Journal article

Associations of obesity and circulating insulin and glucose with breast cancer risk: a Mendelian randomization analysis

Xiang Shu, Lang Wu, Nikhil K Khankari, Xiao-Ou Shu, Thomas J Wang, Kyriaki Michailidou, Manjeet K Bolla, Qin Wang, Joe Dennis, Roger L Milne, Marjanka K Schmidt, Paul DP Pharoah, Irene L Andrulis, David J Hunter, Jacques Simard, Douglas F Easton, Wei Zheng, Beeghly-Fadiel J Alicia, Hoda Anton-Culver, Natalia N Antonenkova Show all

International Journal of Epidemiology | OXFORD UNIV PRESS | Published : 2019

Abstract

Background: In addition to the established association between general obesity and breast cancer risk, central obesity and circulating fasting insulin and glucose have been linked to the development of this common malignancy. Findings from previous studies, however, have been inconsistent, and the nature of the associations is unclear. Methods: We conducted Mendelian randomization analyses to evaluate the association of breast cancer risk, using genetic instruments, with fasting insulin, fasting glucose, 2-h glucose, body mass index (BMI) and BMI-adjusted waist-hip-ratio (WHRadj BMI). We first confirmed the association of these instruments with type 2 diabetes risk in a large diabetes genome..

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Grants

Awarded by National Cancer Institute at the National Institutes of Health


Awarded by National Cancer Institute Genetic Associations and Mechanisms in Oncology (GAME-ON) initiative and Discovery, Biology and Risk of Inherited Variants in Breast Cancer (DRIVE) project


Awarded by Cancer Research UK


Awarded by European Community


Awarded by European Union


Awarded by Ministry of Economic Development, Innovation and Export Trade of Quebec


Awarded by National Institute of Health (NIH) Cancer Post-Cancer GWAS initiative


Funding Acknowledgements

This work at Vanderbilt University Medical Center was supported in part by the National Cancer Institute at the National Institutes of Health [grant numbers R01CA158473, R01CA148677], as well as funds from Anne Potter Wilson endowment to W.Z. Genotyping of the OncoArray was principally funded from three sources: the PERSPECTIVE project, funded from the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the Ministere de l'Economie, de la Science et de l'Innovation du Quebec through Genome Quebec, and the Quebec Breast Cancer Foundation; the National Cancer Institute Genetic Associations and Mechanisms in Oncology (GAME-ON) initiative and Discovery, Biology and Risk of Inherited Variants in Breast Cancer (DRIVE) project [grant numbers U19CA148065, X01HG007492); and Cancer Research UK [grant numbersC1287/A10118, C1287/A16563]. BCAC is funded by Cancer Research UK [grant number C1287/A16563], the European Community's Seventh Framework Programme [grant number 223175 (HEALTH-F2-2009-223175) (COGS)] and by the European Union's Horizon 2020 Research and Innovation Programme [grant agreements 633784 (B-CAST) and 634935 (BRIDGES)]. Genotyping of the iCOGS array was funded by the European Union [HEALTH-F2-2009-223175], Cancer Research UK [C1287/A10710], the Canadian Institutes of Health Research for the 'CIHR Team in Familial Risks of Breast Cancer' program, and the Ministry of Economic Development, Innovation and Export Trade of Quebec [PSR-SIIRI-701]. Combining the GWAS data was supported in part by the National Institute of Health (NIH) Cancer Post-Cancer GWAS initiative [grant number U19CA148065; DRIVE, part of the GAME-ON initiative]. For a full description of funding and acknowledgments, see Supplementary Note, available as Supplementary data at IJE online. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.