The influence of obesity-related factors in the etiology of renal cell carcinoma-A mendelian randomization study
Language English Country United States Media electronic-ecollection
Document type Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't
Grant support
19169
Cancer Research UK - United Kingdom
MC_UU_12013/3
Medical Research Council - United Kingdom
CIHR - Canada
R01 CA170298
NCI NIH HHS - United States
202802/Z/16/Z
Wellcome Trust - United Kingdom
001
World Health Organization - International
MC_UU_12013/2
Medical Research Council - United Kingdom
C18281/A19169
Cancer Research UK - United Kingdom
U01 CA155309
NCI NIH HHS - United States
MC_UU_12013/1
Medical Research Council - United Kingdom
6858
Cancer Research UK - United Kingdom
MC_UU_00011/5
Medical Research Council - United Kingdom
RP-PG-0707-10101
Department of Health - United Kingdom
24390
Cancer Research UK - United Kingdom
PubMed
30605491
PubMed Central
PMC6317776
DOI
10.1371/journal.pmed.1002724
PII: PMEDICINE-D-18-01768
Knihovny.cz E-resources
- MeSH
- Genome-Wide Association Study MeSH
- Diabetes Mellitus, Type 2 complications MeSH
- Genetic Markers MeSH
- Body Mass Index MeSH
- Insulin blood MeSH
- Carcinoma, Renal Cell etiology genetics MeSH
- Blood Glucose analysis MeSH
- Blood Pressure MeSH
- Humans MeSH
- Lipids blood MeSH
- Mendelian Randomization Analysis MeSH
- Kidney Neoplasms etiology genetics MeSH
- Obesity complications genetics MeSH
- Risk Factors MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, N.I.H., Intramural MeSH
- Names of Substances
- Genetic Markers MeSH
- Insulin MeSH
- Blood Glucose MeSH
- Lipids MeSH
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.
American Cancer Society Atlanta Georgia United States of America
AP HP Department of Urology Hopitaux Universitaires Est Parisien Tenon Paris France
Brigham and Women's Hospital Harvard Medical School Boston Massachusetts United States of America
Brown University Providence Rhode Island United States of America
Cancer Epidemiology Centre Cancer Council Victoria Melbourne Australia
Cancer Science Institute of Singapore National University of Singapore Singapore Singapore
Carol Davila University of Medicine and Pharmacy Th Burghele Hospital Bucharest Romania
Clinic of Urology Clinical Center of Serbia Belgrade Serbia
CNRS UMR8200 Institute Gustave Roussy Villejuif France
College of Human Medicine Michigan State University Grand Rapids Michigan United States of America
Dana Farber Cancer Institute Boston Massachusetts United States of America
Department of Biobank Research Umeå University Umeå Sweden
Department of Cancer Epidemiology and Genetics Masaryk Memorial Cancer Institute Brno Czech Republic
Department of Community Medicine University of Tromsø The Arctic University of Norway Tromsø Norway
Department of Health Sciences Research Mayo Clinic Jacksonville Florida United States of America
Department of Medical Epidemiology and Biostatistics Karolinska Institutet Stockholm Sweden
Department of Medicine Brigham and Women's Hospital Boston Massachusetts United States of America
Department of Medicine Royal Melbourne Hospital University of Melbourne Melbourne Australia
Department of Oncology University of Cambridge Cambridge United Kingdom
Department of Preventive Medicine Faculty of Medicine Palacky University Olomouc Czech Republic
Department of Public Health and Primary Care University of Cambridge Cambridge United Kingdom
Department of Surgical and Perioperative Sciences Urology and Andrology Umeå University Umeå Sweden
Department of Surgical Sciences Uppsala University Uppsala Sweden
Department of Urology Mayo Clinic Rochester Minnesota United States of America
Diagnostics Program at Ferris State University Grand Rapids Michigan United States of America
Division of Urology Spectrum Health Grand Rapids Michigan United States of America
Fondation Jean Dausset Centre d'Etude du Polymorphisme Humain Paris France
Fred Hutchinson Cancer Research Center Seattle Washington United States of America
Genetic Epidemiology Group Folkhälsan Research Center Helsinki Finland
Harvard T H Chan School of Public Health Boston Massachusetts United States of America
Human Genetics Foundation Torino Italy
Imperial College London United Kingdom
Institute of Environmental Medicine Karolinska Institutet Stockholm Sweden
Institute of Molecular and Cell Biology A*STAR Singapore Singapore
Institute of Pathology Medical School of Belgrade Belgrade Serbia
International Agency for Research on Cancer Lyon France
International Organization for Cancer Prevention and Research Belgrade Serbia
Kurchatov Scientific Center Moscow Russian Federation
London School of Hygiene and Tropical Medicine University of London London United Kingdom
Max Planck Institute for Demographic Research Rostock Germany
Mayo Clinic Graduate School of Biomedical Sciences Rochester Minnesota United States of America
McGill University and Genome Quebec Innovation Centre Montreal Quebec Canada
MRC Integrative Epidemiology Unit University of Bristol Bristol United Kingdom
National Institute for Health and Welfare Helsinki Finland
National Institute of Public Health Bucharest Romania
National Public Health Center National Directorate of Environmental Health Budapest Hungary
QIMR Berghofer Medical Research Institute Herston Queensland Australia
Regional Authority of Public Health in Banska Bystrica Banska Bystrica Slovakia
Royal Marsden NHS Foundation Trust London United Kingdom
Russian N N Blokhin Cancer Research Centre Moscow Russian Federation
School of Public Health The University of Queensland Brisbane Australia
School of Social and Community Medicine University of Bristol Bristol United Kingdom
Spectrum Health Grand Rapids Michigan United States of America
St Jude Children's Research Hospital Memphis Tennessee United States of America
The Institute of Cancer Research London United Kingdom
The M Sklodowska Curie Cancer Center and Institute of Oncology Warsaw Poland
University of Cambridge Cambridge United Kingdom
UPMC Univ Paris 06 GRC n°5 Institut Universitaire de Cancérologie Paris France
Vanderbilt Ingram Cancer Center Nashville Tennessee United States of America
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