期刊
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
卷 45, 期 3, 页码 896-908出版社
OXFORD UNIV PRESS
DOI: 10.1093/ije/dyw129
关键词
Cancer risk; body mass index; waist-to-hip ratio; Mendelian randomization; post-GWAS study
资金
- Genetic Associations and Mechanisms in Oncology Network, GAME-ON [U19 CA148107]
- Discovery, Biology, and Risk of Inherited Variants in Breast Cancer, DRIVE [U19 CA148065]
- Elucidating Loci Involved in Prostate Cancer Susceptibility, ELLIPSE [U19 CA148537]
- Follow-up of Ovarian Cancer genetic association and Interaction studies, FOCI [U19 CA148112]
- Transdisciplinary Research in Cancer of the Lung, TRICL [U19 CA148127]
- Pharmaceutical Research and Manufacturers of America (PhRMA) Foundation [NIEHS K99ES023504, NIEHS R21 ES025052]
- Cancer Research UK [C1287/A16563, C150/A5660, C1178/A3947, C490/A8339]
- National Institutes of Health [CA173785, CA165131]
- Breakthrough Breast Cancer
- Institut National de Cancer
- National Health Service
- Wellcome Trust [076113, 085475]
- Netherlands Organisation of Scientific Research NWO Investments [175.010.2005.011, 911-03-012]
- Genetic Laboratory of the Department of Internal Medicine
- Erasmus MC
- Research Institute for Diseases in the Elderly [014-93-015, RIDE2]
- Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO)
- Netherlands Consortium for Healthy Aging (NCHA) [050-060-810]
- Erasmus Medical Center and Erasmus University, Rotterdam
- Netherlands Organization for the Health Research and Development (ZonMw)
- Research Institute for Diseases in the Elderly (RIDE)
- Ministry of Education, Culture and Science
- Ministry for Health, Welfare and Sports
- European Commission (DGx II)
- Municipality of Rotterdam
- Follow-up of Ovarian Cancer Genetic Association and Interaction Studies (FOCI): the National Cancer Institute's Cancer Post-GWAS Initiative
- Genetic Associations and Mechanisms in Oncology (GAME-ON) [U19-CA148112, R01-CA114343, R01-CA114343-S1]
- National Cancer Institute [P30-CA15083]
- Cancer Research UK [16563] Funding Source: researchfish
Background: Adiposity traits have been associated with risk of many cancers in observational studies, but whether these associations are causal is unclear. Mendelian randomization (MR) uses genetic predictors of risk factors as instrumental variables to eliminate reverse causation and reduce confounding bias. We performed MR analyses to assess the possible causal relationship of birthweight, childhood and adult body mass index (BMI), and waist-hip ratio (WHR) on the risks of breast, ovarian, prostate, colorectal and lung cancers. Methods: We tested the association between genetic risk scores and each trait using summary statistics from published genome-wide association studies (GWAS) and from 51 537 cancer cases and 61 600 controls in the Genetic Associations and Mechanisms in Oncology (GAME-ON) Consortium. Results: We found an inverse association between the genetic score for childhood BMI and risk of breast cancer [odds ratio (OR) = 0.71 per standard deviation (s.d.) increase in childhood BMI; 95% confidence interval (CI): 0.60, 0.80; P = 6.5 x 10(-5)). We also found the genetic score for adult BMI to be inversely associated with breast cancer risk (OR = 0.66 per s.d. increase in BMI; 95% CI: 0.57, 0.77; P = 2.5 x 10(-7)), and positively associated with ovarian cancer (OR = 1.35; 95% CI: 1.05, 1.72; P = 0.017), lung cancer (OR = 1.27; 95% CI: 1.09, 1.49; P = 2.9 x 10(-3)) and colorectal cancer (OR = 1.39; 95% CI: 1.06, 1.82, P = 0.016). The inverse association between genetically predicted adult BMI and breast cancer risk remained even after adjusting for directional pleiotropy via MR-Egger regression. Conclusions: Findings from this study provide additional understandings of the complex relationship between adiposity and cancer risks. Our results for breast and lung cancer are particularly interesting, given previous reports of effect heterogeneity by menopausal status and smoking status.
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