etiological significance of these observations and whether SGG serology may be applicable for CRC risk stratification.
Published: 2018

200. Anti-hypertensive drugs and skin cancer risk: a review of the literature and meta-analysis

Author: Domenico Palli, Giuseppe Spadola, Sara Gandini, Benedetta Bendinelli, Giovanna Masala, Saverio Caini, Emilia Cocorocchio, Ignazio Stanganelli, and Lucia Miligi
Subjects: medicine.medical_specialty, Skin Neoplasms, business.industry, Hematology, Publication bias, Cochrane Library, medicine.disease, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Internal medicine, Relative risk, Meta-analysis, Epidemiology, Cutaneous melanoma, medicine, Humans, Skin cancer, business, Melanoma, Antihypertensive Agents, Thiazide, medicine.drug
Abstract: Introduction Several anti-hypertensive drugs have photosensitizing properties, however it remains unclear whether long-term users of these drugs are also at increased risk of skin malignancies. We conducted a literature review and meta-analysis on the association between use of anti-hypertensive drugs and the risk of cutaneous melanoma and non-melanoma skin cancer (NMSC). Methods We searched PubMed, EMBASE, Google Scholar and the Cochrane Library, and included observational and experimental epidemiological studies published until February 28th, 2017. We calculated summary relative risk (SRR) and 95% confidence intervals (95% CI) through random effect models to estimate the risk of skin malignancies among users of the following classes of anti-hypertensive drugs: thiazide diuretics, angiotensin converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), calcium channel blockers (CCB) and β-blockers. We conducted sub-group and sensitivity analysis to explore causes of between-studies heterogeneity, and assessed publication bias using a funnel-plot based approach. Results Nineteen independent studies were included in the meta-analysis. CCB users were at increased skin cancer risk (SRR 1.14, 95% CI 1.07–1.21), and β-blockers users were at increased risk of developing cutaneous melanoma (SRR 1.21, 95% CI 1.05–1.40), with acceptable between-studies heterogeneity (I2 Conclusion Family doctors and clinicians should inform their patients about the increased risk of skin cancer associated with the use of CCB and β-blockers and instruct them to perform periodic skin self-examination. Further studies are warranted to elucidate the observed associations.
Published: 2018

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