Skip to Main Content

An official website of the United States government

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

About this Publication
Title
The influence of obesity-related factors in the etiology of renal cell carcinoma-A mendelian randomization study.
Pubmed ID
30605491 (View this publication on the PubMed website)
Publication
PLoS Med. 2019 Jan; Volume 16 (Issue 1): Pages e1002724
Authors
Johansson M, Carreras-Torres R, Scelo G, Purdue MP, Mariosa D, Muller DC, Timpson NJ, Haycock PC, Brown KM, Wang Z, Ye Y, Hofmann JN, Foll M, Gaborieau V, Machiela MJ, Colli LM, Li P, Garnier JG, Blanche H, Boland A, ...show more Burdette L, Prokhortchouk E, Skryabin KG, Yeager M, Radojevic-Skodric S, Ognjanovic S, Foretova L, Holcatova I, Janout V, Mates D, Mukeriya A, Rascu S, Zaridze D, Bencko V, Cybulski C, Fabianova E, Jinga V, Lissowska J, Lubinski J, Navratilova M, Rudnai P, Benhamou S, Cancel-Tassin G, Cussenot O, Weiderpass E, Ljungberg B, Tumkur Sitaram R, Häggström C, Bruinsma F, Jordan SJ, Severi G, Winship I, Hveem K, Vatten LJ, Fletcher T, Larsson SC, Wolk A, Banks RE, Selby PJ, Easton DF, Andreotti G, Beane Freeman LE, Koutros S, Männistö S, Weinstein S, Clark PE, Edwards TL, Lipworth L, Gapstur SM, Stevens VL, Carol H, Freedman ML, Pomerantz MM, Cho E, Wilson KM, Gaziano JM, Sesso HD, Freedman ND, Parker AS, Eckel-Passow JE, Huang WY, Kahnoski RJ, Lane BR, Noyes SL, Petillo D, Teh BT, Peters U, White E, Anderson GL, Johnson L, Luo J, Buring J, Lee IM, Chow WH, Moore LE, Eisen T, Henrion M, Larkin J, Barman P, Leibovich BC, Choueiri TK, Lathrop GM, Deleuze JF, Gunter M, McKay JD, Wu X, Houlston RS, Chanock SJ, Relton C, Richards JB, Martin RM, Davey Smith G, Brennan P
Affiliations
  • International Agency for Research on Cancer (IARC), Lyon, France.
  • Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department Health and Human Services, Bethesda, Maryland, United States of America.
  • Imperial College, London, United Kingdom.
  • MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.
  • St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America.
  • Department of Epidemiology, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
  • Centre National de Genotypage, Institut de Genomique, Centre de l'Energie Atomique et aux Energies Alternatives, Evry, France.
  • Fondation Jean Dausset - Centre d'Etude du Polymorphisme Humain, Paris, France.
  • Federal Research Centre "Fundamentals of Biotechnology" of the Russian Academy of Sciences, Moscow, Russian Federation.
  • Institute of Pathology, Medical School of Belgrade, Belgrade, Serbia.
...show more
  • Mayo Clinic Graduate School of Biomedical Sciences, Rochester, Minnesota, United States of America.
  • Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
  • Institute of Public Health and Preventive Medicine, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic.
  • Department of Preventive Medicine, Faculty of Medicine, Palacky University, Olomouc, Czech Republic.
  • National Institute of Public Health, Bucharest, Romania.
  • Russian N.N. Blokhin Cancer Research Centre, Moscow, Russian Federation.
  • Carol Davila University of Medicine and Pharmacy, Th. Burghele Hospital, Bucharest, Romania.
  • Institute of Hygiene and Epidemiology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic.
  • International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
  • Regional Authority of Public Health in Banska Bystrica, Banska Bystrica, Slovakia.
  • The M Sklodowska-Curie Cancer Center and Institute of Oncology, Warsaw, Poland.
  • National Public Health Center, National Directorate of Environmental Health, Budapest, Hungary.
  • INSERM U946, Paris, France.
  • CeRePP, Paris, France.
  • Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway.
  • Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden.
  • Department of Biobank Research, Umeå University, Umeå, Sweden.
  • Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia.
  • QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
  • "Health across generations" team, CESP Inserm, Facultés de Médicine Université Paris-Sud, UVSQ, Université Paris-Saclay, Gustave Roussy, Villejuif, France.
  • Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Melbourne, Australia.
  • K. G. Jebsen Center for Genetic Epidemiology, Department of Public Health, Norwegian University of Science and Technology, Trondheim, Norway.
  • Department of Public Health and General Practice, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
  • London School of Hygiene and Tropical Medicine, University of London, London, United Kingdom.
  • Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
  • Leeds Institute of Cancer and Pathology, University of Leeds, St James's University Hospital, Leeds, United Kingdom.
  • National Institute for Health Research Diagnostic Evidence Cooperative, Division of Surgery, Imperial College London, St Mary's Hospital, London, United Kingdom.
  • Department of Oncology, University of Cambridge, Cambridge, United Kingdom.
  • National Institute for Health and Welfare, Helsinki, Finland.
  • Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, United States of America.
  • Department of Medicine, Division of Epidemiology, Vanderbilt-Ingram Cancer Center, Vanderbilt Genetics Institute, Nashville, Tennessee, United States of America.
  • American Cancer Society, Atlanta, Georgia, United States of America.
  • Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.
  • Brown University, Providence, Rhode Island, United States of America.
  • Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America.
  • Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
  • Department of Health Sciences Research, Mayo Clinic, Jacksonville, Florida, United States of America.
  • Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, United States of America.
  • Division of Urology, Spectrum Health, Grand Rapids, Michigan, United States of America.
  • Van Andel Research Institute, Center for Cancer Genomics and Quantitative Biology, Grand Rapids, Michigan, United States of America.
  • Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
  • WHI Clinical Coordinating Center, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
  • Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
  • Department of Epidemiology and Biostatistics, School of Public Health Indiana University Bloomington, Bloomington, Indiana, United States of America.
  • University of Cambridge, Cambridge, United Kingdom.
  • The Institute of Cancer Research, London, United Kingdom.
  • Royal Marsden NHS Foundation Trust, London, United Kingdom.
  • Department of Urology, Mayo Clinic, Rochester, Minnesota, United States of America.
  • McGill University and Genome Quebec Innovation Centre, Montreal, Quebec, Canada.
  • Departments of Medicine, Human Genetics, Epidemiology and Biostatistics, Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
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 association study (GWAS) of 10,784 RCC patients and 20,406 control participants in a 2-sample MR framework. The effect on RCC risk was estimated by calculating odds ratios (ORSD) for a standard deviation (SD) increment in each risk factor. The MR analysis indicated that higher body mass index increases the risk of RCC (ORSD: 1.56, 95% confidence interval [CI] 1.44-1.70), with comparable results for waist-to-hip ratio (ORSD: 1.63, 95% CI 1.40-1.90) and body fat percentage (ORSD: 1.66, 95% CI 1.44-1.90). This analysis further indicated that higher fasting insulin (ORSD: 1.82, 95% CI 1.30-2.55) and diastolic blood pressure (DBP; ORSD: 1.28, 95% CI 1.11-1.47), but not systolic blood pressure (ORSD: 0.98, 95% CI 0.84-1.14), increase the risk for RCC. No association with RCC risk was seen for lipids, overall type 2 diabetes, or fasting glucose.

CONCLUSIONS: This study provides novel evidence for an etiological role of insulin in RCC, as well as confirmatory evidence that obesity and DBP influence RCC risk.

Related CDAS Studies
Related CDAS Projects