Author: "Wolk A." / Publisher: uppsala universitet, ortopedi - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Wolk A."' showing total 519 results

Start Over Author "Wolk A." Publisher uppsala universitet, ortopedi

519 results on '"Wolk A."'

1. Tea consumption and the risk of abdominal aortic aneurysm

Author: Kaluza, Joanna, Stackelberg, Otto, Harris, Holly R., Björck, Martin, Wolk, Alicja, Kaluza, Joanna, Stackelberg, Otto, Harris, Holly R., Björck, Martin, and Wolk, Alicja
Abstract: Background Tea has the potential to lower the risk of abdominal aortic aneurysm (AAA) owing to its high antioxidant capacity. AAA risk factors including smoking, hypertension, and hypercholesterolaemia, may modify this association. Methods The study population included 45 047 men in the Cohort of Swedish Men (COSM) and 36 611 women in the Swedish Mammography Cohort (SMC), aged 45-83 years at baseline. The COSM was established in 1997 with all men who lived in two central Swedish counties (Vastmanland and orebro), and the SMC was established in 1987-1990 with women residing in Vastmanland county. Tea consumption was assessed by means of food frequency questionnaires in 1997 and 2009. Results During 17.5 years of follow-up, 1781 AAA cases (1496 men, 285 women; 1497 non-ruptured, 284 ruptured) were ascertained via Swedish registers. Tea consumption was inversely associated with total AAA incidence in men and women. Women had a 23 (95 per cent c.i. 8 to 36) per cent lower risk of AAA per each cup per day increment, whereas men had a 9 (0 to 17) per cent lower risk (P-interaction = 0.029). Tea consumption was associated with a lower risk of both non-ruptured (hazard ratio (HR) 0.93, 95 per cent c.i. 0.85 to 1.01) and ruptured (HR 0.84, 0.71 to 0.98) AAA. Smoking status modified the association (P-interaction < 0.001), whereby tea consumption was associated with lower risk of AAA in ex-smokers (per cup per day, HR 0.89, 0.80 to 0.98) and in never smokers (HR 0.88, 0.77 to 1.00), but not in current smokers (HR 0.95, 0.84 to 1.06). Tea consumption was associated with a lower risk in participants with (HR 0.88, 0.80 to 0.98) and without (HR 0.93, 0.88 to 1.00) hypertension, and in those with (HR 0.82, 0.67 to 1.01) and without (HR 0.92, 0.86 to 0.98) hypercholesterolaemia. Conclusion Tea consumption was associated with a reduced risk of AAA. The association was more pronounced for ruptured than non-ruptured AAA, and in patients with hypertension and hypercholesterolaemia
Published: 2022
Full Text: View/download PDF

2. Interaction Analysis Based on Shapley Values and Extreme Gradient Boosting : A Realistic Simulation and Application to a Large Epidemiological Prospective Study

Author: Orsini, Nicola, Moore, Alex, Wolk, Alicja, Orsini, Nicola, Moore, Alex, and Wolk, Alicja
Abstract: BackgroundSHapley Additive exPlanations (SHAP) based on tree-based machine learning methods have been proposed to interpret interactions between exposures in observational studies, but their performance in realistic simulations is seldom evaluated. MethodsData from population-based cohorts in Sweden of 47,770 men and women with complete baseline information on diet and lifestyles were used to inform a realistic simulation in 3 scenarios of small (ORM = 0.75 vs. ORW = 0.70), moderate (ORM = 0.75 vs. ORW = 0.65), and large (ORM = 0.75 vs. ORW = 0.60) discrepancies in the adjusted mortality odds ratios conferred by a healthy diet among men and among women. Estimates were obtained with logistic regression (L-ORM; L-ORW) and derived from SHAP values (S-ORM; S-ORW). ResultsThe sensitivities of detecting small, moderate, and large discrepancies were 28, 83, and 100%, respectively. The sensitivities of a positive sign (L-ORW > L-ORM) in the 3 scenarios were 93, 100, and 100%, respectively. Similarly, the sensitivities of a positive discrepancy based on SHAP values (S-ORW > S-ORM) were 86, 99, and 100%, respectively. ConclusionsIn a realistic simulation study, the ability of the SHAP values to detect an interaction effect was proportional to its magnitude. In contrast, the ability to identify the sign or direction of such interaction effect was very high in all the simulated scenarios.
Published: 2022
Full Text: View/download PDF

3. Anti-inflammatory diet and incident peripheral artery disease : Two prospective cohort studies

Author: Yuan, Shuai, Bruzelius, Maria, Damrauer, Scott M., Hakansson, Niclas, Wolk, Alicja, Akesson, Agneta, Larsson, Susanna C., Yuan, Shuai, Bruzelius, Maria, Damrauer, Scott M., Hakansson, Niclas, Wolk, Alicja, Akesson, Agneta, and Larsson, Susanna C.
Abstract: Background & aims: Systemic inflammation plays a role in peripheral artery disease (PAD), and therefore, an anti-inflammatory diet may reduce PAD risk. We examined the association between the antiinflammatory diet and PAD risk by smoking status, a trigger of systemic inflammation. Methods: The study was based on two cohorts of 82 295 Swedish adults aged 45-83 years (38 823 women from Swedish Mammography Cohort and 45 472 men from Cohort of Swedish Men). An antiinflammatory diet index (AIDI; 0-17 scores) was used to estimate the anti-inflammatory potential of diet. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Results: Over a median 22-year (interquartile range 7.5 years) follow-up period, 3413 PAD cases were ascertained. Compared with individuals in the lowest quartile of the AIDI (score <4), the HR of PAD for those in the highest quartile (score >8) was 0.84 (95% CI, 0.74-0.94). The inverse association was observed in current and past smokers but not in never smokers. The HR of PAD comparing extreme quartiles of the AIDI was 0.67 (95% CI, 0.53-0.86) in current smoker, 0.78 (95% CI, 0.63-0.97) in past smoker, and 1.00 (95% CI, 0.82-1.23) in never smokers. Among foods included in AIDI, high consumption of breakfast cereals, chocolate, red wine, and olive/canola oil, and low consumption of processed red meat and organ meats were associated with low PAD risk. Conclusions: The study suggests that adherence to a diet with high anti-inflammatory potential may lower PAD risk, especially in smokers. (c) 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Published: 2022
Full Text: View/download PDF

4. Intake Patterns of Specific Alcoholic Beverages by Prostate Cancer Status

Author: Lin, Hui-Yi, Tseng, Tung-Sung, Wang, Xinnan, Fang, Zhide, Zea, Arnold H., Wang, Liang, Pow-Sang, Julio, Tangen, Catherine M., Goodman, Phyllis J., Wolk, Alicja, Hakansson, Niclas, Kogevinas, Manolis, Llorca, Javier, Brenner, Hermann, Schoettker, Ben, Esteban Castelao, Jose, Gago-Dominguez, Manuela, Gamulin, Marija, Lessel, Davor, Claessens, Frank, Joniau, Steven, Park, Jong Y., Lin, Hui-Yi, Tseng, Tung-Sung, Wang, Xinnan, Fang, Zhide, Zea, Arnold H., Wang, Liang, Pow-Sang, Julio, Tangen, Catherine M., Goodman, Phyllis J., Wolk, Alicja, Hakansson, Niclas, Kogevinas, Manolis, Llorca, Javier, Brenner, Hermann, Schoettker, Ben, Esteban Castelao, Jose, Gago-Dominguez, Manuela, Gamulin, Marija, Lessel, Davor, Claessens, Frank, Joniau, Steven, and Park, Jong Y.
Abstract: Simple Summary Previous studies have shown heavy intake of different alcoholic beverages affects prostate cancer (PCa) clinical outcomes differently. However, the intake patterns of specific alcoholic beverages for PCa status are understudied. The study's objective is to evaluate intake patterns of total alcohol and three types of alcoholic beverage (beer, wine, and spirits) by PCa risk and aggressiveness status. This study included 10,029 men with European ancestry (4676 non-PCa men and 5353 PCa patients). We found PCa patients had a similar total heavy alcohol intake compared with non-PCa men. However, PCa patients were likely to drink more wine and spirits than non-PCa men. Patients with aggressive PCa drank more beer but not wine and spirits. Interestingly, heavy wine intake was inversely associated with PCa aggressiveness. These findings suggest that the intake patterns of specific alcoholic beverages differ by PCa status, and this information might help develop personalized alcohol intervention for PCa patients. Background: Previous studies have shown that different alcoholic beverage types impact prostate cancer (PCa) clinical outcomes differently. However, intake patterns of specific alcoholic beverages for PCa status are understudied. The study's objective is to evaluate intake patterns of total alcohol and the three types of beverage (beer, wine, and spirits) by the PCa risk and aggressiveness status. Method: This is a cross-sectional study using 10,029 men (4676 non-PCa men and 5353 PCa patients) with European ancestry from the PCa consortium. Associations between PCa status and alcohol intake patterns (infrequent, light/moderate, and heavy) were tested using multinomial logistic regressions. Results: Intake frequency patterns of total alcohol were similar for non-PCa men and PCa patients after adjusting for demographic and other factors. However, PCa patients were more likely to drink wine (light/moderate, OR = 1.11, p = 0.018) and spirits (light/moderat
Published: 2022
Full Text: View/download PDF

5. Fruit, vegetable and dietary antioxidant intake in school age, respiratory health up to young adulthood.

Author: Sdona, Emmanouela, Ekström, Sandra, Andersson, Niklas, Hallberg, Jenny, Rautiainen, Susanne, Håkansson, Niclas, Wolk, Alicja, Kull, Inger, Melén, Erik, Bergström, Anna, Sdona, Emmanouela, Ekström, Sandra, Andersson, Niklas, Hallberg, Jenny, Rautiainen, Susanne, Håkansson, Niclas, Wolk, Alicja, Kull, Inger, Melén, Erik, and Bergström, Anna
Abstract: BACKGROUND: Dietary antioxidants may protect the lung against oxidative damage and prevent chronic respiratory disease. We aimed to investigate fruit, vegetable and antioxidant intake (measured as total antioxidant capacity, TAC) at age 8 years in relation to asthma and lung function up to 24 years. METHODS: In this study of 2506 participants from a Swedish birth cohort, diet was assessed using food frequency questionnaires. Information on asthma was collected by questionnaires, and lung function was measured by spirometry at ages 8, 16 and 24 years. Generalized estimating equations and mixed effect models were used to assess overall, age- and sex-specific associations. RESULTS: After adjustment for confounders, a higher fruit intake at age 8 years was associated with a tendency to reduced odds of prevalent asthma (T3 vs. T1, OR 0.78; 95% CI 0.60-1.01, p-trend .083), with reduced odds of incident asthma and increased odds of remittent asthma (≥median, OR 0.76; 95% CI 0.58-0.99 and OR 1.60; 95% CI 1.05-2.42, respectively) up to 24 years. Comparable, but non-significant, odds ratios were observed in analyses of long-term fruit intake (mean intake at ages 8 and 16 years). In contrast, no association was observed with vegetable intake. A higher dietary TAC (T3 vs. T1) at 8 years was associated with reduced odds of prevalent asthma (OR 0.73; 95% CI 0.58-0.93, p-trend .010) and improved lung function development (FEV1 -z +0.11; 95% CI 0.01-0.21, p-trend .036 and FVC-z +0.09; 95% CI -0.01-0.20, p-trend .072) up to 24 years. Associations were more pronounced among males, and regarding asthma, participants sensitized to aeroallergens. CONCLUSIONS: Antioxidant intake in school age may improve asthma and lung function up to young adulthood. Although our results should be interpreted with caution, they emphasize the importance of following current dietary guidelines regarding consumption of antioxidant-rich foods as part of a balanced diet.
Published: 2022
Full Text: View/download PDF

6. Long-term cadmium exposure and fractures, cardiovascular disease, and mortality in a prospective cohort of women

Author: Tagt, Jonas, Helte, Emilie, Donat-Vargas, Carolina, Larsson, Susanna C., Michaëlsson, Karl, Wolk, Alicja, Vahter, Marie, Kippler, Maria, Akesson, Agneta, Tagt, Jonas, Helte, Emilie, Donat-Vargas, Carolina, Larsson, Susanna C., Michaëlsson, Karl, Wolk, Alicja, Vahter, Marie, Kippler, Maria, and Akesson, Agneta
Abstract: Background: Cadmium (Cd) is a toxic metal, which the non-smoking population is mainly exposed to through diet. Current health-based guidance values are based on renal toxicity; however, emerging evidence suggests that bone and the cardiovascular system might be more sensitive to Cd exposure. Objective: To assess the association of urinary Cd (U-Cd) with incidence of fractures, myocardial infarction, heart failure, ischemic stroke and mortality in postmenopausal women. Methods: We used data from 4024 women, aged 56-85 in the population-based prospective Swedish Mammography Cohort-Clinical. U-Cd was measured by ICP-MS at baseline (2004-2009) and categorized into tertiles. Incident cases of the outcomes were ascertained via register linkage through 2019. Multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox regression. Results: The median U-Cd at baseline was 0.33 mu g/g creatinine (cr) (5-95 percentiles 0.15-0.77). We ascertained the following incident cases: 903 first fracture of any type, 149 myocardial infarction, 174 heart failure, 162 ischemic stroke and 545 total deaths during the approximately 11 years of follow-up. U-Cd was dose-dependently associated with risk of any fracture (HR: 1.20, 95% CI: 1.01 to 1.43, ptrend: 0.04) and all-cause mortality (HR: 1.38, 95% CI: 1.10 to 1.74, ptrend: <0.01) when comparing the highest tertile of U-Cd (median 0.54 mu g/g cr) with the lowest (median 0.20 mu g/g cr). No clear associations were observed for myocardial infarction, heart failure or stroke. Discussion: Long-term Cd exposure might be associated with risk of fractures and all-cause mortality at lower levels than previously suggested.
Published: 2022
Full Text: View/download PDF

7. Combinations of dietary calcium intake and mediterranean-style diet on risk of hip fracture : A longitudinal cohort study of 82,000 women and men

Author: Susanna C. Larsson, Liisa Byberg, Jonas Höijer, Alicja Wolk, Karl Michaëlsson, and Eva Warensjö Lemming
Subjects: 0301 basic medicine, Male, medicine.medical_specialty, Mediterranean diet, Epidemiology, Mediterranean-style diet, chemistry.chemical_element, 030209 endocrinology & metabolism, Context (language use), Calcium, Orthopaedics, Critical Care and Intensive Care Medicine, Diet, Mediterranean, Diet Surveys, Hip fracture, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Surveys and Questionnaires, medicine, Humans, Longitudinal Studies, Registries, Aged, Proportional Hazards Models, Nutrition, Sweden, 030109 nutrition & dietetics, Nutrition and Dietetics, business.industry, Hip Fractures, Hazard ratio, Middle Aged, medicine.disease, Confidence interval, Calcium, Dietary, Näringslära, chemistry, Ortopedi, Female, Diet, Healthy, business, Cohort study
Abstract: BACKGROUND AND AIMS: Each year, millions of people suffer from fragility fractures. Hip fractures are the most devastating type of such fractures. We aimed to investigate whether the association of dietary calcium intake with hip fracture risk can be modified by a healthy diet, herein defined as the modified Mediterranean diet score (mMED), in Swedish adults. METHODS: The study included 82,092 men and women at baseline. Diet and covariate data were collected twice, 12 years apart, using questionnaires. Information on incident hip fractures was collected from a national registry. Dietary calcium intake and mMED were each categorized into low, medium and high categories, and in nine combined strata of the two exposures. Multivariable adjusted hazard ratios (HR) of hip fracture with 95% confidence intervals (CI) were calculated using Cox proportional hazards regression analysis, with time-updated information on exposures and covariates. Non-linear trends were assessed using restricted cubic splines. RESULTS: During 20 years of follow-up including 1,367,260 person-years at risk, 5938 individuals experienced a hip fracture. Dietary calcium intake and hip fracture were non-linearly associated, whereas adherence to mMED decreased hip fracture rates in a dose-response pattern. The lowest hip fracture rates were observed among women and men who reported a calcium intake of 800 mg or more, combined with a high adherence to mMED. In each stratum of calcium intake, the HRs of hip fracture were increasingly higher with lower adherence to mMED, compared with the reference level (high calcium and high mMED). Individuals with low calcium intake (1200 mg/day) combined with low adherence to mMED had a HR of 1.54 (95% CI 1.28-1.85) and 1.50 (95% CI 1.26-1.77), respectively. No major differences in the hip fracture risk patterns were discerned between women and men. CONCLUSION: A moderate to high dietary calcium intake in the context of an overall healthy diet were associated with lower hip fracture rates.
Published: 2021

8. A Combined Proteomics and Mendelian Randomization Approach to Investigate the Effects of Aspirin-Targeted Proteins on Colorectal Cancer

Author: Stephanie J. Weinstein, Temitope O. Keku, Noralane M. Lindor, Dominique Scherer, Rebecca C Richmond, Graham G. Giles, Michael O. Woods, Jie Zheng, Jenny Chang-Claude, Emily White, Michael Hoffmeister, Jane C. Figueiredo, Sonja I. Berndt, Peter T. Campbell, Christopher I. Li, Steven Gallinger, D. Timothy Bishop, Andrea Gsur, Martha L. Slattery, Clemens Schafmayer, Heather Hampel, Loic Le Marchand, Lori C. Sakoda, Ludmila Vodickova, Elizabeth A. Platz, John A. Baron, Cornelia M. Ulrich, Victor Moreno, Zsofia K. Stadler, Ulrike Peters, Demetrius Albanes, Gad Rennert, Justo Lorenzo Bermejo, Hyeong Rok Kim, Alicja Wolk, Tabitha A. Harrison, Hermann Brenner, Graham Casey, Sergi Castellví-Bel, Paul D.P. Pharoah, Bethany Van Guelpen, Li Li, Wei Zheng, Stephen B. Gruber, Yi Lin, Ann C. Williams, Kate J. Heesom, Alexander Greenhough, Caroline L Relton, Pavel Vodicka, Polly A. Newcomb, Fränzel J.B. van Duijnhoven, Annika Lindblom, Anna H. Wu, Marc J. Gunter, Daniel D. Buchanan, Robert E. Schoen, Andrew T. Chan, Sun-Seog Kweon, Aayah Nounu, John L. Hopper, and David A. Drew
Subjects: 0301 basic medicine, Proteomics, Nutrition and Disease, Epidemiology, Colorectal cancer, Population, Colorectal adenoma, Biology, Article, Metastasis, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Stable isotope labeling by amino acids in cell culture, Voeding en Ziekte, Mendelian randomization, medicine, Humans, Life Science, education, 030304 developmental biology, Medicinsk genetik, 0303 health sciences, education.field_of_study, Cancer och onkologi, Cancer, Bioinformatics, Epidemiology, Aspirin, Aspirin, business.industry, Biomedical Sciences, Mendelian Randomization Analysis, medicine.disease, 3. Good health, 030104 developmental biology, Oncology, Health, 030220 oncology & carcinogenesis, Cancer and Oncology, Expression quantitative trait loci, Cancer cell, Cancer research, ICEP, Centre for Research in Biosciences, Medical Science, business, Colorectal Neoplasms, Medical Genetics
Abstract: Background: Evidence for aspirin's chemopreventative properties on colorectal cancer (CRC) is substantial, but its mechanism of action is not well-understood. We combined a proteomic approach with Mendelian randomization (MR) to identify possible new aspirin targets that decrease CRC risk. Methods: Human colorectal adenoma cells (RG/C2) were treated with aspirin (24 hours) and a stable isotope labeling with amino acids in cell culture (SILAC) based proteomics approach identified altered protein expression. Protein quantitative trait loci (pQTLs) from INTERVAL (N = 3,301) and expression QTLs (eQTLs) from the eQTLGen Consortium (N = 31,684) were used as genetic proxies for protein and mRNA expression levels. Two-sample MR of mRNA/protein expression on CRC risk was performed using eQTL/pQTL data combined with CRC genetic summary data from the Colon Cancer Family Registry (CCFR), Colorectal Transdisciplinary (CORECT), Genetics and Epidemiology of Colorectal Cancer (GECCO) consortia and UK Biobank (55,168 cases and 65,160 controls). Results: Altered expression was detected for 125/5886 proteins. Of these, aspirin decreased MCM6, RRM2, and ARFIP2 expression, and MR analysis showed that a standard deviation increase in mRNA/protein expression was associated with increased CRC risk (OR: 1.08, 95% CI, 1.03–1.13; OR: 3.33, 95% CI, 2.46–4.50; and OR: 1.15, 95% CI, 1.02–1.29, respectively). Conclusions: MCM6 and RRM2 are involved in DNA repair whereby reduced expression may lead to increased DNA aberrations and ultimately cancer cell death, whereas ARFIP2 is involved in actin cytoskeletal regulation, indicating a possible role in aspirin's reduction of metastasis. Impact: Our approach has shown how laboratory experiments and population-based approaches can combine to identify aspirin-targeted proteins possibly affecting CRC risk.
Published: 2021

9. Is the Effect of Mediterranean Diet on Hip Fracture Mediated Through Type 2 Diabetes and Body Mass Index?

Author: Alicja Wolk, Liisa Byberg, Karl Michaëlsson, Håkan Melhus, Adam Mitchell, and Tove Fall
Subjects: Male, medicine.medical_specialty, Inverse Association, Mediterranean diet, Epidemiology, type 2 diabetes mellitus, Effects of Diet, 030209 endocrinology & metabolism, body mass index, Endocrinology and Diabetes, Orthopaedics, Diet, Mediterranean, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, Type 2 diabetes mellitus, medicine, Humans, AcademicSubjects/MED00860, 030212 general & internal medicine, Body mass index, Sweden, Hip fracture, business.industry, Hip Fractures, Type 2 Diabetes Mellitus, nutritional and metabolic diseases, General Medicine, medicine.disease, Causality, Diabetes Mellitus, Type 2, Orthopedic surgery, Hip fractures, Endokrinologi och diabetes, Ortopedi, Female, business
Abstract: Background We examined whether the inverse association between adherence to a Mediterranean diet and hip fracture risk is mediated by incident type 2 diabetes mellitus (T2DM) and body mass index (BMI). Methods We included 50 755 men and women from the Cohort of Swedish Men and the Swedish Mammography Cohort who answered lifestyle and medical questionnaires in 1997 and 2008 (used for calculation of the Mediterranean diet score 9mMED; low, medium, high) and BMI in 1997, and incident T2DM in 1997–2008). The cumulative incidence of hip fracture from the National Patient Register (2009–14) was considered as outcome. Results We present conditional odds ratios (OR) 9[95% confidence interval, CI) of hip fracture for medium and high adherence to mMED, compared with low adherence. The total effect ORs were 0.82 (0.71, 0.95) and 0.75 (0.62, 0.91), respectively. The controlled direct effect of mMED on hip fracture (not mediated by T2DM, considering BMI as an exposure-induced confounder), calculated using inverse probability weighting of marginal structural models, rendered ORs of 0.82 (0.72, 0.95) and 0.73 (0.60, 0.88), respectively. The natural direct effect ORs (not mediated by BMI or T2DM, calculated using flexible mediation analysis) were 0.82 (0.71, 0.95) and 0.74(0.61, 0.89), respectively. The path-specific indirect and partial indirect natural effects ORs (through BMI or T2DM) were close to 1. Conclusions Mediterranean diet has a direct effect on hip fracture risk via pathways other than through T2DM and BMI. We cannot exclude mediating effects of T2DM or BMI, or that their effects cancel each other out.
Published: 2021

10. Circulating adipokine concentrations and risk of five obesity-related cancers : A Mendelian randomization study.

Author: Dimou, Niki L, Papadimitriou, Nikos, Mariosa, Daniela, Johansson, Mattias, Brennan, Paul, Peters, Ulrike, Chanock, Stephen J, Purdue, Mark, Bishop, D Timothy, Gago-Dominquez, Manuela, Giles, Graham G, Moreno, Victor, Platz, Elizabeth A, Tangen, Catherine M, Wolk, Alicja, Zheng, Wei, Wu, Xifeng, Campbell, Peter T, Giovannucci, Edward, Lin, Yi, Gunter, Marc J, Murphy, Neil, Dimou, Niki L, Papadimitriou, Nikos, Mariosa, Daniela, Johansson, Mattias, Brennan, Paul, Peters, Ulrike, Chanock, Stephen J, Purdue, Mark, Bishop, D Timothy, Gago-Dominquez, Manuela, Giles, Graham G, Moreno, Victor, Platz, Elizabeth A, Tangen, Catherine M, Wolk, Alicja, Zheng, Wei, Wu, Xifeng, Campbell, Peter T, Giovannucci, Edward, Lin, Yi, Gunter, Marc J, and Murphy, Neil
Abstract: Obesity is considered a chronic inflammatory state characterized by continued secretion of adipokines and cytokines. Experimental and epidemiological evidence indicates that circulating adipokines may be associated with the development of obesity-related cancers, but it is unclear if these associations are causal or confounded. We examined potential causal associations of specific adipokines (adiponectin, leptin, soluble leptin receptor [sOB-R] and plasminogen activator inhibitor-1 [PAI-1]) with five obesity-related cancers (colorectal, pancreatic, renal cell carcinoma [RCC], ovarian and endometrial) using Mendelian randomization (MR) methods. We used summary-level data from large genetic consortia for 114 530 cancer cases and 245 284 controls. We constructed genetic instruments using 18 genetic variants for adiponectin, 2 for leptin and 4 for both sOB-R and PAI-1 (P value for inclusion<5 × 10-8 ). Causal estimates were obtained using two-sample MR methods. In the inverse-variance weighted models, we found an inverse association between adiponectin and risk of colorectal cancer (odds ratio per 1 μg/mL increment in adiponectin concentration: 0.90 [95% confidence interval = 0.84-0.97]; P = .01); but, evidence of horizontal pleiotropy was detected and the association was not present when this was taken into consideration. No association was found for adiponectin and risks of pancreatic cancer, RCC, ovarian cancer and endometrial cancer. Leptin, sOB-R and PAI-1 were also similarly unrelated to risk of obesity-related cancers. Despite the large sample size, our MR analyses do not support causal effects of circulating adiponectin, leptin, sOB-R and PAI-1 concentrations on the development of five obesity-related cancers.
Published: 2021
Full Text: View/download PDF

11. Is the Effect of Mediterranean Diet on Hip Fracture Mediated Through Type 2 Diabetes and Body Mass Index?

Author: Mitchell, Adam, Fall, Tove, Melhus, Håkan, Wolk, Alicja, Michaëlsson, Karl, Byberg, Liisa, Mitchell, Adam, Fall, Tove, Melhus, Håkan, Wolk, Alicja, Michaëlsson, Karl, and Byberg, Liisa
Abstract: Background: We examined whether the inverse association between adherence to a Mediterranean diet and hip fracture risk is mediated by incident type 2 diabetes mellitus (T2DM) and body mass index (BMI). Methods: We included 50,755 men and women from the Cohort of Swedish Men and Swedish Mammography Cohort who answered lifestyle and medical questionnaires in 1997 and 2008 (used for calculation of the Mediterranean diet score [mMED; low, medium, high] and BMI in 1997, and incident T2DM in 1997-2008). The cumulative incidence of hip fracture from the National Patient Register (2009-2014) was considered as outcome. Results: We present conditional odds ratios (OR) [95% confidence interval, CI] of hip fracture for medium and high adherence to mMED, compared to low adherence. The total effect ORs were 0.82 [0.71, 0.95] and 0.75 [0.62, 0.91], respectively. The controlled direct effect of mMED on hip fracture (not mediated by T2DM, considering BMI as an exposure-induced confounder), calculated using inverse-probability weighting of marginal structural models, rendered ORs of 0.82 [0.72, 0.95] and 0.73 [0.60, 0.88], respectively. The natural direct effect ORs (not mediated by BMI or T2DM, calculated using flexible mediation analysis) were 0.82 [0.71, 0.95] and 0.74 [0.61, 0.89], respectively. The path-specific indirect and partial indirect natural effects ORs (through BMI or T2DM) were close to 1. Conclusions: Mediterranean diet has a direct effect on hip fracture risk via pathways other than through T2DM and BMI. We cannot exclude mediating effects of T2DM or BMI, or that their effects cancel each other out.
Published: 2021
Full Text: View/download PDF

12. Body size and weight change over adulthood and risk of breast cancer by menopausal and hormone receptor status : a pooled analysis of 20 prospective cohort studies

Author: van den Brandt, Piet A, Ziegler, Regina G, Wang, Molin, Hou, Tao, Li, Ruifeng, Adami, Hans-Olov, Agnoli, Claudia, Bernstein, Leslie, Buring, Julie E, Chen, Yu, Connor, Avonne E, Eliassen, A Heather, Genkinger, Jeanine M, Gierach, Gretchen, Giles, Graham G, Goodman, Gary G, Håkansson, Niclas, Krogh, Vittorio, Le Marchand, Loic, Lee, I-Min, Liao, Linda M, Martinez, M Elena, Miller, Anthony B, Milne, Roger L, Neuhouser, Marian L, Patel, Alpa V, Prizment, Anna, Robien, Kim, Rohan, Thomas E, Sawada, Norie, Schouten, Leo J, Sinha, Rashmi, Stolzenberg-Solomon, Rachael Z, Teras, Lauren R, Tsugane, Shoichiro, Visvanathan, Kala, Weiderpass, Elisabete, White, Kami K, Willett, Walter C, Wolk, Alicja, Zeleniuch-Jacquotte, Anne, Smith-Warner, Stephanie A, van den Brandt, Piet A, Ziegler, Regina G, Wang, Molin, Hou, Tao, Li, Ruifeng, Adami, Hans-Olov, Agnoli, Claudia, Bernstein, Leslie, Buring, Julie E, Chen, Yu, Connor, Avonne E, Eliassen, A Heather, Genkinger, Jeanine M, Gierach, Gretchen, Giles, Graham G, Goodman, Gary G, Håkansson, Niclas, Krogh, Vittorio, Le Marchand, Loic, Lee, I-Min, Liao, Linda M, Martinez, M Elena, Miller, Anthony B, Milne, Roger L, Neuhouser, Marian L, Patel, Alpa V, Prizment, Anna, Robien, Kim, Rohan, Thomas E, Sawada, Norie, Schouten, Leo J, Sinha, Rashmi, Stolzenberg-Solomon, Rachael Z, Teras, Lauren R, Tsugane, Shoichiro, Visvanathan, Kala, Weiderpass, Elisabete, White, Kami K, Willett, Walter C, Wolk, Alicja, Zeleniuch-Jacquotte, Anne, and Smith-Warner, Stephanie A
Abstract: Associations between anthropometric factors and breast cancer (BC) risk have varied inconsistently by estrogen and/or progesterone receptor (ER/PR) status. Associations between prediagnostic anthropometric factors and risk of premenopausal and postmenopausal BC overall and ER/PR status subtypes were investigated in a pooled analysis of 20 prospective cohorts, including 36,297 BC cases among 1,061,915 women, using multivariable Cox regression analyses, controlling for reproductive factors, diet and other risk factors. We estimated dose-response relationships and tested for nonlinear associations using restricted cubic splines. Height showed positive, linear associations for premenopausal and postmenopausal BC risk (6-7% RR increase per 5 cm increment), with stronger associations for receptor-positive subtypes. Body mass index (BMI) at cohort baseline was strongly inversely associated with premenopausal BC risk, and strongly positively-and nonlinearly-associated with postmenopausal BC (especially among women who never used hormone replacement therapy). This was primarily observed for receptor-positive subtypes. Early adult BMI (at 18-20 years) showed inverse, linear associations for premenopausal and postmenopausal BC risk (21% and 11% RR decrease per 5 kg/m2, respectively) with stronger associations for receptor-negative subtypes. Adult weight gain since 18-20 years was positively associated with postmenopausal BC risk, stronger for receptor-positive subtypes, and among women who were leaner in early adulthood. Women heavier in early adulthood generally had reduced premenopausal BC risk, independent of later weight gain. Positive associations between height, baseline (adult) BMI, adult weight gain and postmenopausal BC risk were substantially stronger for hormone receptor-positive versus negative subtypes. Premenopausal BC risk was positively associated with height, but inversely with baseline BMI and weight gain (mostly in receptor-positive subtypes). Inverse associ
Published: 2021
Full Text: View/download PDF

13. Mendelian randomisation study of smoking exposure in relation to breast cancer risk

Author: Park, Hanla A, Neumeyer, Sonja, Michailidou, Kyriaki, Bolla, Manjeet K, Wang, Qin, Dennis, Joe, Ahearn, Thomas U, Andrulis, Irene L, Anton-Culver, Hoda, Antonenkova, Natalia N, Arndt, Volker, Aronson, Kristan J, Augustinsson, Annelie, Baten, Adinda, Beane Freeman, Laura E, Becher, Heiko, Beckmann, Matthias W, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Bogdanova, Natalia V, Bojesen, Stig E, Brauch, Hiltrud, Brenner, Hermann, Brucker, Sara Y, Burwinkel, Barbara, Campa, Daniele, Canzian, Federico, Castelao, Jose E, Chanock, Stephen J, Chenevix-Trench, Georgia, Clarke, Christine L, Conroy, Don M, Couch, Fergus J, Cox, Angela, Cross, Simon S, Czene, Kamila, Daly, Mary B, Devilee, Peter, Dörk, Thilo, Dos-Santos-Silva, Isabel, Dwek, Miriam, Eccles, Diana M, Eliassen, A Heather, Engel, Christoph, Eriksson, Mikael, Evans, D Gareth, Fasching, Peter A, Flyger, Henrik, Fritschi, Lin, García-Closas, Montserrat, García-Sáenz, José A, Gaudet, Mia M, Giles, Graham G, Glendon, Gord, Goldberg, Mark S, Goldgar, David E, González-Neira, Anna, Grip, Mervi, Guénel, Pascal, Hahnen, Eric, Haiman, Christopher A, Håkansson, Niclas, Hall, Per, Hamann, Ute, Han, Sileny, Harkness, Elaine F, Hart, Steven N, He, Wei, Heemskerk-Gerritsen, Bernadette A M, Hopper, John L, Hunter, David J, Jager, Agnes, Jakubowska, Anna, John, Esther M, Jung, Audrey, Kaaks, Rudolf, Kapoor, Pooja Middha, Keeman, Renske, Khusnutdinova, Elza, Kitahara, Cari M, Koppert, Linetta B, Koutros, Stella, Kristensen, Vessela N, Kurian, Allison W, Lacey, James, Lambrechts, Diether, Le Marchand, Loic, Lo, Wing-Yee, Lubiński, Jan, Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Martinez, Maria Elena, Mavroudis, Dimitrios, Meindl, Alfons, Menon, Usha, Milne, Roger L, Muranen, Taru A, Nevanlinna, Heli, Newman, William G, Nordestgaard, Børge G, Offit, Kenneth, Olshan, Andrew F, Olsson, Håkan, Park-Simon, Tjoung-Won, Peterlongo, Paolo, Peto, Julian, Plaseska-Karanfilska, Dijana, Presneau, Nadege, Radice, Paolo, Rennert, Gad, Rennert, Hedy S, Romero, Atocha, Saloustros, Emmanouil, Sawyer, Elinor J, Schmidt, Marjanka K, Schmutzler, Rita K, Schoemaker, Minouk J, Schwentner, Lukas, Scott, Christopher, Shah, Mitul, Shu, Xiao-Ou, Simard, Jacques, Smeets, Ann, Southey, Melissa C, Spinelli, John J, Stevens, Victoria, Swerdlow, Anthony J, Tamimi, Rulla M, Tapper, William J, Taylor, Jack A, Terry, Mary Beth, Tomlinson, Ian, Troester, Melissa A, Truong, Thérèse, Vachon, Celine M, van Veen, Elke M, Vijai, Joseph, Wang, Sophia, Wendt, Camilla, Winqvist, Robert, Wolk, Alicja, Ziogas, Argyrios, Dunning, Alison M, Pharoah, Paul D P, Easton, Douglas F, Zheng, Wei, Kraft, Peter, Chang-Claude, Jenny, Park, Hanla A, Neumeyer, Sonja, Michailidou, Kyriaki, Bolla, Manjeet K, Wang, Qin, Dennis, Joe, Ahearn, Thomas U, Andrulis, Irene L, Anton-Culver, Hoda, Antonenkova, Natalia N, Arndt, Volker, Aronson, Kristan J, Augustinsson, Annelie, Baten, Adinda, Beane Freeman, Laura E, Becher, Heiko, Beckmann, Matthias W, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Bogdanova, Natalia V, Bojesen, Stig E, Brauch, Hiltrud, Brenner, Hermann, Brucker, Sara Y, Burwinkel, Barbara, Campa, Daniele, Canzian, Federico, Castelao, Jose E, Chanock, Stephen J, Chenevix-Trench, Georgia, Clarke, Christine L, Conroy, Don M, Couch, Fergus J, Cox, Angela, Cross, Simon S, Czene, Kamila, Daly, Mary B, Devilee, Peter, Dörk, Thilo, Dos-Santos-Silva, Isabel, Dwek, Miriam, Eccles, Diana M, Eliassen, A Heather, Engel, Christoph, Eriksson, Mikael, Evans, D Gareth, Fasching, Peter A, Flyger, Henrik, Fritschi, Lin, García-Closas, Montserrat, García-Sáenz, José A, Gaudet, Mia M, Giles, Graham G, Glendon, Gord, Goldberg, Mark S, Goldgar, David E, González-Neira, Anna, Grip, Mervi, Guénel, Pascal, Hahnen, Eric, Haiman, Christopher A, Håkansson, Niclas, Hall, Per, Hamann, Ute, Han, Sileny, Harkness, Elaine F, Hart, Steven N, He, Wei, Heemskerk-Gerritsen, Bernadette A M, Hopper, John L, Hunter, David J, Jager, Agnes, Jakubowska, Anna, John, Esther M, Jung, Audrey, Kaaks, Rudolf, Kapoor, Pooja Middha, Keeman, Renske, Khusnutdinova, Elza, Kitahara, Cari M, Koppert, Linetta B, Koutros, Stella, Kristensen, Vessela N, Kurian, Allison W, Lacey, James, Lambrechts, Diether, Le Marchand, Loic, Lo, Wing-Yee, Lubiński, Jan, Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Martinez, Maria Elena, Mavroudis, Dimitrios, Meindl, Alfons, Menon, Usha, Milne, Roger L, Muranen, Taru A, Nevanlinna, Heli, Newman, William G, Nordestgaard, Børge G, Offit, Kenneth, Olshan, Andrew F, Olsson, Håkan, Park-Simon, Tjoung-Won, Peterlongo, Paolo, Peto, Julian, Plaseska-Karanfilska, Dijana, Presneau, Nadege, Radice, Paolo, Rennert, Gad, Rennert, Hedy S, Romero, Atocha, Saloustros, Emmanouil, Sawyer, Elinor J, Schmidt, Marjanka K, Schmutzler, Rita K, Schoemaker, Minouk J, Schwentner, Lukas, Scott, Christopher, Shah, Mitul, Shu, Xiao-Ou, Simard, Jacques, Smeets, Ann, Southey, Melissa C, Spinelli, John J, Stevens, Victoria, Swerdlow, Anthony J, Tamimi, Rulla M, Tapper, William J, Taylor, Jack A, Terry, Mary Beth, Tomlinson, Ian, Troester, Melissa A, Truong, Thérèse, Vachon, Celine M, van Veen, Elke M, Vijai, Joseph, Wang, Sophia, Wendt, Camilla, Winqvist, Robert, Wolk, Alicja, Ziogas, Argyrios, Dunning, Alison M, Pharoah, Paul D P, Easton, Douglas F, Zheng, Wei, Kraft, Peter, and Chang-Claude, Jenny
Abstract: Background: Despite a modest association between tobacco smoking and breast cancer risk reported by recent epidemiological studies, it is still equivocal whether smoking is causally related to breast cancer risk. Methods: We applied Mendelian randomisation (MR) to evaluate a potential causal effect of cigarette smoking on breast cancer risk. Both individual-level data as well as summary statistics for 164 single-nucleotide polymorphisms (SNPs) reported in genome-wide association studies of lifetime smoking index (LSI) or cigarette per day (CPD) were used to obtain MR effect estimates. Data from 108,420 invasive breast cancer cases and 87,681 controls were used for the LSI analysis and for the CPD analysis conducted among ever-smokers from 26,147 cancer cases and 26,072 controls. Sensitivity analyses were conducted to address pleiotropy. Results: Genetically predicted LSI was associated with increased breast cancer risk (OR 1.18 per SD, 95% CI: 1.07-1.30, P = 0.11 × 10-2), but there was no evidence of association for genetically predicted CPD (OR 1.02, 95% CI: 0.78-1.19, P = 0.85). The sensitivity analyses yielded similar results and showed no strong evidence of pleiotropic effect. Conclusion: Our MR study provides supportive evidence for a potential causal association with breast cancer risk for lifetime smoking exposure but not cigarettes per day among smokers.
Published: 2021
Full Text: View/download PDF

14. Occupational physical activity is associated with risk of atrial fibrillation in both men and women : a population-based cohort study

Author: Drca, Nikola, Wolk, Alicja, Larsson, Susanna C., Drca, Nikola, Wolk, Alicja, and Larsson, Susanna C.
Abstract: Aims: Previous studies have found that excessive sport activities are associated with an increased risk of atrial fibrillation (AF). Whether occupational physical activity (OPA) increases the risk for AF is not well studied. We aimed to examine whether OPA influences the risk of AF. Methods: 80,922 men and women, free from AF, completed in 1997 a questionnaire about their OPA at that time (baseline), and also retrospectively in 1997 their OPA at the age of 30 and 50 years. Participants were categorised into three groups (low, medium and high) based on OPA load. Participants were followed-up in the Swedish National Patient Register for ascertainment of AF. Cox proportional hazards regression models were used to estimate relative risks (RR) with 95% confidence intervals (CI), adjusted for potential confounders. Results: 11,614 cases of AF were diagnosed during follow-up time of up to 17 years. We observed an increased risk of AF in relation to increased load of OPA regardless of age. Compared with men who reported a low load of OPA, the multivariable RR (95% CI) for men with a high load was 1.10 (1.03-1.17) at 30 years, 1.11 (1.04-1.17) at 50 years and 1.19 (1.10-1.29) at baseline. The results for women were similar with multivariable RR of 1.16 (1.06-1.27) at 30 years, 1.14 (1.05-1.24) at 50 years and 1.11 (0.99-1.24) at baseline. Conclusion: These findings suggest that high load of OPA previous in life may play a role in increasing the risk for AF in both men and women.
Published: 2021
Full Text: View/download PDF

15. Fracture risk across a wide range of physical activity levels, from sedentary individuals to elite athletes.

Author: Stattin, Karl, Höijer, Jonas, Hållmarker, Ulf, Baron, John A, Larsson, Susanna C., Wolk, Alicja, Michaëlsson, Karl, Byberg, Liisa, Stattin, Karl, Höijer, Jonas, Hållmarker, Ulf, Baron, John A, Larsson, Susanna C., Wolk, Alicja, Michaëlsson, Karl, and Byberg, Liisa
Abstract: OBJECTIVE: To examine how physical activity is associated with risk of different fracture outcomes across the full range of physical activity. METHODS: By combining information from three cohort studies and using generalized structural equation modelling, we estimated a continuous unitless latent variable reflecting physical activity that ranged from sedentary through elite athlete levels. Associations between physical activity and fracture outcomes were assessed with proportional hazards regression using restricted cubic splines with the mean physical activity (corresponding to 20-40 min walking or bicycling/day or 2-3 h exercise/week) as reference. RESULTS: Among 63,980 men and women (49-68 years) and during 13 years of follow-up, 8506 fractures occurred, including 2164 distal forearm, 779 proximal humerus, 346 clinical spine, and 908 hip fractures. Both lower and higher physical activity was associated with higher risk of any fracture compared to the mean. Physical activity at 1 standard deviation (SD) below the mean, corresponding to walking/bicycling <20 min/day or exercising <1-1 h/week, was associated with a lower risk of distal forearm fracture (hazard ratio [HR]: 0.92, 95% confidence interval [CI]: 0.85-0.99) and higher risk of hip fracture (HR: 1.24, 95% CI: 1.13-1.37), but no associations were seen above the mean physical activity level for these fractures. Physical activity was not associated with proximal humerus fracture but had a possible U-shaped association with clinical spine fracture. CONCLUSION: Physical activity was non-linearly associated with fracture risk and the association differed across fracture sites. Up to 2-3 h weekly exercise is beneficial for the prevention of hip fracture but may increase the risk of distal forearm fracture.
Published: 2021
Full Text: View/download PDF

16. Corrigendum to 'Measures of body fatness and height in early and mid-to-late adulthood and prostate cancer : risk and mortality in The Pooling Project of Prospective Studies of Diet and Cancer'

Author: Genkinger, J M, Wu, K, Wang, M, Albanes, D, Black, A, van den Brandt, P A, Burke, K A, Cook, M B, Gapstur, S M, Giles, G G, Giovannucci, E, Goodman, G G, Goodman, P J, Håkansson, N, Key, T J, Männistö, S, Le Marchand, L, Liao, L M, MacInnis, R J, Neuhouser, M L, Platz, E A, Sawada, N, Schenk, J M, Stevens, V L, Travis, R C, Tsugane, S, Visvanathan, K, Wilkens, L R, Wolk, Alicja, Smith-Warner, S A, Genkinger, J M, Wu, K, Wang, M, Albanes, D, Black, A, van den Brandt, P A, Burke, K A, Cook, M B, Gapstur, S M, Giles, G G, Giovannucci, E, Goodman, G G, Goodman, P J, Håkansson, N, Key, T J, Männistö, S, Le Marchand, L, Liao, L M, MacInnis, R J, Neuhouser, M L, Platz, E A, Sawada, N, Schenk, J M, Stevens, V L, Travis, R C, Tsugane, S, Visvanathan, K, Wilkens, L R, Wolk, Alicja, and Smith-Warner, S A
Abstract: Background: Advanced prostate cancer etiology is poorly understood. Few studies have examined associations ofanthropometric factors (e.g. early adulthood obesity) with advanced prostate cancer risk. Patients and methods: We carried out pooled analyses to examine associations between body fatness, height, andprostate cancer risk. Among 830 772 men, 51 734 incident prostate cancer cases were identified, including 4762advanced (T4/N1/M1 or prostate cancer deaths) cases, 2915 advanced restricted (same as advanced, but excludinglocalized cancers that resulted in death) cases, 9489 high-grade cases, and 3027 prostate cancer deaths. Coxproportional hazards models were used to calculate study-specific hazard ratios (HR) and 95% confidence intervals(CI); results were pooled using random effects models. Results: No statistically significant associations were observed for body mass index (BMI) in early adulthood for advanced,advanced restricted, and high-grade prostate cancer, and prostate cancer mortality. Positive associations were shown forBMI at baseline with advanced prostate cancer (HR ¼ 1.30, 95% CI ¼ 0.95e1.78) and prostate cancer mortality (HR ¼1.52, 95% CI ¼ 1.12e2.07) comparing BMI 35.0 kg/m2 with 21e22.9 kg/m2. When considering early adulthood andbaseline BMI together, a 27% higher prostate cancer mortality risk (95% CI ¼ 9% to 49%) was observed for men withBMI <25.0 kg/m2 in early adulthood and BMI 30.0 kg/m2 at baseline compared with BMI <25.0 kg/m2 in earlyadulthood and BMI <30.0 kg/m2 at baseline. Baseline waist circumference, comparing 110 cm with <90 cm, andwaist-to-hip ratio, comparing 1.00 with <0.90, were associated with significant 14%e16% increases in high-gradeprostate cancer risk and suggestive or significant 20%e39% increases in prostate cancer mortality risk. Height wasassociated with suggestive or significant 33%e56% risks of advanced or advanced restricted prostate cancer andprostate cancer mortality, comparing 1.90 m with <1.65 m, [Annals of Oncology Volume 31, Issue 1, January 2020, Pages 103-114]
Published: 2021
Full Text: View/download PDF

17. Combinations of dietary calcium intake and mediterranean-style diet on risk of hip fracture : A longitudinal cohort study of 82,000 women and men

Author: Warensjö Lemming, Eva, Byberg, Liisa, Höijer, Jonas, Larsson, Susanna C., Wolk, Alicja, Michaëlsson, Karl, Warensjö Lemming, Eva, Byberg, Liisa, Höijer, Jonas, Larsson, Susanna C., Wolk, Alicja, and Michaëlsson, Karl
Abstract: BACKGROUND AND AIMS: Each year, millions of people suffer from fragility fractures. Hip fractures are the most devastating type of such fractures. We aimed to investigate whether the association of dietary calcium intake with hip fracture risk can be modified by a healthy diet, herein defined as the modified Mediterranean diet score (mMED), in Swedish adults. METHODS: The study included 82,092 men and women at baseline. Diet and covariate data were collected twice, 12 years apart, using questionnaires. Information on incident hip fractures was collected from a national registry. Dietary calcium intake and mMED were each categorized into low, medium and high categories, and in nine combined strata of the two exposures. Multivariable adjusted hazard ratios (HR) of hip fracture with 95% confidence intervals (CI) were calculated using Cox proportional hazards regression analysis, with time-updated information on exposures and covariates. Non-linear trends were assessed using restricted cubic splines. RESULTS: During 20 years of follow-up including 1,367,260 person-years at risk, 5938 individuals experienced a hip fracture. Dietary calcium intake and hip fracture were non-linearly associated, whereas adherence to mMED decreased hip fracture rates in a dose-response pattern. The lowest hip fracture rates were observed among women and men who reported a calcium intake of 800 mg or more, combined with a high adherence to mMED. In each stratum of calcium intake, the HRs of hip fracture were increasingly higher with lower adherence to mMED, compared with the reference level (high calcium and high mMED). Individuals with low calcium intake (<800 mg/day) or high calcium intake (>1200 mg/day) combined with low adherence to mMED had a HR of 1.54 (95% CI 1.28-1.85) and 1.50 (95% CI 1.26-1.77), respectively. No major differences in the hip fracture risk patterns were discerned between women and men. CONCLUSION: A moderate to high dietary calcium intake in the context of an ov
Published: 2021
Full Text: View/download PDF

18. Breast Cancer Risk Factors and Survival by Tumor Subtype : Pooled Analyses from the Breast Cancer Association Consortium

Author: Morra, Anna, Jung, Audrey Y., Behrens, Sabine, Keeman, Renske, Ahearn, Thomas U., Anton-Culver, Hoda, Arndt, Volker, Augustinsson, Annelie, Auvinen, Paivi K., Freeman, Laura E. Beane, Becher, Heiko, Beckmann, Matthias W., Blomqvist, Carl, Bojesen, Stig E., Bolla, Manjeet K., Brenner, Hermann, Briceno, Ignacio, Brucker, Sara Y., Camp, Nicola J., Campa, Daniele, Canzian, Federico, Castelao, Jose E., Chanock, Stephen J., Choi, Ji-Yeob, Clarke, Christine L., Couch, Fergus J., Cox, Angela, Cross, Simon S., Czene, Kamila, Dork, Thilo, Dunning, Alison M., Dwek, Miriam, Easton, Douglas F., Eccles, Diana M., Egan, Kathleen M., Evans, D. Gareth, Fasching, Peter A., Flyger, Henrik, Gago-Dominguez, Manuela, Gapstur, Susan M., Garcia-Saenz, Jose A., Gaudet, Mia M., Giles, Graham G., Grip, Mervi, Guenel, Pascal, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Hamann, Ute, Han, Sileny N., Hart, Steven N., Hartman, Mikael, Heyworth, Jane S., Hoppe, Reiner, Hopper, John L., Hunter, David J., Ito, Hidemi, Jager, Agnes, Jakimovska, Milena, Jakubowska, Anna, Janni, Wolfgang, Kaaks, Rudolf, Kang, Daehee, Kapoor, Pooja Middha, Kitahara, Cari M., Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Lacey, James, V, Lambrechts, Diether, Le Marchand, Loic, Li, Jingmei, Lindblom, Annika, Lush, Michael, Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Mariapun, Shivaani, Matsuo, Keitaro, Mavroudis, Dimitrios, Milne, Roger L., Muranen, Taru A., Newman, William G., Noh, Dong-Young, Nordestgaard, Borge G., Obi, Nadia, Olshan, Andrew F., Olsson, Hakan, Park-Simon, Tjoung-Won, Petridis, Christos, Pharoah, Paul D. P., Plaseska-Karanfilska, Dijana, Presneau, Nadege, Rashid, Muhammad U., Rennert, Gad, Rennert, Hedy S., Rhenius, Valerie, Romero, Atocha, Saloustros, Emmanouil, Sawyer, Elinor J., Schneeweiss, Andreas, Schwentner, Lukas, Scott, Christopher, Shah, Mitul, Shen, Chen-Yang, Shu, Xiao-Ou, Southey, Melissa C., Stram, Daniel O., Tamimi, Rulla M., Tapper, William, Tollenaar, Rob A. E. M., Tomlinson, Ian, Torres, Diana, Troester, Melissa A., Truong, Therese, Vachon, Celine M., Wang, Qin, Wang, Sophia S., Williams, Justin A., Winqvist, Robert, Wolk, Alicja, Wu, Anna H., Yoo, Keun-Young, Yu, Jyh-Cherng, Zheng, Wei, Ziogas, Argyrios, Yang, Xiaohong R., Eliassen, A. Heather, Holmes, Michelle D., Garcia-Closas, Montserrat, Teo, Soo Hwang, Schmidt, Marjanka K., Chang-Claude, Jenny, Morra, Anna, Jung, Audrey Y., Behrens, Sabine, Keeman, Renske, Ahearn, Thomas U., Anton-Culver, Hoda, Arndt, Volker, Augustinsson, Annelie, Auvinen, Paivi K., Freeman, Laura E. Beane, Becher, Heiko, Beckmann, Matthias W., Blomqvist, Carl, Bojesen, Stig E., Bolla, Manjeet K., Brenner, Hermann, Briceno, Ignacio, Brucker, Sara Y., Camp, Nicola J., Campa, Daniele, Canzian, Federico, Castelao, Jose E., Chanock, Stephen J., Choi, Ji-Yeob, Clarke, Christine L., Couch, Fergus J., Cox, Angela, Cross, Simon S., Czene, Kamila, Dork, Thilo, Dunning, Alison M., Dwek, Miriam, Easton, Douglas F., Eccles, Diana M., Egan, Kathleen M., Evans, D. Gareth, Fasching, Peter A., Flyger, Henrik, Gago-Dominguez, Manuela, Gapstur, Susan M., Garcia-Saenz, Jose A., Gaudet, Mia M., Giles, Graham G., Grip, Mervi, Guenel, Pascal, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Hamann, Ute, Han, Sileny N., Hart, Steven N., Hartman, Mikael, Heyworth, Jane S., Hoppe, Reiner, Hopper, John L., Hunter, David J., Ito, Hidemi, Jager, Agnes, Jakimovska, Milena, Jakubowska, Anna, Janni, Wolfgang, Kaaks, Rudolf, Kang, Daehee, Kapoor, Pooja Middha, Kitahara, Cari M., Koutros, Stella, Kraft, Peter, Kristensen, Vessela N., Lacey, James, V, Lambrechts, Diether, Le Marchand, Loic, Li, Jingmei, Lindblom, Annika, Lush, Michael, Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Mariapun, Shivaani, Matsuo, Keitaro, Mavroudis, Dimitrios, Milne, Roger L., Muranen, Taru A., Newman, William G., Noh, Dong-Young, Nordestgaard, Borge G., Obi, Nadia, Olshan, Andrew F., Olsson, Hakan, Park-Simon, Tjoung-Won, Petridis, Christos, Pharoah, Paul D. P., Plaseska-Karanfilska, Dijana, Presneau, Nadege, Rashid, Muhammad U., Rennert, Gad, Rennert, Hedy S., Rhenius, Valerie, Romero, Atocha, Saloustros, Emmanouil, Sawyer, Elinor J., Schneeweiss, Andreas, Schwentner, Lukas, Scott, Christopher, Shah, Mitul, Shen, Chen-Yang, Shu, Xiao-Ou, Southey, Melissa C., Stram, Daniel O., Tamimi, Rulla M., Tapper, William, Tollenaar, Rob A. E. M., Tomlinson, Ian, Torres, Diana, Troester, Melissa A., Truong, Therese, Vachon, Celine M., Wang, Qin, Wang, Sophia S., Williams, Justin A., Winqvist, Robert, Wolk, Alicja, Wu, Anna H., Yoo, Keun-Young, Yu, Jyh-Cherng, Zheng, Wei, Ziogas, Argyrios, Yang, Xiaohong R., Eliassen, A. Heather, Holmes, Michelle D., Garcia-Closas, Montserrat, Teo, Soo Hwang, Schmidt, Marjanka K., and Chang-Claude, Jenny
Abstract: Background: It is not known whether modifiable lifestyle factors that predict survival after invasive breast cancer differ by subtype. Methods: We analyzed data for 121,435 women diagnosed with breast cancer from 67 studies in the Breast Cancer Association Consortium with 16,890 deaths (8,554 breast cancer specific) over 10 years. Cox regression was used to estimate associations between risk factors and 10-year all-cause mortality and breast cancer-specific mortality overall, by estrogen receptor (ER) status, and by intrinsic-like subtype. Results: There was no evidence of heterogeneous associations between risk factors and mortality by subtype (P-adj > 0.30). The strongest associations were between all-cause mortality and BMI >= 30 versus 18.5-25 kg/m(2) [HR (95% confidence interval (CI), 1.19 (1.06-1.34)]; current versus never smoking [1.37 (1.27-1.47)], high versus low physical activity [0.43 (0.21-0.86)], age >= 30 years versus < 20 years at first pregnancy [0.79 (0.72-0.86)]; >0-< 5 years versus >= 10 years since last full-term birth [1.31 (1.11-1.55)]; ever versus never use of oral contraceptives [0.91 (0.87-0.96)]; ever versus never use of menopausal hormone therapy, including current estrogen-progestin therapy [0.61 (0.54-0.69)]. Similar associations with breast cancer mortality were weaker; for example, 1.11 (1.02-1.21) for current versus never smoking. Conclusions: We confirm associations between modifiable lifestyle factors and 10-year all-cause mortality. There was no strong evidence that associations differed by ER status or intrinsic-like subtype. Impact: Given the large dataset and lack of evidence that associations between modifiable risk factors and 10-year mortality differed by subtype, these associations could be cautiously used in prognostication models to inform patient-centered care.
Published: 2021
Full Text: View/download PDF

19. Fluoride in Drinking Water, Diet, and Urine in Relation to Bone Mineral Density and Fracture Incidence in Postmenopausal Women

Author: Helte, Emilie, Donat Vargas, Carolina, Kippler, Maria, Wolk, Alicja, Michaëlsson, Karl, Åkesson, Agneta, Helte, Emilie, Donat Vargas, Carolina, Kippler, Maria, Wolk, Alicja, Michaëlsson, Karl, and Åkesson, Agneta
Abstract: Background: Although randomized controlled trials (RCTs) have demonstrated that high fluoride increases bone mineral density (BMD) and skeletal fragility, observational studies of low-dose chronic exposure through drinking water (<1.5mg/L, the maximum recommended by the World Health Organization) have been inconclusive. Objective: We assessed associations of fluoride in urine, and intake via diet and drinking water, with BMD and fracture incidence in postmenopausal women exposed to drinking water fluoride ≤1mg/L. Methods: Data were from participants in the Swedish Mammography Cohort–Clinical, a population-based prospective cohort study. At baseline (2004–2009), fluoride exposure was assessed based on urine concentrations (n=4,306) and estimated dietary intake (including drinking water) (n=4,072), and BMD was measured using dual energy X-ray absorptiometry. Incident fractures were ascertained via register-linkage through 2017. Residential history was collected to identify women with long-term consistent drinking water exposures prior to baseline. Results: At baseline, mean urine fluoride was 1.2mg/g creatinine (±1.9) and mean dietary intake was 2.2mg/d (±0.9), respectively. During follow-up, 850, 529, and 187 cases of any fractures, osteoporotic fractures, and hip fractures, respectively, were ascertained. Baseline BMD was slightly higher among women in the highest vs. lowest tertiles of exposure. Fluoride exposures were positively associated with incident hip fractures, with multivariable-adjusted hazard ratios of 1.50 (95% CI: 1.04, 2.17) and 1.59 (95% CI: 1.10, 2.30), for the highest vs. lowest tertiles of urine fluoride and dietary fluoride, respectively. Associations with other fractures were less pronounced for urine fluoride, and null for dietary fluoride. Restricting the analyses to women with consistent long-term drinking water exposures prior to baseline strengthened associations between fractures and urinary fluoride. Discussion: In this cohort of postm
Published: 2021
Full Text: View/download PDF

20. A Combined Proteomics and Mendelian Randomization Approach to Investigate the Effects of Aspirin-Targeted Proteins on Colorectal Cancer

Author: Nounu, Aayah, Greenhough, Alexander, Heesom, Kate J., Richmond, Rebecca C., Zheng, Jie, Weinstein, Stephanie J., Albanes, Demetrius, Baron, John A., Hopper, John L., Figueiredo, Jane C., Newcomb, Polly A., Lindor, Noralane M., Casey, Graham, Platz, Elizabeth A., Le Marchand, Loic, Ulrich, Cornelia M., Li, Christopher, I, van Duijnhoven, Franzel J. B., Gsur, Andrea, Campbell, Peter T., Moreno, Victor, Vodicka, Pavel, Vodickova, Ludmila, Brenner, Hermann, Chang-Claude, Jenny, Hoffmeister, Michael, Sakoda, Lori C., Slattery, Martha L., Schoen, Robert E., Gunter, Marc J., Castellvi-Bel, Sergi, Kim, Hyeong Rok, Kweon, Sun-Seog, Chan, Andrew T., Li, Li, Zheng, Wei, Bishop, D. Timothy, Buchanan, Daniel D., Giles, Graham G., Gruber, Stephen B., Rennert, Gad, Stadler, Zsofia K., Harrison, Tabitha A., Lin, Yi, Keku, Temitope O., Woods, Michael O., Schafmayer, Clemens, Van Guelpen, Bethany, Gallinger, Steven, Hampel, Heather, Berndt, Sonja, I, Pharoah, Paul D. P., Lindblom, Annika, Wolk, Alicja, Wu, Anna H., White, Emily, Peters, Ulrike, Drew, David A., Scherer, Dominique, Bermejo, Justo Lorenzo, Williams, Ann C., Relton, Caroline L., Nounu, Aayah, Greenhough, Alexander, Heesom, Kate J., Richmond, Rebecca C., Zheng, Jie, Weinstein, Stephanie J., Albanes, Demetrius, Baron, John A., Hopper, John L., Figueiredo, Jane C., Newcomb, Polly A., Lindor, Noralane M., Casey, Graham, Platz, Elizabeth A., Le Marchand, Loic, Ulrich, Cornelia M., Li, Christopher, I, van Duijnhoven, Franzel J. B., Gsur, Andrea, Campbell, Peter T., Moreno, Victor, Vodicka, Pavel, Vodickova, Ludmila, Brenner, Hermann, Chang-Claude, Jenny, Hoffmeister, Michael, Sakoda, Lori C., Slattery, Martha L., Schoen, Robert E., Gunter, Marc J., Castellvi-Bel, Sergi, Kim, Hyeong Rok, Kweon, Sun-Seog, Chan, Andrew T., Li, Li, Zheng, Wei, Bishop, D. Timothy, Buchanan, Daniel D., Giles, Graham G., Gruber, Stephen B., Rennert, Gad, Stadler, Zsofia K., Harrison, Tabitha A., Lin, Yi, Keku, Temitope O., Woods, Michael O., Schafmayer, Clemens, Van Guelpen, Bethany, Gallinger, Steven, Hampel, Heather, Berndt, Sonja, I, Pharoah, Paul D. P., Lindblom, Annika, Wolk, Alicja, Wu, Anna H., White, Emily, Peters, Ulrike, Drew, David A., Scherer, Dominique, Bermejo, Justo Lorenzo, Williams, Ann C., and Relton, Caroline L.
Abstract: Background: Evidence for aspirin's chemopreventative properties on colorectal cancer (CRC) is substantial, but its mechanism of action is not well-understood. We combined a proteomic approach with Mendelian randomization (MR) to identify possible new aspirin targets that decrease CRC risk. Methods: Human colorectal adenoma cells (RG/C2) were treated with aspirin (24 hours) and a stable isotope labeling with amino acids in cell culture (SILAC) based proteomics approach identified altered protein expression. Protein quantitative trait loci (pQTLs) from INTERVAL (N = 3,301) and expression QTLs (eQTLs) from the eQTLGen Consortium (N = 31,684) were used as genetic proxies for protein and mRNA expression levels. Two-sample MR of mRNA/protein expression on CRC risk was performed using eQTL/pQTL data combined with CRC genetic summary data from the Colon Cancer Family Registry (CCFR), Colorectal Transdisciplinary (CORECT), Genetics and Epidemiology of Colorectal Cancer (GECCO) consortia and UK Biobank (55,168 cases and 65,160 controls). Results: Altered expression was detected for 125/5886 proteins. Of these, aspirin decreased MCM6, RRM2, and ARFIP2 expression, and MR analysis showed that a standard deviation increase in mRNA/protein expression was associated with increased CRC risk (OR: 1.08, 95% CI, 1.03-1.13; OR: 3.33, 95% CI, 2.46-4.50; and OR: 1.15, 95% CI, 1.02-1.29, respectively). Conclusions: MCM6 and RRM2 are involved in DNA repair whereby reduced expression may lead to increased DNA aberrations and ultimately cancer cell death, whereas ARFIP2 is involved in actin cytoskeletal regulation, indicating a possible role in aspirin's reduction of metastasis. Impact: Our approach has shown how laboratory experiments and population-based approaches can combine to identify aspirin-targeted proteins possibly affecting CRC risk.
Published: 2021
Full Text: View/download PDF

21. Heterogeneity of Associations between Total and Types of Fish Intake and the Incidence of Type 2 Diabetes : Federated Meta-Analysis of 28 Prospective Studies Including 956,122 Participants

Author: Pastorino, Silvia, Bishop, Tom, Sharp, Stephen J., Pearce, Matthew, Akbaraly, Tasnime, Barbieri, Natalia B., Bes-Rastrollo, Maira, Beulens, Joline W. J., Chen, Zhengming, Du, Huaidong, Duncan, Bruce B., Goto, Atsushi, Härkänen, Tommi, Hashemian, Maryam, Kromhout, Daan, Järvinen, Ritva, Kivimaki, Mika, Knekt, Paul, Lin, Xu, Lund, Eiliv, Magliano, Dianna J., Malekzadeh, Reza, Martinez-Gonzalez, Miguel Ángel, O'Donoghue, Grainne, O'Gorman, Donal, Poustchi, Hossein, Rylander, Charlotta, Sawada, Norie, Shaw, Jonathan E., Schmidt, Maria, Soedamah-Muthu, Sabita S., Sun, Liang, Wen, Wanqing, Wolk, Alicja, Shu, Xiao-Ou, Zheng, Wei, Wareham, Nicholas J., Forouhi, Nita G., Pastorino, Silvia, Bishop, Tom, Sharp, Stephen J., Pearce, Matthew, Akbaraly, Tasnime, Barbieri, Natalia B., Bes-Rastrollo, Maira, Beulens, Joline W. J., Chen, Zhengming, Du, Huaidong, Duncan, Bruce B., Goto, Atsushi, Härkänen, Tommi, Hashemian, Maryam, Kromhout, Daan, Järvinen, Ritva, Kivimaki, Mika, Knekt, Paul, Lin, Xu, Lund, Eiliv, Magliano, Dianna J., Malekzadeh, Reza, Martinez-Gonzalez, Miguel Ángel, O'Donoghue, Grainne, O'Gorman, Donal, Poustchi, Hossein, Rylander, Charlotta, Sawada, Norie, Shaw, Jonathan E., Schmidt, Maria, Soedamah-Muthu, Sabita S., Sun, Liang, Wen, Wanqing, Wolk, Alicja, Shu, Xiao-Ou, Zheng, Wei, Wareham, Nicholas J., and Forouhi, Nita G.
Abstract: The association between fish consumption and new-onset type 2 diabetes is inconsistent and differs according to geographical location. We examined the association between the total and types of fish consumption and type 2 diabetes using individual participant data from 28 prospective cohort studies from the Americas (6), Europe (15), the Western Pacific (6), and the Eastern Mediterranean (1) comprising 956,122 participants and 48,084 cases of incident type 2 diabetes. Incidence rate ratios (IRRs) for associations of total fish, shellfish, fatty, lean, fried, freshwater, and saltwater fish intake and type 2 diabetes were derived for each study, adjusting for a consistent set of confounders and combined across studies using random-effects meta-analysis. We stratified all analyses by sex due to observed interaction (p = 0.002) on the association between fish and type 2 diabetes. In women, for each 100 g/week higher intake the IRRs (95% CIs) of type 2 diabetes were 1.02 (1.01–1.03, I2 = 61%) for total fish, 1.04 (1.01–1.07, I2 = 46%) for fatty fish, and 1.02 (1.00–1.04, I2 = 33%) for lean fish. In men, all associations were null. In women, we observed variation by geographical location: IRRs for total fish were 1.03 (1.02–1.04, I2 = 0%) in the Americas and null in other regions. In conclusion, we found evidence of a neutral association between total fish intake and type 2 diabetes in men, but there was a modest positive association among women with heterogeneity across studies, which was partly explained by geographical location and types of fish intake. Future research should investigate the role of cooking methods, accompanying foods and environmental pollutants, but meanwhile, existing dietary regional, national, or international guidelines should continue to guide fish consumption within overall healthy dietary patterns.
Published: 2021
Full Text: View/download PDF

22. A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Author: Coignard, Juliette, Lush, Michael, Beesley, Jonathan, O'Mara, Tracy A., Dennis, Joe, Tyrer, Jonathan P., Barnes, Daniel R., McGuffog, Lesley, Leslie, Goska, Bolla, Manjeet K., Adank, Muriel A., Agata, Simona, Ahearn, Thomas, Aittomaeki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Arnold, Norbert, Aronson, Kristan J., Arun, Banu K., Augustinsson, Annelie, Azzollini, Jacopo, Barrowdale, Daniel, Baynes, Caroline, Becher, Heko, Bermisheva, Marina, Bernstein, Leslie, Bialkowska, Katarzyna, Blomqvist, Carl, Bojesen, Stig E., Bonanni, Bernardo, Borg, Ake, Brauch, Hiltrud, Brenner, Hermann, Burwinkel, Barbara, Buys, Saundra S., Caldes, Trinidad, Caligo, Maria A., Campa, Daniele, Carter, Brian D., Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chung, Wendy K., Claes, Kathleen B. M., Clarke, Christine L., Collee, J. Margriet, Conroy, Don M., Czene, Kamila, Daly, Mary B., Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Domchek, Susan M., Dork, Thilo, dos-Santos-Silva, Isabel, Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Eliassen, A. Heather, Engel, Christoph, Eriksson, Mikael, Evans, D. Gareth, Fasching, Peter A., Flyger, Henrik, Fostira, Florentia, Friedman, Eitan, Fritschi, Lin, Frost, Debra, Gago-Dominguez, Manuela, Gapstur, Susan M., Garber, Judy, Garcia-Barberan, Vanesa, Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Gaudet, Mia M., Gayther, Simon A., Gehrig, Andrea, Georgoulias, Vassilios, Giles, Graham G., Godwin, Andrew K., Goldberg, Mark S., Goldgar, David E., Gonzalez-Neira, Anna, Greene, Mark H., Guenel, Pascal, Haeberle, Lothar, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Hamann, Ute, Harrington, Patricia A., Hart, Steven N., He, Wei, Hogervorst, Frans B. L., Hollestelle, Antoinette, Hopper, John L., Horcasitas, Darling J., Hulick, Peter J., Hunter, David J., Imyanitov, Evgeny N., Jager, Agnes, Jakubowska, Anna, James, Paul A., Jensen, Uffe Birk, John, Esther M., Jones, Michael E., Kaaks, Rudolf, Kapoor, Pooja Middha, Karlan, Beth Y., Keeman, Renske, Khusnutdinova, Elza, Kiiski, Johanna I., Ko, Yon-Dschun, Kosma, Veli-Matti, Kraft, Peter, Kurian, Allison W., Laitman, Yael, Lambrechts, Diether, Le Marchand, Loic, Lester, Jenny, Lesueur, Fabienne, Lindstrom, Tricia, Lopez-Fernandez, Adria, Loud, Jennifer T., Luccarini, Craig, Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Martens, John W. M., Mebirouk, Noura, Meindl, Alfons, Miller, Austin, Milne, Roger L., Montagna, Marco, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Nielsen, Finn C., O'Brien, Katie M., Olopade, Olufunmilayo I., Olson, Janet E., Olsson, Hakan, Osorio, Ana, Ottini, Laura, Park-Simon, Tjoung-Won, Parsons, Michael T., Pedersen, Inge Sokilde, Peshkin, Beth, Peterlongo, Paolo, Peto, Julian, Pharoah, Paul D. P., Phillips, Kelly-Anne, Polley, Eric C., Poppe, Bruce, Presneau, Nadege, Angel Pujana, Miquel, Punie, Kevin, Radice, Paolo, Rantala, Johanna, Rashid, Muhammad U., Rennert, Gad, Rennert, Hedy S., Robson, Mark, Romero, Atocha, Rossing, Maria, Saloustros, Emmanouil, Sandler, Dale P., Santella, Regina, Scheuner, Maren T., Schmidt, Marjanka K., Schmidt, Gunnar, Scott, Christopher, Sharma, Priyanka, Soucy, Penny, Southey, Melissa C., Spinelli, John J., Steinsnyder, Zoe, Stone, Jennifer, Stoppa-Lyonnet, Dominique, Swerdlow, Anthony, Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Terry, Mary Beth, Teule, Alex, Thull, Darcy L., Tischkowitz, Marc, Toland, Amanda E., Torres, Diana, Trainer, Alison H., Truong, Therese, Tung, Nadine, Vachon, Celine M., Vega, Ana, Vijai, Joseph, Wang, Qin, Wappenschmidt, Barbara, Weinberg, Clarice R., Weitzel, Jeffrey N., Wendt, Camilla, Wolk, Alicja, Yadav, Siddhartha, Yang, Xiaohong R., Yannoukakos, Drakoulis, Zheng, Wei, Ziogas, Argyrios, Zorn, Kristin K., Park, Sue K., Thomassen, Mads, Offit, Kenneth, Schmutzler, Rita K., Couch, Fergus J., Simard, Jacques, Chenevix-Trench, Georgia, Easton, Douglas F., Andrieu, Nadine, Antoniou, Antonis C., Coignard, Juliette, Lush, Michael, Beesley, Jonathan, O'Mara, Tracy A., Dennis, Joe, Tyrer, Jonathan P., Barnes, Daniel R., McGuffog, Lesley, Leslie, Goska, Bolla, Manjeet K., Adank, Muriel A., Agata, Simona, Ahearn, Thomas, Aittomaeki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Arnold, Norbert, Aronson, Kristan J., Arun, Banu K., Augustinsson, Annelie, Azzollini, Jacopo, Barrowdale, Daniel, Baynes, Caroline, Becher, Heko, Bermisheva, Marina, Bernstein, Leslie, Bialkowska, Katarzyna, Blomqvist, Carl, Bojesen, Stig E., Bonanni, Bernardo, Borg, Ake, Brauch, Hiltrud, Brenner, Hermann, Burwinkel, Barbara, Buys, Saundra S., Caldes, Trinidad, Caligo, Maria A., Campa, Daniele, Carter, Brian D., Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Chung, Wendy K., Claes, Kathleen B. M., Clarke, Christine L., Collee, J. Margriet, Conroy, Don M., Czene, Kamila, Daly, Mary B., Devilee, Peter, Diez, Orland, Ding, Yuan Chun, Domchek, Susan M., Dork, Thilo, dos-Santos-Silva, Isabel, Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Eliassen, A. Heather, Engel, Christoph, Eriksson, Mikael, Evans, D. Gareth, Fasching, Peter A., Flyger, Henrik, Fostira, Florentia, Friedman, Eitan, Fritschi, Lin, Frost, Debra, Gago-Dominguez, Manuela, Gapstur, Susan M., Garber, Judy, Garcia-Barberan, Vanesa, Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Gaudet, Mia M., Gayther, Simon A., Gehrig, Andrea, Georgoulias, Vassilios, Giles, Graham G., Godwin, Andrew K., Goldberg, Mark S., Goldgar, David E., Gonzalez-Neira, Anna, Greene, Mark H., Guenel, Pascal, Haeberle, Lothar, Hahnen, Eric, Haiman, Christopher A., Hakansson, Niclas, Hall, Per, Hamann, Ute, Harrington, Patricia A., Hart, Steven N., He, Wei, Hogervorst, Frans B. L., Hollestelle, Antoinette, Hopper, John L., Horcasitas, Darling J., Hulick, Peter J., Hunter, David J., Imyanitov, Evgeny N., Jager, Agnes, Jakubowska, Anna, James, Paul A., Jensen, Uffe Birk, John, Esther M., Jones, Michael E., Kaaks, Rudolf, Kapoor, Pooja Middha, Karlan, Beth Y., Keeman, Renske, Khusnutdinova, Elza, Kiiski, Johanna I., Ko, Yon-Dschun, Kosma, Veli-Matti, Kraft, Peter, Kurian, Allison W., Laitman, Yael, Lambrechts, Diether, Le Marchand, Loic, Lester, Jenny, Lesueur, Fabienne, Lindstrom, Tricia, Lopez-Fernandez, Adria, Loud, Jennifer T., Luccarini, Craig, Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Martens, John W. M., Mebirouk, Noura, Meindl, Alfons, Miller, Austin, Milne, Roger L., Montagna, Marco, Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Nielsen, Finn C., O'Brien, Katie M., Olopade, Olufunmilayo I., Olson, Janet E., Olsson, Hakan, Osorio, Ana, Ottini, Laura, Park-Simon, Tjoung-Won, Parsons, Michael T., Pedersen, Inge Sokilde, Peshkin, Beth, Peterlongo, Paolo, Peto, Julian, Pharoah, Paul D. P., Phillips, Kelly-Anne, Polley, Eric C., Poppe, Bruce, Presneau, Nadege, Angel Pujana, Miquel, Punie, Kevin, Radice, Paolo, Rantala, Johanna, Rashid, Muhammad U., Rennert, Gad, Rennert, Hedy S., Robson, Mark, Romero, Atocha, Rossing, Maria, Saloustros, Emmanouil, Sandler, Dale P., Santella, Regina, Scheuner, Maren T., Schmidt, Marjanka K., Schmidt, Gunnar, Scott, Christopher, Sharma, Priyanka, Soucy, Penny, Southey, Melissa C., Spinelli, John J., Steinsnyder, Zoe, Stone, Jennifer, Stoppa-Lyonnet, Dominique, Swerdlow, Anthony, Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Terry, Mary Beth, Teule, Alex, Thull, Darcy L., Tischkowitz, Marc, Toland, Amanda E., Torres, Diana, Trainer, Alison H., Truong, Therese, Tung, Nadine, Vachon, Celine M., Vega, Ana, Vijai, Joseph, Wang, Qin, Wappenschmidt, Barbara, Weinberg, Clarice R., Weitzel, Jeffrey N., Wendt, Camilla, Wolk, Alicja, Yadav, Siddhartha, Yang, Xiaohong R., Yannoukakos, Drakoulis, Zheng, Wei, Ziogas, Argyrios, Zorn, Kristin K., Park, Sue K., Thomassen, Mads, Offit, Kenneth, Schmutzler, Rita K., Couch, Fergus J., Simard, Jacques, Chenevix-Trench, Georgia, Easton, Douglas F., Andrieu, Nadine, and Antoniou, Antonis C.
Abstract: Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P<10(-8), at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers. Breast cancer risk for BRCA1/BRCA2 mutation carriers varies depending on other genetic factors. Here, the authors perform a case-only genome-wide association study and highlight novel loci associated with breast cancer risk for BRCA1/BRCA2 mutation carriers., Correction in: Nature Communications, 2021. Vol. 12, no 1, article id 2986DOI: 10.1038/s41467-021-23162-4
Published: 2021
Full Text: View/download PDF

23. Long-term dietary fiber intake and risk of chronic obstructive pulmonary disease : a prospective cohort study of women

Author: Holly R. Harris, Alicja Wolk, Anders Lindén, Maria Karolina Szmidt, and Joanna Kaluza
Subjects: 0301 basic medicine, Dietary Fiber, medicine.medical_specialty, Epidemiology, Population, Medicine (miscellaneous), 030209 endocrinology & metabolism, Lower risk, Cohort Studies, 03 medical and health sciences, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Risk Factors, Internal medicine, Vegetables, Medicine, Humans, Prospective Studies, Prospective cohort study, education, Proportional Hazards Models, Sweden, COPD, education.field_of_study, 030109 nutrition & dietetics, Nutrition and Dietetics, business.industry, Chronic obstructive pulmonary disease, Hazard ratio, Original Contribution, medicine.disease, Dietary fiber, Confidence interval, Diet, Näringslära, Fruit, Female, business, Follow-Up Studies
Abstract: Purpose Until now, only two prospective cohort studies have investigated dietary fiber intake in relation to risk of chronic obstructive pulmonary disease (COPD), but neither examined long-term fiber intake. Both studies reported that total fiber intake was associated with decreased COPD risk; however, results for specific fiber sources were inconsistent. Thus, we prospectively evaluated the association between baseline and long-term intake of dietary fiber and COPD risk in a population-based prospective cohort of 35,339 Swedish women. Methods Dietary fiber intake was assessed in 1987 and 1997 with a food frequency questionnaire. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results During follow-up (2002–2014), 1557 COPD cases were identified via linkage to the Swedish National Patient Register. Long-term high dietary fiber intake (≥ 26.5 vs.
Published: 2020

24. Genome-wide Modeling of Polygenic Risk Score in Colorectal Cancer Risk.

Author: Thomas, Minta, Sakoda, Lori C, Hoffmeister, Michael, Rosenthal, Elisabeth A, Lee, Jeffrey K, van Duijnhoven, Franzel J B, Platz, Elizabeth A, Wu, Anna H, Dampier, Christopher H, de la Chapelle, Albert, Wolk, Alicja, Joshi, Amit D, Burnett-Hartman, Andrea, Gsur, Andrea, Lindblom, Annika, Castells, Antoni, Win, Aung Ko, Namjou, Bahram, Van Guelpen, Bethany, Tangen, Catherine M, He, Qianchuan, Li, Christopher I, Schafmayer, Clemens, Joshu, Corinne E, Ulrich, Cornelia M, Bishop, D Timothy, Buchanan, Daniel D, Schaid, Daniel, Drew, David A, Muller, David C, Duggan, David, Crosslin, David R, Albanes, Demetrius, Giovannucci, Edward L, Larson, Eric, Qu, Flora, Mentch, Frank, Giles, Graham G, Hakonarson, Hakon, Hampel, Heather, Stanaway, Ian B, Figueiredo, Jane C, Huyghe, Jeroen R, Minnier, Jessica, Chang-Claude, Jenny, Hampe, Jochen, Harley, John B, Visvanathan, Kala, Curtis, Keith R, Offit, Kenneth, Li, Li, Le Marchand, Loic, Vodickova, Ludmila, Gunter, Marc J, Jenkins, Mark A, Slattery, Martha L, Lemire, Mathieu, Woods, Michael O, Song, Mingyang, Murphy, Neil, Lindor, Noralane M, Dikilitas, Ozan, Pharoah, Paul D P, Campbell, Peter T, Newcomb, Polly A, Milne, Roger L, MacInnis, Robert J, Castellví-Bel, Sergi, Ogino, Shuji, Berndt, Sonja I, Bézieau, Stéphane, Thibodeau, Stephen N, Gallinger, Steven J, Zaidi, Syed H, Harrison, Tabitha A, Keku, Temitope O, Hudson, Thomas J, Vymetalkova, Veronika, Moreno, Victor, Martín, Vicente, Arndt, Volker, Wei, Wei-Qi, Chung, Wendy, Su, Yu-Ru, Hayes, Richard B, White, Emily, Vodicka, Pavel, Casey, Graham, Gruber, Stephen B, Schoen, Robert E, Chan, Andrew T, Potter, John D, Brenner, Hermann, Jarvik, Gail P, Corley, Douglas A, Peters, Ulrike, Hsu, Li, Thomas, Minta, Sakoda, Lori C, Hoffmeister, Michael, Rosenthal, Elisabeth A, Lee, Jeffrey K, van Duijnhoven, Franzel J B, Platz, Elizabeth A, Wu, Anna H, Dampier, Christopher H, de la Chapelle, Albert, Wolk, Alicja, Joshi, Amit D, Burnett-Hartman, Andrea, Gsur, Andrea, Lindblom, Annika, Castells, Antoni, Win, Aung Ko, Namjou, Bahram, Van Guelpen, Bethany, Tangen, Catherine M, He, Qianchuan, Li, Christopher I, Schafmayer, Clemens, Joshu, Corinne E, Ulrich, Cornelia M, Bishop, D Timothy, Buchanan, Daniel D, Schaid, Daniel, Drew, David A, Muller, David C, Duggan, David, Crosslin, David R, Albanes, Demetrius, Giovannucci, Edward L, Larson, Eric, Qu, Flora, Mentch, Frank, Giles, Graham G, Hakonarson, Hakon, Hampel, Heather, Stanaway, Ian B, Figueiredo, Jane C, Huyghe, Jeroen R, Minnier, Jessica, Chang-Claude, Jenny, Hampe, Jochen, Harley, John B, Visvanathan, Kala, Curtis, Keith R, Offit, Kenneth, Li, Li, Le Marchand, Loic, Vodickova, Ludmila, Gunter, Marc J, Jenkins, Mark A, Slattery, Martha L, Lemire, Mathieu, Woods, Michael O, Song, Mingyang, Murphy, Neil, Lindor, Noralane M, Dikilitas, Ozan, Pharoah, Paul D P, Campbell, Peter T, Newcomb, Polly A, Milne, Roger L, MacInnis, Robert J, Castellví-Bel, Sergi, Ogino, Shuji, Berndt, Sonja I, Bézieau, Stéphane, Thibodeau, Stephen N, Gallinger, Steven J, Zaidi, Syed H, Harrison, Tabitha A, Keku, Temitope O, Hudson, Thomas J, Vymetalkova, Veronika, Moreno, Victor, Martín, Vicente, Arndt, Volker, Wei, Wei-Qi, Chung, Wendy, Su, Yu-Ru, Hayes, Richard B, White, Emily, Vodicka, Pavel, Casey, Graham, Gruber, Stephen B, Schoen, Robert E, Chan, Andrew T, Potter, John D, Brenner, Hermann, Jarvik, Gail P, Corley, Douglas A, Peters, Ulrike, and Hsu, Li
Abstract: Accurate colorectal cancer (CRC) risk prediction models are critical for identifying individuals at low and high risk of developing CRC, as they can then be offered targeted screening and interventions to address their risks of developing disease (if they are in a high-risk group) and avoid unnecessary screening and interventions (if they are in a low-risk group). As it is likely that thousands of genetic variants contribute to CRC risk, it is clinically important to investigate whether these genetic variants can be used jointly for CRC risk prediction. In this paper, we derived and compared different approaches to generating predictive polygenic risk scores (PRS) from genome-wide association studies (GWASs) including 55,105 CRC-affected case subjects and 65,079 control subjects of European ancestry. We built the PRS in three ways, using (1) 140 previously identified and validated CRC loci; (2) SNP selection based on linkage disequilibrium (LD) clumping followed by machine-learning approaches; and (3) LDpred, a Bayesian approach for genome-wide risk prediction. We tested the PRS in an independent cohort of 101,987 individuals with 1,699 CRC-affected case subjects. The discriminatory accuracy, calculated by the age- and sex-adjusted area under the receiver operating characteristics curve (AUC), was highest for the LDpred-derived PRS (AUC = 0.654) including nearly 1.2 M genetic variants (the proportion of causal genetic variants for CRC assumed to be 0.003), whereas the PRS of the 140 known variants identified from GWASs had the lowest AUC (AUC = 0.629). Based on the LDpred-derived PRS, we are able to identify 30% of individuals without a family history as having risk for CRC similar to those with a family history of CRC, whereas the PRS based on known GWAS variants identified only top 10% as having a similar relative risk. About 90% of these individuals have no family history and would have been considered average risk under current screening guidelines, but might be
Published: 2020
Full Text: View/download PDF

25. Associations between reproductive factors and biliary tract cancers in women from the Biliary Tract Cancers Pooling Project

Author: Jackson, Sarah S., Adami, Hans-Olov, Andreotti, Gabriella, Beane-Freeman, Laura E., de Gonzalez, Amy Berrington, Buring, Julie E., Fraser, Gary E., Freedman, Neal D., Gapstur, Susan M., Gierach, Gretchen, Giles, Graham G., Grodstein, Francine, Hartge, Patricia, Jenab, Mazda, Kirsh, Victoria, Knutsen, Synnove F., Lan, Qing, Larsson, Susanna C., Lee, I-Min, Lee, Mei-Hsuan, Liao, Linda M., Milne, Roger L., Monroe, Kristine R., Neuhouser, Marian L., O'Brien, Katie M., Petrick, Jessica L., Purdue, Mark P., Rohan, Thomas E., Sandin, Sven, Sandler, Dale P., Sawada, Norie, Shadyab, Aladdin H., Simon, Tracey G., Sinha, Rashmi, Stolzenberg-Solomon, Rachael, Tsugane, Shoichiro, Weiderpass, Elisabete, Wolk, Alicja, Yang, Hwai-, I, Zheng, Wei, McGlynn, Katherine A., Campbell, Peter T., Koshiol, Jill, Jackson, Sarah S., Adami, Hans-Olov, Andreotti, Gabriella, Beane-Freeman, Laura E., de Gonzalez, Amy Berrington, Buring, Julie E., Fraser, Gary E., Freedman, Neal D., Gapstur, Susan M., Gierach, Gretchen, Giles, Graham G., Grodstein, Francine, Hartge, Patricia, Jenab, Mazda, Kirsh, Victoria, Knutsen, Synnove F., Lan, Qing, Larsson, Susanna C., Lee, I-Min, Lee, Mei-Hsuan, Liao, Linda M., Milne, Roger L., Monroe, Kristine R., Neuhouser, Marian L., O'Brien, Katie M., Petrick, Jessica L., Purdue, Mark P., Rohan, Thomas E., Sandin, Sven, Sandler, Dale P., Sawada, Norie, Shadyab, Aladdin H., Simon, Tracey G., Sinha, Rashmi, Stolzenberg-Solomon, Rachael, Tsugane, Shoichiro, Weiderpass, Elisabete, Wolk, Alicja, Yang, Hwai-, I, Zheng, Wei, McGlynn, Katherine A., Campbell, Peter T., and Koshiol, Jill
Abstract: Background & Aims: Gallbladder cancer (GBC) is known to have a female predominance while other biliary tract cancers (BTCs) have a male predominance. However, the role of female reproductive factors in BTC etiology remains unclear. Methods: We pooled data from 19 studies of >1.5 million women participating in the Biliary Tract Cancers Pooling Project to examine the associations of parity, age at menarche, reproductive years, and age at menopause with BTC. Associations for age at menarche and reproductive years with BTC were analyzed separately for Asian and non-Asian women. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards models, stratified by study. Results: During 21,681,798 person-years of follow-up, 875 cases of GBC, 379 of intrahepatic bile duct cancer (IHBDC), 450 of extrahepatic bile duct cancer (EHBDC), and 261 of ampulla of Vater cancer (AVC) occurred. High parity was associated with risk of GBC (HR >= 5 vs. 0 births 1.72; 95% CI 1.25-2.38). Age at menarche (HR per year increase 1.15; 95% CI 1.06-1.24) was associated with GBC risk in Asian women while reproductive years were associated with GBC risk (HR per 5 years 1.13; 95% CI 1.04-1.22) in non-Asian women. Later age at menarche was associated with IHBDC (HR 1.19; 95% CI 1.09-1.31) and EHBDC (HR 1.11; 95% CI 1.01-1.22) in Asian women only. Conclusion: We observed an increased risk of GBC with increasing parity. Among Asian women, older age at menarche was associated with increased risk for GBC, IHBDC, and EHBDC, while increasing reproductive years was associated with GBC in non-Asian women. These results suggest that sex hormones have distinct effects on cancers across the biliary tract that vary by geography. Lay summary: Our findings show that the risk of gallbladder cancer is increased among women who have given birth (especially women with 5 or more children). In women from Asian countries, later age at menarche increases the risk of gallbladder cancer, intrahepat
Published: 2020
Full Text: View/download PDF

26. The CHEK2 Variant C.349A>G Is Associated with Prostate Cancer Risk and Carriers Share a Common Ancestor

Author: Brandão, Andreia, Paulo, Paula, Maia, Sofia, Pinheiro, Manuela, Peixoto, Ana, Cardoso, Marta, Silva, Maria P., Santos, Catarina, Eeles, Rosalind A., Kote-Jarai, Zsofia, Muir, Kenneth, Ukgpcs Collaborators, Schleutker, Johanna, Wang, Ying, Pashayan, Nora, Batra, Jyotsna, Apcb BioResource, Grönberg, Henrik, Neal, David E., Nordestgaard, Børge G., Tangen, Catherine M., Southey, Melissa C., Wolk, Alicja, Albanes, Demetrius, Haiman, Christopher A., Travis, Ruth C., Stanford, Janet L., Mucci, Lorelei A., West, Catharine M. L., Nielsen, Sune F., Kibel, Adam S., Cussenot, Olivier, Berndt, Sonja I., Koutros, Stella, Dalsgaard Sørensen, Karina, Cybulski, Cezary, Grindedal, Eli Marie, Park, Jong Y., Ingles, Sue A., Maier, Christiane, Hamilton, Robert J., Rosenstein, Barry S., Vega, Ana, The Impact Study Steering Committee And Collaborators, Kogevinas, Manolis, Wiklund, Fredrik, Penney, Kathryn L., Brenner, Hermann, John, Esther M., Kaneva, Radka, Logothetis, Christopher J., Neuhausen, Susan L., De Ruyck, Kim, Razack, Azad, Newcomb, Lisa F., Canary PASS Investigators, Lessel, Davor, Usmani, Nawaid, Claessens, Frank, Gago-Dominguez, Manuela, Townsend, Paul A., Roobol, Monique J., The Profile Study Steering Committee, The PRACTICAL Consortium, Teixeira, Manuel R., Brandão, Andreia, Paulo, Paula, Maia, Sofia, Pinheiro, Manuela, Peixoto, Ana, Cardoso, Marta, Silva, Maria P., Santos, Catarina, Eeles, Rosalind A., Kote-Jarai, Zsofia, Muir, Kenneth, Ukgpcs Collaborators, Schleutker, Johanna, Wang, Ying, Pashayan, Nora, Batra, Jyotsna, Apcb BioResource, Grönberg, Henrik, Neal, David E., Nordestgaard, Børge G., Tangen, Catherine M., Southey, Melissa C., Wolk, Alicja, Albanes, Demetrius, Haiman, Christopher A., Travis, Ruth C., Stanford, Janet L., Mucci, Lorelei A., West, Catharine M. L., Nielsen, Sune F., Kibel, Adam S., Cussenot, Olivier, Berndt, Sonja I., Koutros, Stella, Dalsgaard Sørensen, Karina, Cybulski, Cezary, Grindedal, Eli Marie, Park, Jong Y., Ingles, Sue A., Maier, Christiane, Hamilton, Robert J., Rosenstein, Barry S., Vega, Ana, The Impact Study Steering Committee And Collaborators, Kogevinas, Manolis, Wiklund, Fredrik, Penney, Kathryn L., Brenner, Hermann, John, Esther M., Kaneva, Radka, Logothetis, Christopher J., Neuhausen, Susan L., De Ruyck, Kim, Razack, Azad, Newcomb, Lisa F., Canary PASS Investigators, Lessel, Davor, Usmani, Nawaid, Claessens, Frank, Gago-Dominguez, Manuela, Townsend, Paul A., Roobol, Monique J., The Profile Study Steering Committee, The PRACTICAL Consortium, and Teixeira, Manuel R.
Abstract: The identification of recurrent founder variants in cancer predisposing genes may have important implications for implementing cost-effective targeted genetic screening strategies. In this study, we evaluated the prevalence and relative risk of the CHEK2 recurrent variant c.349A>G in a series of 462 Portuguese patients with early-onset and/or familial/hereditary prostate cancer (PrCa), as well as in the large multicentre PRACTICAL case-control study comprising 55,162 prostate cancer cases and 36,147 controls. Additionally, we investigated the potential shared ancestry of the carriers by performing identity-by-descent, haplotype and age estimation analyses using high-density SNP data from 70 variant carriers belonging to 11 different populations included in the PRACTICAL consortium. The CHEK2 missense variant c.349A>G was found significantly associated with an increased risk for PrCa (OR 1.9; 95% CI: 1.1-3.2). A shared haplotype flanking the variant in all carriers was identified, strongly suggesting a common founder of European origin. Additionally, using two independent statistical algorithms, implemented by DMLE+2.3 and ESTIAGE, we were able to estimate the age of the variant between 2300 and 3125 years. By extending the haplotype analysis to 14 additional carrier families, a shared core haplotype was revealed among all carriers matching the conserved region previously identified in the high-density SNP analysis. These findings are consistent with CHEK2 c.349A>G being a founder variant associated with increased PrCa risk, suggesting its potential usefulness for cost-effective targeted genetic screening in PrCa families.
Published: 2020
Full Text: View/download PDF

27. Combined associations of body mass index and adherence to a Mediterranean-like diet with all-cause and cardiovascular mortality : A cohort study

Author: Michaëlsson, Karl, Baron, John A., Byberg, Liisa, Höijer, Jonas, Larsson, Susanna C., Svennblad, Bodil, Melhus, Håkan, Wolk, Alicja, Warensjö Lemming, Eva, Michaëlsson, Karl, Baron, John A., Byberg, Liisa, Höijer, Jonas, Larsson, Susanna C., Svennblad, Bodil, Melhus, Håkan, Wolk, Alicja, and Warensjö Lemming, Eva
Abstract: Background It is unclear whether the effect on mortality of a higher body mass index (BMI) can be compensated for by adherence to a healthy diet and whether the effect on mortality by a low adherence to a healthy diet can be compensated for by a normal weight. We aimed to evaluate the associations of BMI combined with adherence to a Mediterranean-like diet on all-cause and cardiovascular disease (CVD) mortality. Methods and findings Our longitudinal cohort design included the Swedish Mammography Cohort (SMC) and the Cohort of Swedish Men (COSM) (1997–2017), with a total of 79,003 women (44%) and men (56%) and a mean baseline age of 61 years. BMI was categorized into normal weight (20–24.9 kg/m2), overweight (25–29.9 kg/m2), and obesity (30+ kg/m2). Adherence to a Mediterranean-like diet was assessed by means of the modified Mediterranean-like diet (mMED) score, ranging from 0 to 8; mMED was classified into 3 categories (0 to <4, 4 to <6, and 6–8 score points), forming a total of 9 BMI × mMED combinations. We identified mortality by use of national Swedish registers. Cox proportional hazard models with time-updated information on exposure and covariates were used to calculate the adjusted hazard ratios (HRs) of mortality with their 95% confidence intervals (CIs). Our HRs were adjusted for age, baseline educational level, marital status, leisure time physical exercise, walking/cycling, height, energy intake, smoking habits, baseline Charlson’s weighted comorbidity index, and baseline diabetes mellitus. During up to 21 years of follow-up, 30,389 (38%) participants died, corresponding to 22 deaths per 1,000 person-years. We found the lowest HR of all-cause mortality among overweight individuals with high mMED (HR 0.94; 95% CI 0.90, 0.98) compared with those with normal weight and high mMED. Using the same reference, obese individuals with high mMED did not experience significantly higher all-cause mortality (HR 1.03; 95% CI 0.96–1.11). In contrast, compared with t
Published: 2020
Full Text: View/download PDF

28. Long-term consumption of non-fermented and fermented dairy products and risk of breast cancer by estrogen receptor status - Population-based prospective cohort study.

Author: Kaluza, Joanna, Komatsu, Shoko, Lauriola, Mara, Harris, Holly R, Bergkvist, Leif, Michaëlsson, Karl, Wolk, Alicja, Kaluza, Joanna, Komatsu, Shoko, Lauriola, Mara, Harris, Holly R, Bergkvist, Leif, Michaëlsson, Karl, and Wolk, Alicja
Abstract: BACKGROUND & AIMS: The impact of dairy consumption on breast cancer development is unclear. We sought to examine associations between long-term consumption of milk and fermented dairy products and risk of breast cancer by estrogen (ER) and progesterone receptor (PR) status and assess whether these associations varied by body weight. METHODS: The population-based Swedish Mammography Cohort included 33,780 women (88.2% postmenopausal), with no history of cancer or diabetes at baseline (1997). Long-term consumption of dairy products was assessed using a self-administered food-frequency questionnaire in 1987 and 1997. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During 16.6 years of follow-up (559,286 person-years), 1870 total breast cancer cases were diagnosed (1162 ER+/PR+; 195 ER-/PR-). High long-term non-fermented milk consumption was associated with increased ER+/PR+ breast cancer incidence, HR = 1.30, 95%CI:1.02-1.65 for the average of 1987 and 1997 intake ≥2 vs. 0 servings/day and this increased risk was limited to women with BMI<25 kg/m2 HR = 1.55, 95%CI:1.08-2.21, while no significant associations with milk consumption were observed with ER-/PR- breast cancer. In contrast, consumption of fermented dairy products was inversely associated with ER-/PR- breast cancer (for consistently high intake ≥3 vs. <1 servings/day HR = 0.28, 95%CI:0.10-0.78), but not clear association was observed for ER+/PR+ (HR = 0.89, 95%CI:0.69-1.14). CONCLUSIONS: In this cohort of mainly postmenopausal women, high long-term consumption of milk was associated with increased risk of ER+/PR+ breast cancer. In contrast, high long-term consumption of fermented dairy products was associated with decreased risk of ER-/PR- breast cancer.
Published: 2020
Full Text: View/download PDF

29. Functional informed genome-wide interaction analysis of body mass index, diabetes and colorectal cancer risk.

Author: Xia, Zhiyu, Su, Yu-Ru, Petersen, Paneen, Qi, Lihong, Kim, Andre E, Figueiredo, Jane C, Lin, Yi, Nan, Hongmei, Sakoda, Lori C, Albanes, Demetrius, Berndt, Sonja I, Bézieau, Stéphane, Bien, Stephanie, Buchanan, Daniel D, Casey, Graham, Chan, Andrew T, Conti, David V, Drew, David A, Gallinger, Steven J, Gauderman, W James, Giles, Graham G, Gruber, Stephen B, Gunter, Marc J, Hoffmeister, Michael, Jenkins, Mark A, Joshi, Amit D, Le Marchand, Loic, Lewinger, Juan P, Li, Li, Lindor, Noralane M, Moreno, Victor, Murphy, Neil, Nassir, Rami, Newcomb, Polly A, Ogino, Shuji, Rennert, Gad, Song, Mingyang, Wang, Xiaoliang, Wolk, Alicja, Woods, Michael O, Brenner, Hermann, White, Emily, Slattery, Martha L, Giovannucci, Edward L, Chang-Claude, Jenny, Pharoah, Paul D P, Hsu, Li, Campbell, Peter T, Peters, Ulrike, Xia, Zhiyu, Su, Yu-Ru, Petersen, Paneen, Qi, Lihong, Kim, Andre E, Figueiredo, Jane C, Lin, Yi, Nan, Hongmei, Sakoda, Lori C, Albanes, Demetrius, Berndt, Sonja I, Bézieau, Stéphane, Bien, Stephanie, Buchanan, Daniel D, Casey, Graham, Chan, Andrew T, Conti, David V, Drew, David A, Gallinger, Steven J, Gauderman, W James, Giles, Graham G, Gruber, Stephen B, Gunter, Marc J, Hoffmeister, Michael, Jenkins, Mark A, Joshi, Amit D, Le Marchand, Loic, Lewinger, Juan P, Li, Li, Lindor, Noralane M, Moreno, Victor, Murphy, Neil, Nassir, Rami, Newcomb, Polly A, Ogino, Shuji, Rennert, Gad, Song, Mingyang, Wang, Xiaoliang, Wolk, Alicja, Woods, Michael O, Brenner, Hermann, White, Emily, Slattery, Martha L, Giovannucci, Edward L, Chang-Claude, Jenny, Pharoah, Paul D P, Hsu, Li, Campbell, Peter T, and Peters, Ulrike
Abstract: BACKGROUND: Body mass index (BMI) and diabetes are established risk factors for colorectal cancer (CRC), likely through perturbations in metabolic traits (e.g. insulin resistance and glucose homeostasis). Identification of interactions between variation in genes and these metabolic risk factors may identify novel biologic insights into CRC etiology. METHODS: To improve statistical power and interpretation for gene-environment interaction (G × E) testing, we tested genetic variants that regulate expression of a gene together for interaction with BMI (kg/m2 ) and diabetes on CRC risk among 26 017 cases and 20 692 controls. Each variant was weighted based on PrediXcan analysis of gene expression data from colon tissue generated in the Genotype-Tissue Expression Project for all genes with heritability ≥1%. We used a mixed-effects model to jointly measure the G × E interaction in a gene by partitioning the interactions into the predicted gene expression levels (fixed effects), and residual G × E effects (random effects). G × BMI analyses were stratified by sex as BMI-CRC associations differ by sex. We used false discovery rates to account for multiple comparisons and reported all results with FDR <0.2. RESULTS: Among 4839 genes tested, genetically predicted expressions of FOXA1 (P = 3.15 × 10-5 ), PSMC5 (P = 4.51 × 10-4 ) and CD33 (P = 2.71 × 10-4 ) modified the association of BMI on CRC risk for men; KIAA0753 (P = 2.29 × 10-5 ) and SCN1B (P = 2.76 × 10-4 ) modified the association of BMI on CRC risk for women; and PTPN2 modified the association between diabetes and CRC risk in both sexes (P = 2.31 × 10-5 ). CONCLUSIONS: Aggregating G × E interactions and incorporating functional information, we discovered novel genes that may interact with BMI and diabetes on CRC risk.
Published: 2020
Full Text: View/download PDF

30. Physical activity and risks of breast and colorectal cancer : a Mendelian randomisation analysis.

Author: Papadimitriou, Nikos, Dimou, Niki, Tsilidis, Konstantinos K, Banbury, Barbara, Martin, Richard M, Lewis, Sarah J, Kazmi, Nabila, Robinson, Timothy M, Albanes, Demetrius, Aleksandrova, Krasimira, Berndt, Sonja I, Timothy Bishop, D, Brenner, Hermann, Buchanan, Daniel D, Bueno-de-Mesquita, Bas, Campbell, Peter T, Castellví-Bel, Sergi, Chan, Andrew T, Chang-Claude, Jenny, Ellingjord-Dale, Merete, Figueiredo, Jane C, Gallinger, Steven J, Giles, Graham G, Giovannucci, Edward, Gruber, Stephen B, Gsur, Andrea, Hampe, Jochen, Hampel, Heather, Harlid, Sophia, Harrison, Tabitha A, Hoffmeister, Michael, Hopper, John L, Hsu, Li, María Huerta, José, Huyghe, Jeroen R, Jenkins, Mark A, Keku, Temitope O, Kühn, Tilman, La Vecchia, Carlo, Le Marchand, Loic, Li, Christopher I, Li, Li, Lindblom, Annika, Lindor, Noralane M, Lynch, Brigid, Markowitz, Sanford D, Masala, Giovanna, May, Anne M, Milne, Roger, Monninkhof, Evelyn, Moreno, Lorena, Moreno, Victor, Newcomb, Polly A, Offit, Kenneth, Perduca, Vittorio, Pharoah, Paul D P, Platz, Elizabeth A, Potter, John D, Rennert, Gad, Riboli, Elio, Sánchez, Maria-Jose, Schmit, Stephanie L, Schoen, Robert E, Severi, Gianluca, Sieri, Sabina, Slattery, Martha L, Song, Mingyang, Tangen, Catherine M, Thibodeau, Stephen N, Travis, Ruth C, Trichopoulou, Antonia, Ulrich, Cornelia M, van Duijnhoven, Franzel J B, Van Guelpen, Bethany, Vodicka, Pavel, White, Emily, Wolk, Alicja, Woods, Michael O, Wu, Anna H, Peters, Ulrike, Gunter, Marc J, Murphy, Neil, Papadimitriou, Nikos, Dimou, Niki, Tsilidis, Konstantinos K, Banbury, Barbara, Martin, Richard M, Lewis, Sarah J, Kazmi, Nabila, Robinson, Timothy M, Albanes, Demetrius, Aleksandrova, Krasimira, Berndt, Sonja I, Timothy Bishop, D, Brenner, Hermann, Buchanan, Daniel D, Bueno-de-Mesquita, Bas, Campbell, Peter T, Castellví-Bel, Sergi, Chan, Andrew T, Chang-Claude, Jenny, Ellingjord-Dale, Merete, Figueiredo, Jane C, Gallinger, Steven J, Giles, Graham G, Giovannucci, Edward, Gruber, Stephen B, Gsur, Andrea, Hampe, Jochen, Hampel, Heather, Harlid, Sophia, Harrison, Tabitha A, Hoffmeister, Michael, Hopper, John L, Hsu, Li, María Huerta, José, Huyghe, Jeroen R, Jenkins, Mark A, Keku, Temitope O, Kühn, Tilman, La Vecchia, Carlo, Le Marchand, Loic, Li, Christopher I, Li, Li, Lindblom, Annika, Lindor, Noralane M, Lynch, Brigid, Markowitz, Sanford D, Masala, Giovanna, May, Anne M, Milne, Roger, Monninkhof, Evelyn, Moreno, Lorena, Moreno, Victor, Newcomb, Polly A, Offit, Kenneth, Perduca, Vittorio, Pharoah, Paul D P, Platz, Elizabeth A, Potter, John D, Rennert, Gad, Riboli, Elio, Sánchez, Maria-Jose, Schmit, Stephanie L, Schoen, Robert E, Severi, Gianluca, Sieri, Sabina, Slattery, Martha L, Song, Mingyang, Tangen, Catherine M, Thibodeau, Stephen N, Travis, Ruth C, Trichopoulou, Antonia, Ulrich, Cornelia M, van Duijnhoven, Franzel J B, Van Guelpen, Bethany, Vodicka, Pavel, White, Emily, Wolk, Alicja, Woods, Michael O, Wu, Anna H, Peters, Ulrike, Gunter, Marc J, and Murphy, Neil
Abstract: Physical activity has been associated with lower risks of breast and colorectal cancer in epidemiological studies; however, it is unknown if these associations are causal or confounded. In two-sample Mendelian randomisation analyses, using summary genetic data from the UK Biobank and GWA consortia, we found that a one standard deviation increment in average acceleration was associated with lower risks of breast cancer (odds ratio [OR]: 0.51, 95% confidence interval [CI]: 0.27 to 0.98, P-value = 0.04) and colorectal cancer (OR: 0.66, 95% CI: 0.48 to 0.90, P-value = 0.01). We found similar magnitude inverse associations for estrogen positive (ER+ve) breast cancer and for colon cancer. Our results support a potentially causal relationship between higher physical activity levels and lower risks of breast cancer and colorectal cancer. Based on these data, the promotion of physical activity is probably an effective strategy in the primary prevention of these commonly diagnosed cancers.
Published: 2020
Full Text: View/download PDF

31. Genotypes of HLA, TCF7L2, and FTO as potential modifiers of the association between sweetened beverage consumption and risk of LADA and type 2 diabetes.

Author: Löfvenborg, Josefin E, Ahlqvist, Emma, Alfredsson, Lars, Andersson, Tomas, Dorkhan, Mozhgan, Groop, Leif, Tuomi, Tiinamaija, Wolk, Alicja, Carlsson, Sofia, Löfvenborg, Josefin E, Ahlqvist, Emma, Alfredsson, Lars, Andersson, Tomas, Dorkhan, Mozhgan, Groop, Leif, Tuomi, Tiinamaija, Wolk, Alicja, and Carlsson, Sofia
Abstract: PURPOSE: Sweetened beverage consumption is associated with type 2 diabetes (T2D) and LADA. We investigated to what extent this association is mediated by BMI and whether it is modified by genotypes of HLA, TCF7L2 rs7903146, or FTO rs9939609. METHODS: Swedish case-control data including incident cases of LADA (n = 386) and T2D (n = 1253) with matched population-based controls (n = 1545) was used. We estimated adjusted ORs of diabetes (95% CI) in relation to sweetened beverage intake (per daily 200 mL serving) and genotypes. The impact of BMI was estimated using causal mediation methodology. Associations with HOMA-IR and HOMA-B were explored through linear regression. RESULTS: Sweetened beverage intake was associated with increased risk of LADA (OR 1.15, 95% CI 1.03-1.29) and T2D (OR 1.21, 1.11-1.32). BMI was estimated to mediate 17% (LADA) and 56% (T2D) of the total risk. LADA was associated with risk variants of HLA (3.44, 2.63-4.50) and TCF7L2 (1.27, 1.00-1.61) but not FTO. Only among non-carriers of high-risk HLA genotypes was sweetened beverage intake associated with risk of LADA (OR 1.32, 1.06-1.56) and HOMA-IR (beta = 0.162, p = 0.0047). T2D was associated with TCF7L2 and FTO but not HLA, and the risk conferred by sweetened beverages appeared modified by FTO (OR 1.45, 95% CI 1.21-1.73 in non-carriers). CONCLUSIONS: Our findings suggest that sweetened beverages are associated with LADA and T2D partly through mediation by excess weight, but possibly also through other mechanisms including adverse effects on insulin sensitivity. These effects seem more pronounced in individuals without genetic susceptibility.
Published: 2020
Full Text: View/download PDF

32. Mendelian Randomization of Circulating Polyunsaturated Fatty Acids and Colorectal Cancer Risk.

Author: Khankari, Nikhil K, Banbury, Barbara L, Borges, Maria C, Haycock, Philip, Albanes, Demetrius, Arndt, Volker, Berndt, Sonja I, Bézieau, Stéphane, Brenner, Hermann, Campbell, Peter T, Casey, Graham, Chan, Andrew T, Chang-Claude, Jenny, Conti, David V, Cotterchio, Michelle, English, Dallas R, Figueiredo, Jane C, Giles, Graham G, Giovannucci, Edward L, Gunter, Marc J, Hampe, Jochen, Hoffmeister, Michael, Hopper, John L, Jenkins, Mark A, Joshi, Amit D, Marchand, Loic Le, Lemire, Mathieu, Li, Christopher I, Li, Li, Lindblom, Annika, Martín, Vicente, Moreno, Victor, Newcomb, Polly A, Offit, Kenneth, Pharoah, Paul D P, Rennert, Gad, Sakoda, Lori C, Schafmayer, Clemens, Schmit, Stephanie L, Slattery, Martha L, Song, Mingyang, Thibodeau, Stephen N, Ulrich, Cornelia M, Weinstein, Stephanie J, White, Emily, Win, Aung Ko, Wolk, Alicja, Woods, Michael O, Wu, Anna H, Cai, Qiuyin, Denny, Joshua C, Edwards, Todd L, Murff, Harvey J, Gruber, Stephen B, Peters, Ulrike, Zheng, Wei, Khankari, Nikhil K, Banbury, Barbara L, Borges, Maria C, Haycock, Philip, Albanes, Demetrius, Arndt, Volker, Berndt, Sonja I, Bézieau, Stéphane, Brenner, Hermann, Campbell, Peter T, Casey, Graham, Chan, Andrew T, Chang-Claude, Jenny, Conti, David V, Cotterchio, Michelle, English, Dallas R, Figueiredo, Jane C, Giles, Graham G, Giovannucci, Edward L, Gunter, Marc J, Hampe, Jochen, Hoffmeister, Michael, Hopper, John L, Jenkins, Mark A, Joshi, Amit D, Marchand, Loic Le, Lemire, Mathieu, Li, Christopher I, Li, Li, Lindblom, Annika, Martín, Vicente, Moreno, Victor, Newcomb, Polly A, Offit, Kenneth, Pharoah, Paul D P, Rennert, Gad, Sakoda, Lori C, Schafmayer, Clemens, Schmit, Stephanie L, Slattery, Martha L, Song, Mingyang, Thibodeau, Stephen N, Ulrich, Cornelia M, Weinstein, Stephanie J, White, Emily, Win, Aung Ko, Wolk, Alicja, Woods, Michael O, Wu, Anna H, Cai, Qiuyin, Denny, Joshua C, Edwards, Todd L, Murff, Harvey J, Gruber, Stephen B, Peters, Ulrike, and Zheng, Wei
Abstract: BACKGROUND: Results from epidemiologic studies examining polyunsaturated fatty acids (PUFA) and colorectal cancer risk are inconsistent. Mendelian randomization may strengthen causal inference from observational studies. Given their shared metabolic pathway, examining the combined effects of aspirin/NSAID use with PUFAs could help elucidate an association between PUFAs and colorectal cancer risk. METHODS: Information was leveraged from genome-wide association studies (GWAS) regarding PUFA-associated SNPs to create weighted genetic scores (wGS) representing genetically predicted circulating blood PUFAs for 11,016 non-Hispanic white colorectal cancer cases and 13,732 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Associations per SD increase in the wGS were estimated using unconditional logistic regression. Interactions between PUFA wGSs and aspirin/NSAID use on colorectal cancer risk were also examined. RESULTS: Modest colorectal cancer risk reductions were observed per SD increase in circulating linoleic acid [ORLA = 0.96; 95% confidence interval (CI) = 0.93-0.98; P = 5.2 × 10-4] and α-linolenic acid (ORALA = 0.95; 95% CI = 0.92-0.97; P = 5.4 × 10-5), whereas modest increased risks were observed for arachidonic (ORAA = 1.06; 95% CI = 1.03-1.08; P = 3.3 × 10-5), eicosapentaenoic (OREPA = 1.04; 95% CI = 1.01-1.07; P = 2.5 × 10-3), and docosapentaenoic acids (ORDPA = 1.03; 95% CI = 1.01-1.06; P = 1.2 × 10-2). Each of these effects was stronger among aspirin/NSAID nonusers in the stratified analyses. CONCLUSIONS: Our study suggests that higher circulating shorter-chain PUFAs (i.e., LA and ALA) were associated with reduced colorectal cancer risk, whereas longer-chain PUFAs (i.e., AA, EPA, and DPA) were associated with an increased colorectal cancer risk. IMPACT: The interaction of PUFAs with aspirin/NSAID use indicates a shared colorectal cancer inflammatory pathway. Future research should continue to improve PUFA genetic instruments t
Published: 2020
Full Text: View/download PDF

33. Identification of Novel Loci and New Risk Variant in Known Loci for Colorectal Cancer Risk in East Asians.

Author: Lu, Yingchang, Kweon, Sun-Seog, Cai, Qiuyin, Tanikawa, Chizu, Shu, Xiao-Ou, Jia, Wei-Hua, Xiang, Yong-Bing, Huyghe, Jeroen R, Harrison, Tabitha A, Kim, Jeongseon, Shin, Aesun, Kim, Dong-Hyun, Matsuo, Keitaro, Jee, Sun Ha, Guo, Xingyi, Wen, Wanqing, Shi, Jiajun, Li, Bingshan, Wang, Nan, Shin, Min-Ho, Li, Hong-Lan, Ren, Zefang, Oh, Jae Hwan, Oze, Isao, Ahn, Yoon-Ok, Jung, Keum Ji, Gao, Jing, Gao, Yu-Tang, Pan, Zhi-Zhong, Kamatani, Yoichiro, Chan, Andrew T, Gsur, Andrea, Hampe, Jochen, Le Marchand, Loic, Li, Li, Lindblom, Annika, Moreno, Victor, Newcomb, Polly A, Offit, Kenneth, Pharoah, Paul D P, van Duijnhoven, Franzel J B, Van Guelpen, Bethany, Vodicka, Pavel, Weinstein, Stephanie J, Wolk, Alicja, Wu, Anna H, Hsu, Li, Zeng, Yi-Xin, Long, Jirong, Peters, Ulrike, Matsuda, Koichi, Zheng, Wei, Lu, Yingchang, Kweon, Sun-Seog, Cai, Qiuyin, Tanikawa, Chizu, Shu, Xiao-Ou, Jia, Wei-Hua, Xiang, Yong-Bing, Huyghe, Jeroen R, Harrison, Tabitha A, Kim, Jeongseon, Shin, Aesun, Kim, Dong-Hyun, Matsuo, Keitaro, Jee, Sun Ha, Guo, Xingyi, Wen, Wanqing, Shi, Jiajun, Li, Bingshan, Wang, Nan, Shin, Min-Ho, Li, Hong-Lan, Ren, Zefang, Oh, Jae Hwan, Oze, Isao, Ahn, Yoon-Ok, Jung, Keum Ji, Gao, Jing, Gao, Yu-Tang, Pan, Zhi-Zhong, Kamatani, Yoichiro, Chan, Andrew T, Gsur, Andrea, Hampe, Jochen, Le Marchand, Loic, Li, Li, Lindblom, Annika, Moreno, Victor, Newcomb, Polly A, Offit, Kenneth, Pharoah, Paul D P, van Duijnhoven, Franzel J B, Van Guelpen, Bethany, Vodicka, Pavel, Weinstein, Stephanie J, Wolk, Alicja, Wu, Anna H, Hsu, Li, Zeng, Yi-Xin, Long, Jirong, Peters, Ulrike, Matsuda, Koichi, and Zheng, Wei
Abstract: BACKGROUND: Risk variants identified so far for colorectal cancer explain only a small proportion of familial risk of this cancer, particularly in Asians. METHODS: We performed a genome-wide association study (GWAS) of colorectal cancer in East Asians, including 23,572 colorectal cancer cases and 48,700 controls. To identify novel risk loci, we selected 60 promising risk variants for replication using data from 58,131 colorectal cancer cases and 67,347 controls of European descent. To identify additional risk variants in known colorectal cancer loci, we performed conditional analyses in East Asians. RESULTS: An indel variant, rs67052019 at 1p13.3, was found to be associated with colorectal cancer risk at P = 3.9 × 10-8 in Asians (OR per allele deletion = 1.13, 95% confidence interval = 1.08-1.18). This association was replicated in European descendants using a variant (rs2938616) in complete linkage disequilibrium with rs67052019 (P = 7.7 × 10-3). Of the remaining 59 variants, 12 showed an association at P < 0.05 in the European-ancestry study, including rs11108175 and rs9634162 at P < 5 × 10-8 and two variants with an association near the genome-wide significance level (rs60911071, P = 5.8 × 10-8; rs62558833, P = 7.5 × 10-8) in the combined analyses of Asian- and European-ancestry data. In addition, using data from East Asians, we identified 13 new risk variants at 11 loci reported from previous GWAS. CONCLUSIONS: In this large GWAS, we identified three novel risk loci and two highly suggestive loci for colorectal cancer risk and provided evidence for potential roles of multiple genes and pathways in the etiology of colorectal cancer. In addition, we showed that additional risk variants exist in many colorectal cancer risk loci identified previously. IMPACT: Our study provides novel data to improve the understanding of the genetic basis for colorectal cancer risk.
Published: 2020
Full Text: View/download PDF

34. Fruits and vegetables intake and gastric cancer risk : A pooled analysis within the Stomach cancer Pooling Project.

Author: Ferro, Ana, Costa, Ana Rute, Morais, Samantha, Bertuccio, Paola, Rota, Matteo, Pelucchi, Claudio, Hu, Jinfu, Johnson, Kenneth C, Zhang, Zuo-Feng, Palli, Domenico, Ferraroni, Monica, Yu, Guo-Pei, Bonzi, Rossella, Peleteiro, Bárbara, López-Carrillo, Lizbeth, Tsugane, Shoichiro, Hamada, Gerson Shigueaki, Hidaka, Akihisa, Malekzadeh, Reza, Zaridze, David, Maximovich, Dmitry, Vioque, Jesus, Navarrete-Muñoz, Eva M, Alguacil, Juan, Castaño-Vinyals, Gemma, Wolk, Alicja, Håkansson, Niclas, Hernández-Ramírez, Raúl Ulises, Pakseresht, Mohammadreza, Ward, Mary H, Pourfarzi, Farhad, Mu, Lina, López-Cervantes, Malaquias, Persiani, Roberto, Kurtz, Robert C, Lagiou, Areti, Lagiou, Pagona, Boffetta, Paolo, Boccia, Stefania, Negri, Eva, Camargo, Maria Constanza, Curado, Maria Paula, La Vecchia, Carlo, Lunet, Nuno, Ferro, Ana, Costa, Ana Rute, Morais, Samantha, Bertuccio, Paola, Rota, Matteo, Pelucchi, Claudio, Hu, Jinfu, Johnson, Kenneth C, Zhang, Zuo-Feng, Palli, Domenico, Ferraroni, Monica, Yu, Guo-Pei, Bonzi, Rossella, Peleteiro, Bárbara, López-Carrillo, Lizbeth, Tsugane, Shoichiro, Hamada, Gerson Shigueaki, Hidaka, Akihisa, Malekzadeh, Reza, Zaridze, David, Maximovich, Dmitry, Vioque, Jesus, Navarrete-Muñoz, Eva M, Alguacil, Juan, Castaño-Vinyals, Gemma, Wolk, Alicja, Håkansson, Niclas, Hernández-Ramírez, Raúl Ulises, Pakseresht, Mohammadreza, Ward, Mary H, Pourfarzi, Farhad, Mu, Lina, López-Cervantes, Malaquias, Persiani, Roberto, Kurtz, Robert C, Lagiou, Areti, Lagiou, Pagona, Boffetta, Paolo, Boccia, Stefania, Negri, Eva, Camargo, Maria Constanza, Curado, Maria Paula, La Vecchia, Carlo, and Lunet, Nuno
Abstract: A low intake of fruits and vegetables is a risk factor for gastric cancer, although there is uncertainty regarding the magnitude of the associations. In our study, the relationship between fruits and vegetables intake and gastric cancer was assessed, complementing a previous work on the association betweenconsumption of citrus fruits and gastric cancer. Data from 25 studies (8456 cases and 21 133 controls) with information on fruits and/or vegetables intake were used. A two-stage approach based on random-effects models was used to pool study-specific adjusted (sex, age and the main known risk factors for gastric cancer) odds ratios (ORs) and the corresponding 95% confidence intervals (CIs). Exposure-response relations, including linear and nonlinear associations, were modeled using one- and two-order fractional polynomials. Gastric cancer risk was lower for a higher intake of fruits (OR: 0.76, 95% CI: 0.64-0.90), noncitrus fruits (OR: 0.86, 95% CI: 0.73-1.02), vegetables (OR: 0.68, 95% CI: 0.56-0.84), and fruits and vegetables (OR: 0.61, 95% CI: 0.49-0.75); results were consistent across sociodemographic and lifestyles categories, as well as study characteristics. Exposure-response analyses showed an increasingly protective effect of portions/day of fruits (OR: 0.64, 95% CI: 0.57-0.73 for six portions), noncitrus fruits (OR: 0.71, 95% CI: 0.61-0.83 for six portions) and vegetables (OR: 0.51, 95% CI: 0.43-0.60 for 10 portions). A protective effect of all fruits, noncitrus fruits and vegetables was confirmed, supporting further dietary recommendations to decrease the burden of gastric cancer.
Published: 2020
Full Text: View/download PDF

35. Occupational physical activity is associated with risk of atrial fibrillation in both men and women : a population-based cohort study.

Author: Drca, Nikola, Wolk, Alicja, Larsson, Susanna C, Drca, Nikola, Wolk, Alicja, and Larsson, Susanna C
Abstract: Aims: Previous studies have found that excessive sport activities are associated with an increased risk of atrial fibrillation (AF). Whether occupational physical activity (OPA) increases the risk for AF is not well studied. We aimed to examine whether OPA influences the risk of AF.Methods: 80,922 men and women, free from AF, completed in 1997 a questionnaire about their OPA at that time (baseline), and also retrospectively in 1997 their OPA at the age of 30 and 50 years. Participants were categorised into three groups (low, medium and high) based on OPA load. Participants were followed-up in the Swedish National Patient Register for ascertainment of AF. Cox proportional hazards regression models were used to estimate relative risks (RR) with 95% confidence intervals (CI), adjusted for potential confounders.Results: 11,614 cases of AF were diagnosed during follow-up time of up to 17 years. We observed an increased risk of AF in relation to increased load of OPA regardless of age. Compared with men who reported a low load of OPA, the multivariable RR (95% CI) for men with a high load was 1.10 (1.03-1.17) at 30 years, 1.11 (1.04-1.17) at 50 years and 1.19 (1.10-1.29) at baseline. The results for women were similar with multivariable RR of 1.16 (1.06-1.27) at 30 years, 1.14 (1.05-1.24) at 50 years and 1.11 (0.99-1.24) at baseline.Conclusion: These findings suggest that high load of OPA previous in life may play a role in increasing the risk for AF in both men and women.
Published: 2020
Full Text: View/download PDF

36. Adherence to a Mediterranean diet is associated with a lower risk of later-onset Crohn's disease : results from two large prospective cohort studies.

Author: Khalili, Hamed, Håkansson, Niclas, Chan, Simon S, Chen, Ye, Lochhead, Paul, Ludvigsson, Jonas F, Chan, Andrew T, Hart, Andrew R, Olén, Ola, Wolk, Alicja, Khalili, Hamed, Håkansson, Niclas, Chan, Simon S, Chen, Ye, Lochhead, Paul, Ludvigsson, Jonas F, Chan, Andrew T, Hart, Andrew R, Olén, Ola, and Wolk, Alicja
Abstract: OBJECTIVE: To examine the relationship between Mediterranean diet and risk of later-onset Crohn's disease (CD) or ulcerative colitis (UC). DESIGN: We conducted a prospective cohort study of 83 147 participants (age range: 45-79 years) enrolled in the Cohort of Swedish Men and Swedish Mammography Cohort. A validated food frequency questionnaire was used to calculate an adherence score to a modified Mediterranean diet (mMED) at baseline in 1997. Incident diagnoses of CD and UC were ascertained from the Swedish Patient Register. We used Cox proportional hazards modelling to calculate HRs and 95% CI. RESULTS: Through December of 2017, we confirmed 164 incident cases of CD and 395 incident cases of UC with an average follow-up of 17 years. Higher mMED score was associated with a lower risk of CD (Ptrend=0.03) but not UC (Ptrend=0.61). Compared with participants in the lowest category of mMED score (0-2), there was a statistically significant lower risk of CD (HR=0.42, 95% CI 0.22 to 0.80) but not UC (HR=1.08, 95% CI 0.74 to 1.58). These associations were not modified by age, sex, education level, body mass index or smoking (all Pinteraction >0.30). The prevalence of poor adherence to a Mediterranean diet (mMED score=0-2) was 27% in our cohorts, conferring a population attributable risk of 12% for later-onset CD. CONCLUSION: In two prospective studies, greater adherence to a Mediterranean diet was associated with a significantly lower risk of later-onset CD.
Published: 2020
Full Text: View/download PDF

37. Consumption of red meat, genetic susceptibility, and risk of LADA and type 2 diabetes.

Author: Löfvenborg, Josefin E, Ahlqvist, Emma, Alfredsson, Lars, Andersson, Tomas, Groop, Leif, Tuomi, Tiinamaija, Wolk, Alicja, Carlsson, Sofia, Löfvenborg, Josefin E, Ahlqvist, Emma, Alfredsson, Lars, Andersson, Tomas, Groop, Leif, Tuomi, Tiinamaija, Wolk, Alicja, and Carlsson, Sofia
Abstract: PURPOSE: Red meat consumption is positively associated with type 1 (T1D) and type 2 (T2D) diabetes. We investigated if red meat consumption increases the risk of latent autoimmune diabetes in adults (LADA) and T2D, and potential interaction with family history of diabetes (FHD), HLA and TCF7L2 genotypes. METHODS: Analyses were based on Swedish case-control data comprising incident cases of LADA (n = 465) and T2D (n = 1528) with matched, population-based controls (n = 1789; n = 1553 in genetic analyses). Multivariable-adjusted ORs in relation to self-reported processed and unprocessed red meat intake were estimated by conditional logistic regression models. Attributable proportion (AP) due to interaction was used to assess departure from additivity of effects. RESULTS: Consumption of processed red meat was associated with increased risk of LADA (per one servings/day OR 1.27, 95% CI 1.07-1.52), whereas no association was observed for unprocessed red meat. For T2D, there was no association with red meat intake once BMI was taken into account. The combination of high (> 0.3 servings/day vs. less) processed red meat intake and high-risk HLA-DQB1 and -DRB1 genotypes yielded OR 8.05 (95% CI 4.86-13.34) for LADA, with indications of significant interaction (AP 0.53, 95% CI 0.32-0.73). Results were similar for the combination of FHD-T1D and processed red meat. No interaction between processed red meat intake and FHD-T2D or risk variants of TCF7L2 was seen in relation to LADA or T2D. CONCLUSION: Consumption of processed but not unprocessed red meat may increase the risk of LADA, especially in individuals with FHD-T1D or high-risk HLA genotypes.
Published: 2020
Full Text: View/download PDF

38. Circulating bilirubin levels and risk of colorectal cancer : serological and Mendelian randomization analyses.

Author: Seyed Khoei, Nazlisadat, Jenab, Mazda, Murphy, Neil, Banbury, Barbara L, Carreras-Torres, Robert, Viallon, Vivian, Kühn, Tilman, Bueno-de-Mesquita, Bas, Aleksandrova, Krasimira, Cross, Amanda J, Weiderpass, Elisabete, Stepien, Magdalena, Bulmer, Andrew, Tjønneland, Anne, Boutron-Ruault, Marie-Christine, Severi, Gianluca, Carbonnel, Franck, Katzke, Verena, Boeing, Heiner, Bergmann, Manuela M, Trichopoulou, Antonia, Karakatsani, Anna, Martimianaki, Georgia, Palli, Domenico, Tagliabue, Giovanna, Panico, Salvatore, Tumino, Rosario, Sacerdote, Carlotta, Skeie, Guri, Merino, Susana, Bonet, Catalina, Rodríguez-Barranco, Miguel, Gil, Leire, Chirlaque, Maria-Dolores, Ardanaz, Eva, Myte, Robin, Hultdin, Johan, Perez-Cornago, Aurora, Aune, Dagfinn, Tsilidis, Konstantinos K, Albanes, Demetrius, Baron, John A, Berndt, Sonja I, Bézieau, Stéphane, Brenner, Hermann, Campbell, Peter T, Casey, Graham, Chan, Andrew T, Chang-Claude, Jenny, Chanock, Stephen J, Cotterchio, Michelle, Gallinger, Steven, Gruber, Stephen B, Haile, Robert W, Hampe, Jochen, Hoffmeister, Michael, Hopper, John L, Hsu, Li, Huyghe, Jeroen R, Jenkins, Mark A, Joshi, Amit D, Kampman, Ellen, Larsson, Susanna C, Le Marchand, Loic, Li, Christopher I, Li, Li, Lindblom, Annika, Lindor, Noralane M, Martín, Vicente, Moreno, Victor, Newcomb, Polly A, Offit, Kenneth, Ogino, Shuji, Parfrey, Patrick S, Pharoah, Paul D P, Rennert, Gad, Sakoda, Lori C, Schafmayer, Clemens, Schmit, Stephanie L, Schoen, Robert E, Slattery, Martha L, Thibodeau, Stephen N, Ulrich, Cornelia M, van Duijnhoven, Franzel J B, Weigl, Korbinian, Weinstein, Stephanie J, White, Emily, Wolk, Alicja, Woods, Michael O, Wu, Anna H, Zhang, Xuehong, Ferrari, Pietro, Anton, Gabriele, Peters, Annette, Peters, Ulrike, Gunter, Marc J, Wagner, Karl-Heinz, Freisling, Heinz, Seyed Khoei, Nazlisadat, Jenab, Mazda, Murphy, Neil, Banbury, Barbara L, Carreras-Torres, Robert, Viallon, Vivian, Kühn, Tilman, Bueno-de-Mesquita, Bas, Aleksandrova, Krasimira, Cross, Amanda J, Weiderpass, Elisabete, Stepien, Magdalena, Bulmer, Andrew, Tjønneland, Anne, Boutron-Ruault, Marie-Christine, Severi, Gianluca, Carbonnel, Franck, Katzke, Verena, Boeing, Heiner, Bergmann, Manuela M, Trichopoulou, Antonia, Karakatsani, Anna, Martimianaki, Georgia, Palli, Domenico, Tagliabue, Giovanna, Panico, Salvatore, Tumino, Rosario, Sacerdote, Carlotta, Skeie, Guri, Merino, Susana, Bonet, Catalina, Rodríguez-Barranco, Miguel, Gil, Leire, Chirlaque, Maria-Dolores, Ardanaz, Eva, Myte, Robin, Hultdin, Johan, Perez-Cornago, Aurora, Aune, Dagfinn, Tsilidis, Konstantinos K, Albanes, Demetrius, Baron, John A, Berndt, Sonja I, Bézieau, Stéphane, Brenner, Hermann, Campbell, Peter T, Casey, Graham, Chan, Andrew T, Chang-Claude, Jenny, Chanock, Stephen J, Cotterchio, Michelle, Gallinger, Steven, Gruber, Stephen B, Haile, Robert W, Hampe, Jochen, Hoffmeister, Michael, Hopper, John L, Hsu, Li, Huyghe, Jeroen R, Jenkins, Mark A, Joshi, Amit D, Kampman, Ellen, Larsson, Susanna C, Le Marchand, Loic, Li, Christopher I, Li, Li, Lindblom, Annika, Lindor, Noralane M, Martín, Vicente, Moreno, Victor, Newcomb, Polly A, Offit, Kenneth, Ogino, Shuji, Parfrey, Patrick S, Pharoah, Paul D P, Rennert, Gad, Sakoda, Lori C, Schafmayer, Clemens, Schmit, Stephanie L, Schoen, Robert E, Slattery, Martha L, Thibodeau, Stephen N, Ulrich, Cornelia M, van Duijnhoven, Franzel J B, Weigl, Korbinian, Weinstein, Stephanie J, White, Emily, Wolk, Alicja, Woods, Michael O, Wu, Anna H, Zhang, Xuehong, Ferrari, Pietro, Anton, Gabriele, Peters, Annette, Peters, Ulrike, Gunter, Marc J, Wagner, Karl-Heinz, and Freisling, Heinz
Abstract: BACKGROUND: Bilirubin, a byproduct of hemoglobin breakdown and purported anti-oxidant, is thought to be cancer preventive. We conducted complementary serological and Mendelian randomization (MR) analyses to investigate whether alterations in circulating levels of bilirubin are associated with risk of colorectal cancer (CRC). We decided a priori to perform analyses separately in men and women based on suggestive evidence that associations may differ by sex. METHODS: In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC), pre-diagnostic unconjugated bilirubin (UCB, the main component of total bilirubin) concentrations were measured by high-performance liquid chromatography in plasma samples of 1386 CRC cases and their individually matched controls. Additionally, 115 single-nucleotide polymorphisms (SNPs) robustly associated (P < 5 × 10-8) with circulating total bilirubin were instrumented in a 2-sample MR to test for a potential causal effect of bilirubin on CRC risk in 52,775 CRC cases and 45,940 matched controls in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colon Cancer Family Registry (CCFR), and the Colorectal Transdisciplinary (CORECT) study. RESULTS: The associations between circulating UCB levels and CRC risk differed by sex (Pheterogeneity = 0.008). Among men, higher levels of UCB were positively associated with CRC risk (odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.04-1.36; per 1-SD increment of log-UCB). In women, an inverse association was observed (OR = 0.86 (0.76-0.97)). In the MR analysis of the main UGT1A1 SNP (rs6431625), genetically predicted higher levels of total bilirubin were associated with a 7% increase in CRC risk in men (OR = 1.07 (1.02-1.12); P = 0.006; per 1-SD increment of total bilirubin), while there was no association in women (OR = 1.01 (0.96-1.06); P = 0.73). Raised bilirubin levels, predicted by instrumental variables excluding rs6431625
Published: 2020
Full Text: View/download PDF

39. Circulating Levels of Insulin-like Growth Factor 1 and Insulin-like Growth Factor Binding Protein 3 Associate With Risk of Colorectal Cancer Based on Serologic and Mendelian Randomization Analyses

Author: Murphy, Neil, Carreras-Torres, Robert, Song, Mingyang, Chan, Andrew T., Martin, Richard M., Papadimitriou, Nikos, Dimou, Niki, Tsilidis, Konstantinos K., Banbury, Barbara, Bradbury, Kathryn E., Besevic, Jelena, Rinaldi, Sabina, Riboli, Elio, Cross, Amanda J., Travis, Ruth C., Agnoli, Claudia, Albanes, Demetrius, Berndt, Sonja I., Bezieau, Stephane, Bishop, D. Timothy, Brenner, Hermann, Buchanan, Daniel D., Onland-Moret, N. Charlotte, Burnett-Hartman, Andrea, Campbell, Peter T., Casey, Graham, Castellvi-Bel, Sergi, Chang-Claude, Jenny, Chirlaque, Maria-Dolores, de la Chapelle, Albert, English, Dallas, Figueiredo, Jane C., Gallinger, Steven J., Giles, Graham G., Gruber, Stephen B., Gsur, Andrea, Hampe, Jochen, Hampel, Heather, Harrison, Tabitha A., Hoffmeister, Michael, Hsu, Li, Huang, Wen-Yi, Huyghe, Jeroen R., Jenkins, Mark A., Keku, Temitope O., Kuhn, Tilman, Kweon, Sun-Seog, Le Marchand, Loic, Li, Christopher I., Li, Li, Lindblom, Annika, Martin, Vicente, Milne, Roger L., Moreno, Victor, Newcomb, Polly A., Offit, Kenneth, Ogino, Shuji, Ose, Jennifer, Perduca, Vittorio, Phipps, Amanda I., Platz, Elizabeth A., Potter, John D., Qu, Conghui, Rennert, Gad, Sakoda, Lori C., Schafmayer, Clemens, Schoen, Robert E., Slattery, Martha L., Tangen, Catherine M., Ulrich, Cornelia M., van Duijnhoven, Franzel J. B., Van Guelpen, Bethany, Visvanathan, Kala, Vodicka, Pavel, Vodickova, Ludmila, Vymetalkova, Veronika, Wang, Hansong, White, Emily, Wolk, Alicja, Woods, Michael O., Wu, Anna H., Zheng, Wei, Peters, Ulrike, Gunter, Marc J., Murphy, Neil, Carreras-Torres, Robert, Song, Mingyang, Chan, Andrew T., Martin, Richard M., Papadimitriou, Nikos, Dimou, Niki, Tsilidis, Konstantinos K., Banbury, Barbara, Bradbury, Kathryn E., Besevic, Jelena, Rinaldi, Sabina, Riboli, Elio, Cross, Amanda J., Travis, Ruth C., Agnoli, Claudia, Albanes, Demetrius, Berndt, Sonja I., Bezieau, Stephane, Bishop, D. Timothy, Brenner, Hermann, Buchanan, Daniel D., Onland-Moret, N. Charlotte, Burnett-Hartman, Andrea, Campbell, Peter T., Casey, Graham, Castellvi-Bel, Sergi, Chang-Claude, Jenny, Chirlaque, Maria-Dolores, de la Chapelle, Albert, English, Dallas, Figueiredo, Jane C., Gallinger, Steven J., Giles, Graham G., Gruber, Stephen B., Gsur, Andrea, Hampe, Jochen, Hampel, Heather, Harrison, Tabitha A., Hoffmeister, Michael, Hsu, Li, Huang, Wen-Yi, Huyghe, Jeroen R., Jenkins, Mark A., Keku, Temitope O., Kuhn, Tilman, Kweon, Sun-Seog, Le Marchand, Loic, Li, Christopher I., Li, Li, Lindblom, Annika, Martin, Vicente, Milne, Roger L., Moreno, Victor, Newcomb, Polly A., Offit, Kenneth, Ogino, Shuji, Ose, Jennifer, Perduca, Vittorio, Phipps, Amanda I., Platz, Elizabeth A., Potter, John D., Qu, Conghui, Rennert, Gad, Sakoda, Lori C., Schafmayer, Clemens, Schoen, Robert E., Slattery, Martha L., Tangen, Catherine M., Ulrich, Cornelia M., van Duijnhoven, Franzel J. B., Van Guelpen, Bethany, Visvanathan, Kala, Vodicka, Pavel, Vodickova, Ludmila, Vymetalkova, Veronika, Wang, Hansong, White, Emily, Wolk, Alicja, Woods, Michael O., Wu, Anna H., Zheng, Wei, Peters, Ulrike, and Gunter, Marc J.
Abstract: BACKGROUND & AIMS: Human studies examining associations between circulating levels of insulin-like growth factor 1 (IGF1) and insulin-like growth factor binding protein 3 (IGFBP3) and colorectal cancer risk have reported inconsistent results. We conducted complementary serologic and Mendelian randomization (MR) analyses to determine whether alterations in circulating levels of IGF1 or IGFBP3 are associated with colorectal cancer development. METHODS: Serum levels of IGF1 were measured in blood samples collected from 397,380 participants from the UK Biobank, from 2006 through 2010. Incident cancer cases and cancer cases recorded first in death certificates were identified through linkage to national cancer and death registries. Complete follow-up was available through March 31, 2016. For the MR analyses, we identified genetic variants associated with circulating levels of IGF1 and IGFBP3. The association of these genetic variants with colorectal cancer was examined with 2-sample MR methods using genomewide association study consortia data (52,865 cases with colorectal cancer and 46,287 individuals without [controls]) RESULTS: After a median follow-up period of 7.1 years, 2665 cases of colorectal cancer were recorded. In a multivariableadjusted model, circulating level of IGF1 associated with colorectal cancer risk (hazard ratio per 1 standard deviation increment of IGF1, 1.11; 95% confidence interval [CI] 1.051.17). Similar associations were found by sex, follow-up time, and tumor subsite. In the MR analyses, a 1 standard deviation increment in IGF1 level, predicted based on genetic factors, was associated with a higher risk of colorectal cancer risk (odds ratio 1.08; 95% CI 1.03-1.12; P = 3.3 x 10(-4)). Level of IGFBP3, predicted based on genetic factors, was associated with colorectal cancer risk (odds ratio per 1 standard deviation increment, 1.12; 95% CI 1.06-1.18; P = 4.2 x 10(-5)). Colorectal cancer risk was associated with only 1 variant in the IGFBP3 gene
Published: 2020
Full Text: View/download PDF

40. A data mining approach to investigate food groups related to incidence of bladder cancer in the BLadder cancer Epidemiology and Nutritional Determinants International Study.

Author: Yu, Evan Y W, Wesselius, Anke, Sinhart, Christoph, Wolk, Alicja, Stern, Mariana Carla, Jiang, Xuejuan, Tang, Li, Marshall, James, Kellen, Eliane, van den Brandt, Piet, Lu, Chih-Ming, Pohlabeln, Hermann, Steineck, Gunnar, Allam, Mohamed Farouk, Karagas, Margaret R, La Vecchia, Carlo, Porru, Stefano, Carta, Angela, Golka, Klaus, Johnson, Kenneth C, Benhamou, Simone, Zhang, Zuo-Feng, Bosetti, Cristina, Taylor, Jack A, Weiderpass, Elisabete, Grant, Eric J, White, Emily, Polesel, Jerry, Zeegers, Maurice P A, Yu, Evan Y W, Wesselius, Anke, Sinhart, Christoph, Wolk, Alicja, Stern, Mariana Carla, Jiang, Xuejuan, Tang, Li, Marshall, James, Kellen, Eliane, van den Brandt, Piet, Lu, Chih-Ming, Pohlabeln, Hermann, Steineck, Gunnar, Allam, Mohamed Farouk, Karagas, Margaret R, La Vecchia, Carlo, Porru, Stefano, Carta, Angela, Golka, Klaus, Johnson, Kenneth C, Benhamou, Simone, Zhang, Zuo-Feng, Bosetti, Cristina, Taylor, Jack A, Weiderpass, Elisabete, Grant, Eric J, White, Emily, Polesel, Jerry, and Zeegers, Maurice P A
Abstract: At present, analysis of diet and bladder cancer (BC) is mostly based on the intake of individual foods. The examination of food combinations provides a scope to deal with the complexity and unpredictability of the diet and aims to overcome the limitations of the study of nutrients and foods in isolation. This article aims to demonstrate the usability of supervised data mining methods to extract the food groups related to BC. In order to derive key food groups associated with BC risk, we applied the data mining technique C5.0 with 10-fold cross-validation in the BLadder cancer Epidemiology and Nutritional Determinants study, including data from eighteen case-control and one nested case-cohort study, compromising 8320 BC cases out of 31 551 participants. Dietary data, on the eleven main food groups of the Eurocode 2 Core classification codebook, and relevant non-diet data (i.e. sex, age and smoking status) were available. Primarily, five key food groups were extracted; in order of importance, beverages (non-milk); grains and grain products; vegetables and vegetable products; fats, oils and their products; meats and meat products were associated with BC risk. Since these food groups are corresponded with previously proposed BC-related dietary factors, data mining seems to be a promising technique in the field of nutritional epidemiology and deserves further examination.
Published: 2020
Full Text: View/download PDF

41. Education and gastric cancer risk-An individual participant data meta-analysis in the StoP project consortium

Author: Rota, Matteo, Alicandro, Gianfranco, Pelucchi, Claudio, Bonzi, Rossella, Bertuccio, Paola, Hu, Jinfu, Zhang, Zuo-Feng, Johnson, Kenneth C., Palli, Domenico, Ferraroni, Monica, Yu, Guo-Pei, Galeone, Carlotta, Lopez-Carrillo, Lizbeth, Muscat, Joshua, Lunet, Nuno, Ferro, Ana, Ye, Weimin, Plymoth, Amelie, Malekzadeh, Reza, Zaridze, David, Maximovitch, Dmitry, Kogevinas, Manolis, Fernandez de Larrea, Nerea, Vioque, Jesus, Navarrete-Munoz, Eva M., Tsugane, Shoichiro, Hamada, Gerson S., Hidaka, Akihisa, Pakseresht, Mohammadreza, Wolk, Alicja, Hakansson, Niclas, Hernandez-Ramirez, Raul Ulises, Lopez-Cervantes, Malaquias, Ward, Mary, Pourfarzi, Farhad, Mu, Lina, Kurtz, Robert C., Lagiou, Areti, Lagiou, Pagona, Boffetta, Paolo, Boccia, Stefania, Negri, Eva, La Vecchia, Carlo, Rota, Matteo, Alicandro, Gianfranco, Pelucchi, Claudio, Bonzi, Rossella, Bertuccio, Paola, Hu, Jinfu, Zhang, Zuo-Feng, Johnson, Kenneth C., Palli, Domenico, Ferraroni, Monica, Yu, Guo-Pei, Galeone, Carlotta, Lopez-Carrillo, Lizbeth, Muscat, Joshua, Lunet, Nuno, Ferro, Ana, Ye, Weimin, Plymoth, Amelie, Malekzadeh, Reza, Zaridze, David, Maximovitch, Dmitry, Kogevinas, Manolis, Fernandez de Larrea, Nerea, Vioque, Jesus, Navarrete-Munoz, Eva M., Tsugane, Shoichiro, Hamada, Gerson S., Hidaka, Akihisa, Pakseresht, Mohammadreza, Wolk, Alicja, Hakansson, Niclas, Hernandez-Ramirez, Raul Ulises, Lopez-Cervantes, Malaquias, Ward, Mary, Pourfarzi, Farhad, Mu, Lina, Kurtz, Robert C., Lagiou, Areti, Lagiou, Pagona, Boffetta, Paolo, Boccia, Stefania, Negri, Eva, and La Vecchia, Carlo
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. What's new? Gastric cancer is associated with low socioeconomic position but the precise impact of education on gastric cancer risk needs to be quantified. Here the authors provide an updated quantification through the analysis of the Stomach cancer Pooling (StoP) Project, a large international consortium of case-control studies. They observe a similar to 40% decrea
Published: 2020
Full Text: View/download PDF

42. Identifying Novel Susceptibility Genes for Colorectal Cancer Risk From a Transcriptome-Wide Association Study of 125,478 Subjects

Author: Guo, Xingyi, Lin, Weiqiang, Wen, Wanqing, Huyghe, Jeroen, Bien, Stephanie, Cai, Qiuyin, Harrison, Tabitha, Chen, Zhishan, Qu, Conghui, Bao, Jiandong, Long, Jirong, Yuan, Yuan, Wang, Fangqin, Bai, Mengqiu, Abecasis, Goncalo R, Albanes, Demetrius, Berndt, Sonja I, Bézieau, Stéphane, Bishop, D Timothy, Brenner, Hermann, Buch, Stephan, Burnett-Hartman, Andrea, Campbell, Peter T, Castellví-Bel, Sergi, Chan, Andrew T, Chang-Claude, Jenny, Chanock, Stephen J, Cho, Sang Hee, Conti, David V, Chapelle, Albert de la, Feskens, Edith J M, Gallinger, Steven J, Giles, Graham G, Goodman, Phyllis J, Gsur, Andrea, Guinter, Mark, Gunter, Marc J, Hampe, Jochen, Hampel, Heather, Hayes, Richard B, Hoffmeister, Michael, Kampman, Ellen, Kang, Hyun Min, Keku, Temitope O, Kim, Hyeong Rok, Le Marchand, Loic, Lee, Soo Chin, Li, Christopher I, Li, Li, Lindblom, Annika, Lindor, Noralane, Milne, Roger L, Moreno, Victor, Murphy, Neil, Newcomb, Polly A, Nickerson, Deborah A, Offit, Kenneth, Pearlman, Rachel, Pharoah, Paul D P, Platz, Elizabeth A, Potter, John D, Rennert, Gad, Sakoda, Lori C, Schafmayer, Clemens, Schmit, Stephanie L, Schoen, Robert E, Schumacher, Fredrick R, Slattery, Martha L, Su, Yu-Ru, Tangen, Catherine M, Ulrich, Cornelia M, van Duijnhoven, Franzel J B, Van Guelpen, Bethany, Visvanathan, Kala, Vodicka, Pavel, Vodickova, Ludmila, Vymetalkova, Veronika, Wang, Xiaolong, White, Emily, Wolk, Alicja, Woods, Michael O, Casey, Graham, Hsu, Li, Jenkins, Mark A, Gruber, Stephen B, Peters, Ulrike, Zheng, Wei, Guo, Xingyi, Lin, Weiqiang, Wen, Wanqing, Huyghe, Jeroen, Bien, Stephanie, Cai, Qiuyin, Harrison, Tabitha, Chen, Zhishan, Qu, Conghui, Bao, Jiandong, Long, Jirong, Yuan, Yuan, Wang, Fangqin, Bai, Mengqiu, Abecasis, Goncalo R, Albanes, Demetrius, Berndt, Sonja I, Bézieau, Stéphane, Bishop, D Timothy, Brenner, Hermann, Buch, Stephan, Burnett-Hartman, Andrea, Campbell, Peter T, Castellví-Bel, Sergi, Chan, Andrew T, Chang-Claude, Jenny, Chanock, Stephen J, Cho, Sang Hee, Conti, David V, Chapelle, Albert de la, Feskens, Edith J M, Gallinger, Steven J, Giles, Graham G, Goodman, Phyllis J, Gsur, Andrea, Guinter, Mark, Gunter, Marc J, Hampe, Jochen, Hampel, Heather, Hayes, Richard B, Hoffmeister, Michael, Kampman, Ellen, Kang, Hyun Min, Keku, Temitope O, Kim, Hyeong Rok, Le Marchand, Loic, Lee, Soo Chin, Li, Christopher I, Li, Li, Lindblom, Annika, Lindor, Noralane, Milne, Roger L, Moreno, Victor, Murphy, Neil, Newcomb, Polly A, Nickerson, Deborah A, Offit, Kenneth, Pearlman, Rachel, Pharoah, Paul D P, Platz, Elizabeth A, Potter, John D, Rennert, Gad, Sakoda, Lori C, Schafmayer, Clemens, Schmit, Stephanie L, Schoen, Robert E, Schumacher, Fredrick R, Slattery, Martha L, Su, Yu-Ru, Tangen, Catherine M, Ulrich, Cornelia M, van Duijnhoven, Franzel J B, Van Guelpen, Bethany, Visvanathan, Kala, Vodicka, Pavel, Vodickova, Ludmila, Vymetalkova, Veronika, Wang, Xiaolong, White, Emily, Wolk, Alicja, Woods, Michael O, Casey, Graham, Hsu, Li, Jenkins, Mark A, Gruber, Stephen B, Peters, Ulrike, and Zheng, Wei
Abstract: BACKGROUND AND AIMS: Susceptibility genes and the underlying mechanisms for the majority of risk loci identified by genome-wide association studies (GWAS) for colorectal cancer (CRC) risk remain largely unknown. We conducted a transcriptome-wide association study (TWAS) to identify putative susceptibility genes. METHODS: Gene-expression prediction models were built using transcriptome and genetic data from the 284 normal transverse colon tissues of European descendants from the Genotype-Tissue Expression (GTEx), and model performance was evaluated using data from The Cancer Genome Atlas (n = 355). We applied the gene-expression prediction models and GWAS data to evaluate associations of genetically predicted gene-expression with CRC risk in 58,131 CRC cases and 67,347 controls of European ancestry. Dual-luciferase reporter assays and knockdown experiments in CRC cells and tumor xenografts were conducted. RESULTS: We identified 25 genes associated with CRC risk at a Bonferroni-corrected threshold of P < 9.1 × 10-6, including genes in 4 novel loci, PYGL (14q22.1), RPL28 (19q13.42), CAPN12 (19q13.2), MYH7B (20q11.22), and MAP1L3CA (20q11.22). In 9 known GWAS-identified loci, we uncovered 9 genes that have not been reported previously, whereas 4 genes remained statistically significant after adjusting for the lead risk variant of the locus. Through colocalization analysis in GWAS loci, we additionally identified 12 putative susceptibility genes that were supported by TWAS analysis at P < .01. We showed that risk allele of the lead risk variant rs1741640 affected the promoter activity of CABLES2. Knockdown experiments confirmed that CABLES2 plays a vital role in colorectal carcinogenesis. CONCLUSIONS: Our study reveals new putative susceptibility genes and provides new insight into the biological mechanisms underlying CRC development.
Published: 2020
Full Text: View/download PDF

43. Cardiovascular and cancer mortality in relation to dietary polychlorinated biphenyls and marine polyunsaturated fatty acids : a nutritional-toxicological aspect of fish consumption

Author: Donat-Vargas, C., Bellavia, A., Berglund, M., Glynn, A., Wolk, Alicja, Akesson, A., Donat-Vargas, C., Bellavia, A., Berglund, M., Glynn, A., Wolk, Alicja, and Akesson, A.
Abstract: Background Co-exposure to environmental contaminants present in fish could mitigate the beneficial effects of fish consumption and possibly explain the lack of association observed for mortality in some geographical regions. Objective To assess the independent associations of dietary exposure to polychlorinated biphenyls (PCBs) and long-chain omega-3 fish fatty acids intake with cardiovascular and cancer mortality. Methods We used the prospective population-based Swedish Mammography Cohort and the Cohort of Swedish Men comprising 32 952 women and 36 545 men, free from cancer, cardiovascular disease and diabetes at baseline in 1998. Validated estimates of dietary PCBs and long-chain omega-3 fish fatty acids [i.e. eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] intake were obtained via a food frequency questionnaire at baseline. Information on death was ascertained through register linkage. Results During a mean follow-up of 15.5 years, we ascertained 16 776 deaths. We observed for cardiovascular mortality, comparing extreme quintiles in multivariable models mutually adjusted for PCBs and EPA-DHA, dose-dependent associations for dietary PCB exposure, hazard ratio (HR) 1.31 (CI 95%: 1.08 to 1.57; P-trend 0.005) and for dietary EPA-DHA intake, HR 0.79 (CI 95%: 0.66 to 0.95; P-trend 0.041). For cancer mortality, no clear associations were discerned. Conclusion The beneficial effect of fish consumption on the cardiovascular system seems compromised by co-exposure to PCBs - one likely explanation for the inconsistent associations observed between fish consumption and mortality.
Published: 2020
Full Text: View/download PDF

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

Author: Archambault, Alexi N., Su, Yu-Ru, Jeon, Jihyoun, Thomas, Minta, Lin, Yi, Conti, David V., Win, Aung Ko, Sakoda, Lori C., Lansdorp-Vogelaar, Iris, Peterse, Elisabeth F. P., Zauber, Ann G., Duggan, David, Holowatyj, Andreana N., Huyghe, Jeroen R., Brenner, Hermann, Cotterchio, Michelle, Bezieau, Stephane, Schmit, Stephanie L., Edlund, Christopher K., Southey, Melissa C., MacInnis, Robert J., Campbell, Peter T., Chang-Claude, Jenny, Slattery, Martha L., Chan, Andrew T., Joshi, Amit D., Song, Mingyang, Cao, Yin, Woods, Michael O., White, Emily, Weinstein, Stephanie J., Ulrich, Cornelia M., Hoffmeister, Michael, Bien, Stephanie A., Harrison, Tabitha A., Hampe, Jochen, Li, Christopher I., Schafmayer, Clemens, Offit, Kenneth, Pharoah, Paul D., Moreno, Victor, Lindblom, Annika, Wolk, Alicja, Wu, Anna H., Li, Li, Gunter, Marc J., Gsur, Andrea, Keku, Temitope O., Pearlman, Rachel, Bishop, D. Timothy, Castellvi-Bel, Sergi, Moreira, Leticia, Vodicka, Pavel, Kampman, Ellen, Giles, Graham G., Albanes, Demetrius, Baron, John A., Berndt, Sonja I., Brezina, Stefanie, Buch, Stephan, Buchanan, Daniel D., Trichopoulou, Antonia, Severi, Gianluca, Chirlaque, Maria-Dolores, Sanchez, Maria-Jose, Palli, Domenico, Kuhn, Tilman, Murphy, Neil, Cross, Amanda J., Burnett-Hartman, Andrea N., Chanock, Stephen J., de la Chapelle, Albert, Easton, Douglas F., Elliott, Faye, English, Dallas R., Feskens, Edith J. M., FitzGerald, Liesel M., Goodman, Phyllis J., Hopper, John L., Hudson, Thomas J., Hunter, David J., Jacobs, Eric J., Joshu, Corinne E., Kury, Sebastien, Markowitz, Sanford D., Milne, Roger L., Platz, Elizabeth A., Rennert, Gad, Rennert, Hedy S., Schumacher, Fredrick R., Sandler, Robert S., Seminara, Daniela, Tangen, Catherine M., Thibodeau, Stephen N., Toland, Amanda E., van Duijnhoven, Franzel J. B., Visvanathan, Kala, Vodickova, Ludmila, Potter, John D., Mannisto, Satu, Weigl, Korbinian, Figueiredo, Jane, Martin, Vicente, Larsson, Susanna C, Parfrey, Patrick S., Huang, Wen-Yi, Lenz, Heinz-Josef, Castelao, Jose E., Gago-Dominguez, Manuela, Munoz-Garzon, Victor, Mancao, Christoph, Haiman, Christopher A., Wilkens, Lynne R., Siegel, Erin, Barry, Elizabeth, Younghusband, Ban, Van Guelpen, Bethany, Harlid, Sophia, Zeleniuch-Jacquotte, Anne, Liang, Peter S., Du, Mengmeng, Casey, Graham, Lindor, Noralane M., Le Marchand, Loic, Gallinger, Steven J., Jenkins, Mark A., Newcomb, Polly A., Gruber, Stephen B., Schoen, Robert E., Hampel, Heather, Corley, Douglas A., Hsu, Li, Peters, Ulrike, Hayes, Richard B., Archambault, Alexi N., Su, Yu-Ru, Jeon, Jihyoun, Thomas, Minta, Lin, Yi, Conti, David V., Win, Aung Ko, Sakoda, Lori C., Lansdorp-Vogelaar, Iris, Peterse, Elisabeth F. P., Zauber, Ann G., Duggan, David, Holowatyj, Andreana N., Huyghe, Jeroen R., Brenner, Hermann, Cotterchio, Michelle, Bezieau, Stephane, Schmit, Stephanie L., Edlund, Christopher K., Southey, Melissa C., MacInnis, Robert J., Campbell, Peter T., Chang-Claude, Jenny, Slattery, Martha L., Chan, Andrew T., Joshi, Amit D., Song, Mingyang, Cao, Yin, Woods, Michael O., White, Emily, Weinstein, Stephanie J., Ulrich, Cornelia M., Hoffmeister, Michael, Bien, Stephanie A., Harrison, Tabitha A., Hampe, Jochen, Li, Christopher I., Schafmayer, Clemens, Offit, Kenneth, Pharoah, Paul D., Moreno, Victor, Lindblom, Annika, Wolk, Alicja, Wu, Anna H., Li, Li, Gunter, Marc J., Gsur, Andrea, Keku, Temitope O., Pearlman, Rachel, Bishop, D. Timothy, Castellvi-Bel, Sergi, Moreira, Leticia, Vodicka, Pavel, Kampman, Ellen, Giles, Graham G., Albanes, Demetrius, Baron, John A., Berndt, Sonja I., Brezina, Stefanie, Buch, Stephan, Buchanan, Daniel D., Trichopoulou, Antonia, Severi, Gianluca, Chirlaque, Maria-Dolores, Sanchez, Maria-Jose, Palli, Domenico, Kuhn, Tilman, Murphy, Neil, Cross, Amanda J., Burnett-Hartman, Andrea N., Chanock, Stephen J., de la Chapelle, Albert, Easton, Douglas F., Elliott, Faye, English, Dallas R., Feskens, Edith J. M., FitzGerald, Liesel M., Goodman, Phyllis J., Hopper, John L., Hudson, Thomas J., Hunter, David J., Jacobs, Eric J., Joshu, Corinne E., Kury, Sebastien, Markowitz, Sanford D., Milne, Roger L., Platz, Elizabeth A., Rennert, Gad, Rennert, Hedy S., Schumacher, Fredrick R., Sandler, Robert S., Seminara, Daniela, Tangen, Catherine M., Thibodeau, Stephen N., Toland, Amanda E., van Duijnhoven, Franzel J. B., Visvanathan, Kala, Vodickova, Ludmila, Potter, John D., Mannisto, Satu, Weigl, Korbinian, Figueiredo, Jane, Martin, Vicente, Larsson, Susanna C, Parfrey, Patrick S., Huang, Wen-Yi, Lenz, Heinz-Josef, Castelao, Jose E., Gago-Dominguez, Manuela, Munoz-Garzon, Victor, Mancao, Christoph, Haiman, Christopher A., Wilkens, Lynne R., Siegel, Erin, Barry, Elizabeth, Younghusband, Ban, Van Guelpen, Bethany, Harlid, Sophia, Zeleniuch-Jacquotte, Anne, Liang, Peter S., Du, Mengmeng, Casey, Graham, Lindor, Noralane M., Le Marchand, Loic, Gallinger, Steven J., Jenkins, Mark A., Newcomb, Polly A., Gruber, Stephen B., Schoen, Robert E., Hampel, Heather, Corley, Douglas A., Hsu, Li, Peters, Ulrike, and Hayes, Richard B.
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 x 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
Published: 2020
Full Text: View/download PDF

45. Breast Cancer Polygenic Risk Score and Contralateral Breast Cancer Risk

Author: Kramer, Iris, Hooning, Maartje J., Mavaddat, Nasim, Hauptmann, Michael, Keeman, Renske, Steyerberg, Ewout W., Giardiello, Daniele, Antoniou, Antonis C., Pharoah, Paul D. P., Canisius, Sander, Abu-Ful, Zumuruda, Andrulis, Irene L., Anton-Culver, Hoda, Aronson, Kristan J., Augustinsson, Annelie, Becher, Heiko, Beckmann, Matthias W., Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Bogdanova, Natalia, V, Bojesen, Stig E., Bolla, Manjeet K., Bonanni, Bernardo, Brauch, Hiltrud, Bremer, Michael, Brucker, Sara Y., Burwinkel, Barbara, Castelao, Jose E., Chan, Tsun L., Chang-Claude, Jenny, Chanock, Stephen J., Chenevix-Trench, Georgia, Choi, Ji-Yeob, Clarke, Christine L., Collee, J. Margriet, Couch, Fergus J., Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., Devilee, Peter, Dork, Thilo, dos-Santos-Silva, Isabel, Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Evans, D. Gareth, Fasching, Peter A., Flyger, Henrik, Gago-Dominguez, Manuela, Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Giles, Graham G., Goldgar, David E., Gonzalez-Neira, Anna, Haiman, Christopher A., Hakansson, Niclas, Hamann, Ute, Hartman, Mikael, Heemskerk-Gerritsen, Bernadette A. M., Hollestelle, Antoinette, Hopper, John L., Hou, Ming-Feng, Howell, Anthony, Ito, Hidemi, Jakimovska, Milena, Jakubowska, Anna, Janni, Wolfgang, John, Esther M., Jung, Audrey, Kang, Daehee, Kets, C. Marleen, Khusnutdinova, Elza, Ko, Yon-Dschun, Kristensen, Vessela N., Kurian, Allison W., Kwong, Ava, Lambrechts, Diether, Le Marchand, Loic, Li, Jingmei, Lindblom, Annika, Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Matsuo, Keitaro, Mavroudis, Dimitrios, Meindl, Alfons, Milne, Roger L., Mulligan, Anna Marie, Muranen, Taru A., Neuhausen, Susan L., Nevanlinna, Heli, Newman, William G., Olshan, Andrew F., Olson, Janet E., Olsson, Hakan, Park-Simon, Tjoung-Won, Peto, Julian, Petridis, Christos, Plaseska-Karanfilska, Dijana, Presneau, Nadege, Pylkas, Katri, Radice, Paolo, Rennert, Gad, Romero, Atocha, Roylance, Rebecca, Saloustros, Emmanouil, Sawyer, Elinor J., Schmutzler, Rita K., Schwentner, Lukas, Scott, Christopher, See, Mee-Hoong, Shah, Mitul, Shen, Chen-Yang, Shu, Xiao-Ou, Siesling, Sabine, Slager, Susan, Sohn, Christof, Southey, Melissa C., Spinelli, John J., Stone, Jennifer, Tapper, William J., Tengstrom, Maria, Teo, Soo Hwang, Terry, Mary Beth, Tollenaar, Rob A. E. M., Tomlinson, Ian, Troester, Melissa A., Vachon, Celine M., van Ongeval, Chantal, van Veen, Elke M., Winqvist, Robert, Wolk, Alicja, Zheng, Wei, Ziogas, Argyrios, Easton, Douglas F., Hall, Per, Schmidt, Marjanka K., Kramer, Iris, Hooning, Maartje J., Mavaddat, Nasim, Hauptmann, Michael, Keeman, Renske, Steyerberg, Ewout W., Giardiello, Daniele, Antoniou, Antonis C., Pharoah, Paul D. P., Canisius, Sander, Abu-Ful, Zumuruda, Andrulis, Irene L., Anton-Culver, Hoda, Aronson, Kristan J., Augustinsson, Annelie, Becher, Heiko, Beckmann, Matthias W., Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Bogdanova, Natalia, V, Bojesen, Stig E., Bolla, Manjeet K., Bonanni, Bernardo, Brauch, Hiltrud, Bremer, Michael, Brucker, Sara Y., Burwinkel, Barbara, Castelao, Jose E., Chan, Tsun L., Chang-Claude, Jenny, Chanock, Stephen J., Chenevix-Trench, Georgia, Choi, Ji-Yeob, Clarke, Christine L., Collee, J. Margriet, Couch, Fergus J., Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., Devilee, Peter, Dork, Thilo, dos-Santos-Silva, Isabel, Dunning, Alison M., Dwek, Miriam, Eccles, Diana M., Evans, D. Gareth, Fasching, Peter A., Flyger, Henrik, Gago-Dominguez, Manuela, Garcia-Closas, Montserrat, Garcia-Saenz, Jose A., Giles, Graham G., Goldgar, David E., Gonzalez-Neira, Anna, Haiman, Christopher A., Hakansson, Niclas, Hamann, Ute, Hartman, Mikael, Heemskerk-Gerritsen, Bernadette A. M., Hollestelle, Antoinette, Hopper, John L., Hou, Ming-Feng, Howell, Anthony, Ito, Hidemi, Jakimovska, Milena, Jakubowska, Anna, Janni, Wolfgang, John, Esther M., Jung, Audrey, Kang, Daehee, Kets, C. Marleen, Khusnutdinova, Elza, Ko, Yon-Dschun, Kristensen, Vessela N., Kurian, Allison W., Kwong, Ava, Lambrechts, Diether, Le Marchand, Loic, Li, Jingmei, Lindblom, Annika, Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Matsuo, Keitaro, Mavroudis, Dimitrios, Meindl, Alfons, Milne, Roger L., Mulligan, Anna Marie, Muranen, Taru A., Neuhausen, Susan L., Nevanlinna, Heli, Newman, William G., Olshan, Andrew F., Olson, Janet E., Olsson, Hakan, Park-Simon, Tjoung-Won, Peto, Julian, Petridis, Christos, Plaseska-Karanfilska, Dijana, Presneau, Nadege, Pylkas, Katri, Radice, Paolo, Rennert, Gad, Romero, Atocha, Roylance, Rebecca, Saloustros, Emmanouil, Sawyer, Elinor J., Schmutzler, Rita K., Schwentner, Lukas, Scott, Christopher, See, Mee-Hoong, Shah, Mitul, Shen, Chen-Yang, Shu, Xiao-Ou, Siesling, Sabine, Slager, Susan, Sohn, Christof, Southey, Melissa C., Spinelli, John J., Stone, Jennifer, Tapper, William J., Tengstrom, Maria, Teo, Soo Hwang, Terry, Mary Beth, Tollenaar, Rob A. E. M., Tomlinson, Ian, Troester, Melissa A., Vachon, Celine M., van Ongeval, Chantal, van Veen, Elke M., Winqvist, Robert, Wolk, Alicja, Zheng, Wei, Ziogas, Argyrios, Easton, Douglas F., Hall, Per, and Schmidt, Marjanka K.
Abstract: Previous research has shown that polygenic risk scores (PRSs) can be used to stratify women according to their risk of developing primary invasive breast cancer. This study aimed to evaluate the association between a recently validated PRS of 313 germline variants (PRS313) and contralateral breast cancer (CBC) risk. We included 56,068 women of European ancestry diagnosed with first invasive breast cancer from 1990 onward with follow-up from the Breast Cancer Association Consortium. Metachronous CBC risk (N = 1,027) according to the distribution of PRS313 was quantified using Cox regression analyses. We assessed PRS313 interaction with age at first diagnosis, family history, morphology, ER status, PR status, and HER2 status, and (neo)adjuvant therapy. In studies of Asian women, with limited follow-up, CBC risk associated with PRS313 was assessed using logistic regression for 340 women with CBC compared with 12,133 women with unilateral breast cancer. Higher PRS313 was associated with increased CBC risk: hazard ratio per standard deviation (SD) = 1.25 (95%CI = 1.18-1.33) for Europeans, and an OR per SD = 1.15 (95%CI = 1.02-1.29) for Asians. The absolute lifetime risks of CBC, accounting for death as competing risk, were 12.4% for European women at the 10th percentile and 20.5% at the 90th percentile of PRS313. We found no evidence of confounding by or interaction with individual characteristics, characteristics of the primary tumor, or treatment. The C-index for the PRS313 alone was 0.563 (95%CI = 0.547-0.586). In conclusion, PRS313 is an independent factor associated with CBC risk and can be incorporated into CBC risk prediction models to help improve stratification and optimize surveillance and treatment strategies.
Published: 2020
Full Text: View/download PDF

46. Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes

Author: Fachal, Laura, Wolk, Alicja, Sachchithananthan, Mythily, Fachal, Laura, Wolk, Alicja, and Sachchithananthan, Mythily
Abstract: Fine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions. Genome-wide association studies have identified breast cancer risk variants in over 150 genomic regions, but the mechanisms underlying risk remain largely unknown. These regions were explored by combining association analysis with in silico genomic feature annotations. We defined 205 independent risk-associated signals with the set of credible causal variants in each one. In parallel, we used a Bayesian approach (PAINTOR) that combines genetic association, linkage disequilibrium and enriched genomic features to determine variants with high posterior probabilities of being causal. Potentially causal variants were significantly over-represented in active gene regulatory regions and transcription factor binding sites. We applied our INQUSIT pipeline for prioritizing genes as targets of those potentially causal variants, using gene expression (expression quantitative trait loci), chromatin interaction and functional annotations. Known cancer drivers, transcription factors and genes in the developmental, apoptosis, immune system and DNA integrity checkpoint gene ontology pathways were over-represented among the highest-confidence target genes., For complete list of authors see http://dx.doi.org/10.1038/s41588-019-0537-1
Published: 2020
Full Text: View/download PDF

47. Anti-inflammatory diet and risk of heart failure : two prospective cohort studies

Author: Kaluza, Joanna, Levitan, Emily B., Michaëlsson, Karl, Wolk, Alicja, Kaluza, Joanna, Levitan, Emily B., Michaëlsson, Karl, and Wolk, Alicja
Abstract: Aim The impact of the anti‐inflammatory potential of diet on risk of heart failure (HF) and the potential modification of this association by smoking, a trigger of systemic inflammation, has not been previously investigated. We examined the association between anti‐inflammatory potential of diet and risk of HF taking into account smoking status. Methods and results The study population included the Cohort of Swedish Men (40 514 men) and the Swedish Mammography Cohort (34 809 women), age 45–83 years, without HF, ischaemic heart disease, or cancer at baseline. Anti‐inflammatory potential of diet was estimated using an anti‐inflammatory diet index (AIDI; 0–16 scores). Cox proportional hazard regression models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for HF risk factors. Over a mean follow‐up of 14.9 years (1 119 110 person‐years, 1998–2014), 8161 new HF diagnoses (4443 in men, 3718 in women) were identified. Compared to the lowest quintile of the AIDI (scores ≤4), the HRs for men and women in the highest quintile (scores ≥8) were 0.92 (95% CI 0.84–1.02; P‐trend = 0.02) and 0.86 (95% CI 0.78–0.96; P‐trend = 0.001), respectively. An inverse association between the AIDI and HF incidence was observed in current and ex‐smokers but not in never‐smokers (P‐interaction = 0.046). Comparing extreme quintiles, the HRs were 0.86 (95% CI 0.74–1.00; P‐trend = 0.007) in current smokers, 0.81 (95% CI 0.71–0.92; P‐trend = 0.001) in ex‐smokers, and 0.95 (95% CI 0.86–1.06; P‐trend = 0.10) in never‐smokers. Conclusion These results suggest that adherence to a diet with high anti‐inflammatory potential may be associated with lower HF incidence in current and ex‐smokers.
Published: 2020
Full Text: View/download PDF

48. Adult weight change and premenopausal breast cancer risk : A prospective pooled analysis of data from 628,463 women

Author: Schoemaker, Minouk J., Nichols, Hazel B., Wright, Lauren B., Brook, Mark N., Jones, Michael E., O'Brien, Katie M., Adami, Hans-Olov, Baglietto, Laura, Bernstein, Leslie, Bertrand, Kimberly A., Boutron-Ruault, Marie-Christine, Chen, Yu, Connor, Avonne E., Dossus, Laure, Eliassen, A. Heather, Giles, Graham G., Gram, Inger T., Hankinson, Susan E., Kaaks, Rudolf, Key, Timothy J., Kirsh, Victoria A., Kitahara, Cari M., Larsson, Susanna C., Linet, Martha, Ma, Huiyan, Milne, Roger L., Ozasa, Kotaro, Palmer, Julie R., Riboli, Elio, Rohan, Thomas E., Sacerdote, Carlotta, Sadakane, Atsuko, Sund, Malin, Tamimi, Rulla M., Trichopoulou, Antonia, Ursin, Giske, Visvanathan, Kala, Weiderpass, Elisabete, Willett, Walter C., Wolk, Alicja, Zeleniuch-Jacquotte, Anne, Sandler, Dale P., Swerdlow, Anthony J., Schoemaker, Minouk J., Nichols, Hazel B., Wright, Lauren B., Brook, Mark N., Jones, Michael E., O'Brien, Katie M., Adami, Hans-Olov, Baglietto, Laura, Bernstein, Leslie, Bertrand, Kimberly A., Boutron-Ruault, Marie-Christine, Chen, Yu, Connor, Avonne E., Dossus, Laure, Eliassen, A. Heather, Giles, Graham G., Gram, Inger T., Hankinson, Susan E., Kaaks, Rudolf, Key, Timothy J., Kirsh, Victoria A., Kitahara, Cari M., Larsson, Susanna C., Linet, Martha, Ma, Huiyan, Milne, Roger L., Ozasa, Kotaro, Palmer, Julie R., Riboli, Elio, Rohan, Thomas E., Sacerdote, Carlotta, Sadakane, Atsuko, Sund, Malin, Tamimi, Rulla M., Trichopoulou, Antonia, Ursin, Giske, Visvanathan, Kala, Weiderpass, Elisabete, Willett, Walter C., Wolk, Alicja, Zeleniuch-Jacquotte, Anne, Sandler, Dale P., and Swerdlow, Anthony J.
Abstract: Early-adulthood body size is strongly inversely associated with risk of premenopausal breast cancer. It is unclear whether subsequent changes in weight affect risk. We pooled individual-level data from 17 prospective studies to investigate the association of weight change with premenopausal breast cancer risk, considering strata of initial weight, timing of weight change, other breast cancer risk factors and breast cancer subtype. Hazard ratios (HR) and 95% confidence intervals (CI) were obtained using Cox regression. Among 628,463 women, 10,886 were diagnosed with breast cancer before menopause. Models adjusted for initial weight at ages 18-24 years and other breast cancer risk factors showed that weight gain from ages 18-24 to 35-44 or to 45-54 years was inversely associated with breast cancer overall (e.g., HR per 5 kg to ages 45-54: 0.96, 95% CI: 0.95-0.98) and with oestrogen-receptor(ER)-positive breast cancer (HR per 5 kg to ages 45-54: 0.96, 95% CI: 0.94-0.98). Weight gain from ages 25-34 was inversely associated with ER-positive breast cancer only and weight gain from ages 35-44 was not associated with risk. None of these weight gains were associated with ER-negative breast cancer. Weight loss was not consistently associated with overall or ER-specific risk after adjusting for initial weight. Weight increase from early-adulthood to ages 45-54 years is associated with a reduced premenopausal breast cancer risk independently of early-adulthood weight. Biological explanations are needed to account for these two separate factors.
Published: 2020
Full Text: View/download PDF

49. Ovarian Cancer Risk Factor Associations by Primary Anatomic Site : The Ovarian Cancer Cohort Consortium

Author: Fortner, Renee T., Rice, Megan S., Knutsen, Synnove F., Orlich, Michael J., Visvanathan, Kala, Patel, Alpa, V, Gaudet, Mia M., Tjønneland, Anne, Kvaskoff, Marina, Kaaks, Rudolf, Trichopolou, Antonia, Pala, Valeria, Onland-Moret, N. Charlotte, Gram, Inger T., Amiano, Pilar, Idahl, Annika, Allen, Naomi E., Weiderpass, Elisabete, Poynter, Jenny N., Robien, Kim, Giles, Graham G., Milne, Roger L., Setiawan, Veronica W., Merritt, Melissa A., van den Brandt, Piet A., Zeleniuch-Jacquotte, Anne, Arslan, Alan A., O'Brien, Katie M., Sandler, Dale P., Wolk, Alicja, Håkansson, Niclas, Harris, Holly R., Trabert, Britton, Wentzensen, Nicolas, Tworoger, Shelley S., Schouten, Leo J., Fortner, Renee T., Rice, Megan S., Knutsen, Synnove F., Orlich, Michael J., Visvanathan, Kala, Patel, Alpa, V, Gaudet, Mia M., Tjønneland, Anne, Kvaskoff, Marina, Kaaks, Rudolf, Trichopolou, Antonia, Pala, Valeria, Onland-Moret, N. Charlotte, Gram, Inger T., Amiano, Pilar, Idahl, Annika, Allen, Naomi E., Weiderpass, Elisabete, Poynter, Jenny N., Robien, Kim, Giles, Graham G., Milne, Roger L., Setiawan, Veronica W., Merritt, Melissa A., van den Brandt, Piet A., Zeleniuch-Jacquotte, Anne, Arslan, Alan A., O'Brien, Katie M., Sandler, Dale P., Wolk, Alicja, Håkansson, Niclas, Harris, Holly R., Trabert, Britton, Wentzensen, Nicolas, Tworoger, Shelley S., and Schouten, Leo J.
Abstract: Background: Epithelial ovarian, fallopian tube, and primary peritoneal cancers have shared developmental pathways. Few studies have prospectively examined heterogeneity in risk factor associations across these three anatomic sites. Methods: We identified 3,738 ovarian, 337 peritoneal, and 176 fallopian tube incident cancer cases in 891,731 women from 15 prospective cohorts in the Ovarian Cancer Cohort Consortium. Associations between 18 putative risk factors and risk of ovarian, peritoneal, and fallopian tube cancer, overall and for serous and high-grade serous tumors, were evaluated using competing risks Cox proportional hazards regression. Heterogeneity was assessed by likelihood ratio tests. Results: Most associations did not vary by tumor site (P-het = 0.05). Associations between first pregnancy (P-het = 0.04), tubal ligation (P-het = 0.01), and early-adult (age 18-21 years) body mass index (BMI; P-het = 0.02) and risk differed between ovarian and peritoneal cancers. The association between early-adult BMI and risk further differed between peritoneal and fallopian tube cancer (P-het = 0.03). First pregnancy and tubal ligation were inversely associated with ovarian, but not peritoneal, cancer. Higher early-adult BMI was associated with higher risk of peritoneal, but not ovarian or fallopian tube, cancer. Patterns were generally similar when restricted to serous and high-grade serous cases. Conclusions: Ovarian, fallopian tube, and primary peritoneal cancers appear to have both shared and distinct etiologic pathways, although most risk factors appear to have similar associations by anatomic site. Impact: Further studies on the mechanisms underlying the differences in risk profiles may provide insights regarding the developmental origins of tumors arising in the peritoneal cavity and inform prevention efforts.
Published: 2020
Full Text: View/download PDF

50. Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses

Author: Zhan, Haoyu, Ahearn, Thomas U., Lecarpentier, Julie, Barnes, Daniel, Beesley, Jonathan, Qi, Guanghao, Hang, Xia, O'Mara, Tracy A., Zhao, Ni, Bolla, Manjeet K., Dunning, Alison M., Dennis, Joe, Wang, Qin, Abu Ful, Zumuruda, Aittomaki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Aronson, Kristan J., Arun, Banu K., Auer, Paul L., Azzollini, Jacopo, Barrowdale, Daniel, Becher, Heiko, Beckmann, Matthias W., Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Bialkowska, Katarzyna, Blanco, Ana, Blomqvist, Carl, Bogdanova, Natalia, V, Bojesen, Stig E., Bonanni, Bernardo, Bondavalli, Davide, Borg, Ake, Brauch, Hiltrud, Brenner, Hermann, Briceno, Ignacio, Broeks, Annegien, Brucker, Sara Y., Bruening, Thomas, Burwinkel, Barbara, Buys, Saundra S., Byers, Helen, Caldes, Trinidad, Caligo, Maria A., Calvello, Mariarosaria, Campa, Daniele, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Christiaens, Melissa, Christiansen, Hans, Chung, Wendy K., Claes, Kathleen B. M., Clarke, Christine L., Cornelissen, Sten, Couch, Fergus J., Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., Devilee, Peter, Diez, Orland, Domchek, Susan M., Doerk, Thilo, Dwek, Miriam, Eccles, Diana M., Ekici, Arif B., Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine, Foretova, Lenka, Fostira, Florentia, Friedman, Eitan, Frost, Debra, Gago-Dominguez, Manuela, Gapstur, Susan M., Garber, Judy, Garcia-Saenz, Jose A., Gaudet, Mia M., Gayther, Simon A., Giles, Graham G., Godwin, Andrew K., Goldberg, Mark S., Goldgar, David E., Gonzalez-Neira, Anna, Greene, Mark H., Gronwald, Jacek, Guenel, Pascal, Haeberle, Lothar, Hahnen, Eric, Haiman, Christopher A., Hake, Christopher R., Hall, Per, Hamann, Ute, Harkness, Elaine F., Heemskerk-Gerritsen, Bernadette A. M., Hillemanns, Peter, Hogervorst, Frans B. L., Holleczek, Bernd, Hollestelle, Antoinette, Hooning, Maartje J., Hoover, Robert N., Hopper, John L., Howell, Anthony, Huebner, Hanna, Hulick, Peter J., Imyanitov, Evgeny N., Isaacs, Claudine, Izatt, Louise, Jager, Agnes, Jakimovska, Milena, Jakubowska, Anna, James, Paul, Janavicius, Ramunas, Janni, Wolfgang, John, Esther M., Jones, Michael E., Jung, Audrey, Kaaks, Rudolf, Kapoor, Pooja Middha, Karlan, Beth Y., Keeman, Renske, Khan, Sofia, Khusnutdinova, Elza, Kitahara, Cari M., Ko, Yon-Dschun, Konstantopoulou, Irene, Koppert, Linetta B., Koutros, Stella, Kristensen, Vessela N., Laenkholm, Anne-Vibeke, Lambrechts, Diether, Larsson, Susanna C., Laurent-Puig, Pierre, Lazaro, Conxi, Lazarova, Emilija, Lejbkowicz, Flavio, Leslie, Goska, Lesueur, Fabienne, Lindblom, Annika, Lissowska, Jolanta, Lo, Wing-Yee, Loud, Jennifer T., Lubinski, Jan, Lukomska, Alicja, Maclnnis, Robert J., Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush, Margolin, Sara, Martinez, Maria Elena, Matricardi, Laura, McGuffog, Lesley, McLean, Catriona, Mebirouk, Noura, Meindl, Alfons, Menon, Usha, Miller, Austin, Mingazheva, Elvira, Montagna, Marco, Mulligan, Anna Marie, Mulot, Claire, Muranen, Taru A., Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Neven, Patrick, Newman, William G., Nielsens, Finn C., Nikitina-Zake, Liene, Nodora, Jesse, Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo, I, Olsson, Hakan, Orr, Nick, Papi, Laura, Papp, Janos, Park-Simon, Tjoung-Won, Parsons, Michael T., Peissel, Bernard, Peixoto, Ana, Peshkin, Beth, Peterlongo, Paolo, Peto, Julian, Phillips, Kelly-Anne, Piedmonte, Marion, Plaseska-Karanfilska, Dijana, Prajzendanc, Karolina, Prentice, Ross, Prokofyeva, Darya, Rack, Brigitte, Radice, Paolo, Ramus, Susan J., Rantala, Johanna, Rashid, Muhammad U., Rennert, Gad, Rennert, Hedy S., Risch, Harvey A., Romero, Atocha, Rookus, Matti A., Ruebner, Matthias, Ruediger, Thomas, Saloustros, Emmanouil, Sampson, Sarah, Sandler, Dale P., Sawyer, Elinor J., Scheuner, Maren T., Schmutzler, Rita K., Schneeweiss, Andreas, Schoemaker, Minouk J., Schoettker, Ben, Schuermann, Peter, Senter, Leigha, Sharma, Priyanka, Sherman, Mark E., Shu, Xiao-Ou, Singer, Christian F., Smichkoska, Snezhana, Soucy, Penny, Southey, Melissa C., Spinelli, John J., Stone, Jennifer, Stoppa-Lyonnet, Dominique, Swerdlow, Anthony J., Szabo, Csilla, I, Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teixeira, Manuel R., Terry, MaryBeth, Thomassen, Mads, Thull, Darcy L., Tischkowitz, Marc, Toland, Amanda E., Tollenaar, Rob A. E. M., Tomlinson, Ian, Torres, Diana, Troester, Melissa A., Truong, Therese, Tung, Nadine, Untch, Michael, Vachon, Celine M., van den Ouweland, Ans M. W., van der Kolk, Lizet E., van Veen, Elke M., vanRensburg, Elizabeth J., Vega, Ana, Wappenschmidt, Barbara, Weinberg, Clarice R., Weitzel, Jeffrey N., Wildiers, Hans, Winqvist, Robert, Wolk, Alicja, Yang, Xiaohong R., Yannoukakos, Drakoulis, Zheng, Wei, Zorn, Kristin K., Milne, Roger L., Kraft, Peter, Simard, Jacques, Pharoah, Paul D. P., Michailidou, Kyriaki, Antoniou, Antonis C., Schmidt, Marjanka K., Chenevix-Trench, Georgia, Easton, Douglas F., Chatterjee, Nilanjan, Garcia-Closas, Montserrat, Zhan, Haoyu, Ahearn, Thomas U., Lecarpentier, Julie, Barnes, Daniel, Beesley, Jonathan, Qi, Guanghao, Hang, Xia, O'Mara, Tracy A., Zhao, Ni, Bolla, Manjeet K., Dunning, Alison M., Dennis, Joe, Wang, Qin, Abu Ful, Zumuruda, Aittomaki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Aronson, Kristan J., Arun, Banu K., Auer, Paul L., Azzollini, Jacopo, Barrowdale, Daniel, Becher, Heiko, Beckmann, Matthias W., Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Bialkowska, Katarzyna, Blanco, Ana, Blomqvist, Carl, Bogdanova, Natalia, V, Bojesen, Stig E., Bonanni, Bernardo, Bondavalli, Davide, Borg, Ake, Brauch, Hiltrud, Brenner, Hermann, Briceno, Ignacio, Broeks, Annegien, Brucker, Sara Y., Bruening, Thomas, Burwinkel, Barbara, Buys, Saundra S., Byers, Helen, Caldes, Trinidad, Caligo, Maria A., Calvello, Mariarosaria, Campa, Daniele, Castelao, Jose E., Chang-Claude, Jenny, Chanock, Stephen J., Christiaens, Melissa, Christiansen, Hans, Chung, Wendy K., Claes, Kathleen B. M., Clarke, Christine L., Cornelissen, Sten, Couch, Fergus J., Cox, Angela, Cross, Simon S., Czene, Kamila, Daly, Mary B., Devilee, Peter, Diez, Orland, Domchek, Susan M., Doerk, Thilo, Dwek, Miriam, Eccles, Diana M., Ekici, Arif B., Evans, D. Gareth, Fasching, Peter A., Figueroa, Jonine, Foretova, Lenka, Fostira, Florentia, Friedman, Eitan, Frost, Debra, Gago-Dominguez, Manuela, Gapstur, Susan M., Garber, Judy, Garcia-Saenz, Jose A., Gaudet, Mia M., Gayther, Simon A., Giles, Graham G., Godwin, Andrew K., Goldberg, Mark S., Goldgar, David E., Gonzalez-Neira, Anna, Greene, Mark H., Gronwald, Jacek, Guenel, Pascal, Haeberle, Lothar, Hahnen, Eric, Haiman, Christopher A., Hake, Christopher R., Hall, Per, Hamann, Ute, Harkness, Elaine F., Heemskerk-Gerritsen, Bernadette A. M., Hillemanns, Peter, Hogervorst, Frans B. L., Holleczek, Bernd, Hollestelle, Antoinette, Hooning, Maartje J., Hoover, Robert N., Hopper, John L., Howell, Anthony, Huebner, Hanna, Hulick, Peter J., Imyanitov, Evgeny N., Isaacs, Claudine, Izatt, Louise, Jager, Agnes, Jakimovska, Milena, Jakubowska, Anna, James, Paul, Janavicius, Ramunas, Janni, Wolfgang, John, Esther M., Jones, Michael E., Jung, Audrey, Kaaks, Rudolf, Kapoor, Pooja Middha, Karlan, Beth Y., Keeman, Renske, Khan, Sofia, Khusnutdinova, Elza, Kitahara, Cari M., Ko, Yon-Dschun, Konstantopoulou, Irene, Koppert, Linetta B., Koutros, Stella, Kristensen, Vessela N., Laenkholm, Anne-Vibeke, Lambrechts, Diether, Larsson, Susanna C., Laurent-Puig, Pierre, Lazaro, Conxi, Lazarova, Emilija, Lejbkowicz, Flavio, Leslie, Goska, Lesueur, Fabienne, Lindblom, Annika, Lissowska, Jolanta, Lo, Wing-Yee, Loud, Jennifer T., Lubinski, Jan, Lukomska, Alicja, Maclnnis, Robert J., Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush, Margolin, Sara, Martinez, Maria Elena, Matricardi, Laura, McGuffog, Lesley, McLean, Catriona, Mebirouk, Noura, Meindl, Alfons, Menon, Usha, Miller, Austin, Mingazheva, Elvira, Montagna, Marco, Mulligan, Anna Marie, Mulot, Claire, Muranen, Taru A., Nathanson, Katherine L., Neuhausen, Susan L., Nevanlinna, Heli, Neven, Patrick, Newman, William G., Nielsens, Finn C., Nikitina-Zake, Liene, Nodora, Jesse, Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo, I, Olsson, Hakan, Orr, Nick, Papi, Laura, Papp, Janos, Park-Simon, Tjoung-Won, Parsons, Michael T., Peissel, Bernard, Peixoto, Ana, Peshkin, Beth, Peterlongo, Paolo, Peto, Julian, Phillips, Kelly-Anne, Piedmonte, Marion, Plaseska-Karanfilska, Dijana, Prajzendanc, Karolina, Prentice, Ross, Prokofyeva, Darya, Rack, Brigitte, Radice, Paolo, Ramus, Susan J., Rantala, Johanna, Rashid, Muhammad U., Rennert, Gad, Rennert, Hedy S., Risch, Harvey A., Romero, Atocha, Rookus, Matti A., Ruebner, Matthias, Ruediger, Thomas, Saloustros, Emmanouil, Sampson, Sarah, Sandler, Dale P., Sawyer, Elinor J., Scheuner, Maren T., Schmutzler, Rita K., Schneeweiss, Andreas, Schoemaker, Minouk J., Schoettker, Ben, Schuermann, Peter, Senter, Leigha, Sharma, Priyanka, Sherman, Mark E., Shu, Xiao-Ou, Singer, Christian F., Smichkoska, Snezhana, Soucy, Penny, Southey, Melissa C., Spinelli, John J., Stone, Jennifer, Stoppa-Lyonnet, Dominique, Swerdlow, Anthony J., Szabo, Csilla, I, Tamimi, Rulla M., Tapper, William J., Taylor, Jack A., Teixeira, Manuel R., Terry, MaryBeth, Thomassen, Mads, Thull, Darcy L., Tischkowitz, Marc, Toland, Amanda E., Tollenaar, Rob A. E. M., Tomlinson, Ian, Torres, Diana, Troester, Melissa A., Truong, Therese, Tung, Nadine, Untch, Michael, Vachon, Celine M., van den Ouweland, Ans M. W., van der Kolk, Lizet E., van Veen, Elke M., vanRensburg, Elizabeth J., Vega, Ana, Wappenschmidt, Barbara, Weinberg, Clarice R., Weitzel, Jeffrey N., Wildiers, Hans, Winqvist, Robert, Wolk, Alicja, Yang, Xiaohong R., Yannoukakos, Drakoulis, Zheng, Wei, Zorn, Kristin K., Milne, Roger L., Kraft, Peter, Simard, Jacques, Pharoah, Paul D. P., Michailidou, Kyriaki, Antoniou, Antonis C., Schmidt, Marjanka K., Chenevix-Trench, Georgia, Easton, Douglas F., Chatterjee, Nilanjan, and Garcia-Closas, Montserrat
Abstract: Genome-wide analysis identifies 32 loci associated with breast cancer susceptibility, accounting for estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype(1-3). To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (P < 5.0 x 10(-8)), 15 of which showed evidence for associations with at least one tumor feature (false discovery rate < 0.05). Five loci showed associations (P < 0.05) in opposite directions between luminal and non-luminal subtypes. In silico analyses showed that these five loci contained cell-specific enhancers that differed between normal luminal and basal mammary cells. The genetic correlations between five intrinsic-like subtypes ranged from 0.35 to 0.80. The proportion of genome-wide chip heritability explained by all known susceptibility loci was 54.2% for luminal A-like disease and 37.6% for triple-negative disease. The odds ratios of polygenic risk scores, which included 330 variants, for the highest 1% of quantiles compared with middle quantiles were 5.63 and 3.02 for luminal A-like and triple-negative disease, respectively. These findings provide an improved understanding of genetic predisposition to breast cancer subtypes and will inform the development of subtype-specific polygenic risk scores.
Published: 2020
Full Text: View/download PDF

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Database

Publisher

519 results on '"Wolk A."'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources