Journal article

The influence of obesity-related factors in the etiology of renal cell carcinoma-A mendelian randomization study

Mattias Johansson, Robert Carreras-Torres, Ghislaine Scelo, Mark P Purdue, Daniela Mariosa, David C Muller, Nicolas J Timpson, Philip C Haycock, Kevin M Brown, Zhaoming Wang, Yuanqing Ye, Jonathan N Hofmann, Matthieu Foll, Valerie Gaborieau, Mitchell J Machiela, Leandro M Colli, Peng Li, Jean-Guillaume Garnier, Helene Blanche, Anne Boland Show all

PLOS MEDICINE | PUBLIC LIBRARY SCIENCE | Published : 2019

Abstract

BACKGROUND: Several obesity-related factors have been associated with renal cell carcinoma (RCC), but it is unclear which individual factors directly influence risk. We addressed this question using genetic markers as proxies for putative risk factors and evaluated their relation to RCC risk in a mendelian randomization (MR) framework. This methodology limits bias due to confounding and is not affected by reverse causation. METHODS AND FINDINGS: Genetic markers associated with obesity measures, blood pressure, lipids, type 2 diabetes, insulin, and glucose were initially identified as instrumental variables, and their association with RCC risk was subsequently evaluated in a genome-wide assoc..

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Grants

Awarded by World Cancer Research Fund International


Awarded by Cancer Research UK


Awarded by US National Institutes of Health (NIH), National Cancer Institute


Awarded by NIH


Awarded by MRC Integrative Epidemiology Unit at the University of Bristol


Funding Acknowledgements

This analysis was supported by the World Cancer Research Fund International-https://www.wcrf.org/(2014/1193, to MJ) and Cancer Research UK-https://www.cancerresearchuk.org/(C18281/A19169, to RMM and CR). Funding for the genome-wide genotyping was provided by the US National Institutes of Health (NIH), National Cancer Institute-https://www.cancer.gov (U01CA155309) for those studies coordinated by IARC, and by the intramural research program of the National Cancer Institute, US NIH, for those studies coordinated by the NCI; and the MD Anderson GWAS was supported in part by the NIH (grant R01 CA170298) and the Center for Translational and Public Health Genomics, Duncan Family Institute for Cancer Prevention and Risk Assessment, The University of Texas MD Anderson Cancer Center. RMM is supported by the National Institute for Health Research (NIHR) Bristol Nutritional Biomedical Research Unit based at University Hospitals Bristol NHS Foundation Trust and the University of Bristol. RCT, PCH, CR, RMM, GDS, MJ, and PB are investigators or researchers on a Cancer Research UK (C18281/A19169) Programme Grant (the Integrative Cancer Epidemiology Programme). CR, GDS, and NT work within the MRC Integrative Epidemiology Unit at the University of Bristol (MC_UU_12013/1, MC_UU_12013/2, MC_UU_12013/3). JBR is supported by the Canadian Institutes of Health Research and the Fonds du Recherche Quebec-Sante. JL is supported by the RM/ICR NIHR Biomedical Research Centre for Cancer. The funders had no role in the design of the study; the collection, analysis, and interpretation of the data; the writing of the manuscript; and the decision to submit the manuscript for publication.