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The influence of obesity-related factors in the etiology of renal cell carcinoma-A mendelian randomization study
M. Johansson, R. Carreras-Torres, G. Scelo, MP. Purdue, D. Mariosa, DC. Muller, NJ. Timpson, PC. Haycock, KM. Brown, Z. Wang, Y. Ye, JN. Hofmann, M. Foll, V. Gaborieau, MJ. Machiela, LM. Colli, P. Li, JG. Garnier, H. Blanche, A. Boland, L....
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, práce podpořená grantem
Grantová podpora
MC_UU_12013/1
Medical Research Council - United Kingdom
MC_UU_12013/2
Medical Research Council - United Kingdom
MC_UU_12013/3
Medical Research Council - United Kingdom
RP-PG-0707-10101
Department of Health - United Kingdom
C18281/A19169
Cancer Research UK - United Kingdom
U01 CA155309
NCI NIH HHS - United States
R01 CA170298
NCI NIH HHS - United States
Canadian Institutes of Health Research - International
NLK
Directory of Open Access Journals
od 2004
Free Medical Journals
od 2007
Public Library of Science (PLoS)
od 2004
Public Library of Science (PLoS)
od 2004
PubMed Central
od 2004
Europe PubMed Central
od 2004
ProQuest Central
od 2004-10-01
Open Access Digital Library
od 2004-10-01
Open Access Digital Library
od 2004-01-01
Open Access Digital Library
od 2004-10-01
Open Access Digital Library
od 2004-01-01
Medline Complete (EBSCOhost)
od 2004-10-01
Health & Medicine (ProQuest)
od 2004-10-01
ROAD: Directory of Open Access Scholarly Resources
od 2004
- MeSH
- celogenomová asociační studie MeSH
- diabetes mellitus 2. typu komplikace MeSH
- genetické markery MeSH
- index tělesné hmotnosti MeSH
- inzulin krev MeSH
- karcinom z renálních buněk etiologie genetika MeSH
- krevní glukóza analýza MeSH
- krevní tlak MeSH
- lidé MeSH
- lipidy krev MeSH
- mendelovská randomizace MeSH
- nádory ledvin etiologie genetika MeSH
- obezita komplikace genetika MeSH
- rizikové faktory MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, N.I.H., Intramural 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
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
Carol Davila University of Medicine and Pharmacy Th Burghele Hospital Bucharest Romania
CeRePP Paris France UPMC Univ Paris 06 GRC n°5 Institut Universitaire de Cancérologie Paris France
Dana Farber Cancer Institute Boston Massachusetts United States of America
Department of Cancer Epidemiology and Genetics Masaryk Memorial Cancer Institute Brno Czech Republic
Department of Health Sciences Research Mayo Clinic Jacksonville Florida United States of America
Department of Medicine Royal Melbourne Hospital University of Melbourne Melbourne Australia
Department of Preventive Medicine Faculty of Medicine Palacky University Olomouc Czech Republic
Department of Surgical and Perioperative Sciences Urology and Andrology Umeå University Umeå Sweden
Department of Urology Mayo Clinic Rochester Minnesota 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
Harvard T H Chan School of Public Health Boston Massachusetts United States of America
Imperial College London United Kingdom
INSERM U946 Paris France CNRS UMR8200 Institute Gustave Roussy Villejuif France
Institute of Environmental Medicine Karolinska Institutet Stockholm Sweden
International Agency for Research on Cancer Lyon France
London School of Hygiene and Tropical Medicine University of London London United Kingdom
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
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
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
Vanderbilt Ingram Cancer Center Nashville Tennessee United States of America
Citace poskytuje Crossref.org
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- $a The influence of obesity-related factors in the etiology of renal cell carcinoma-A mendelian randomization study / $c M. Johansson, R. Carreras-Torres, G. Scelo, MP. Purdue, D. Mariosa, DC. Muller, NJ. Timpson, PC. Haycock, KM. Brown, Z. Wang, Y. Ye, JN. Hofmann, M. Foll, V. Gaborieau, MJ. Machiela, LM. Colli, P. Li, JG. Garnier, H. Blanche, A. Boland, L. Burdette, E. Prokhortchouk, KG. Skryabin, M. Yeager, S. Radojevic-Skodric, S. Ognjanovic, L. Foretova, I. Holcatova, V. Janout, D. Mates, A. Mukeriya, S. Rascu, D. Zaridze, V. Bencko, C. Cybulski, E. Fabianova, V. Jinga, J. Lissowska, J. Lubinski, M. Navratilova, P. Rudnai, S. Benhamou, G. Cancel-Tassin, O. Cussenot, E. Weiderpass, B. Ljungberg, R. Tumkur Sitaram, C. Häggström, F. Bruinsma, SJ. Jordan, G. Severi, I. Winship, K. Hveem, LJ. Vatten, T. Fletcher, SC. Larsson, A. Wolk, RE. Banks, PJ. Selby, DF. Easton, G. Andreotti, LE. Beane Freeman, S. Koutros, S. Männistö, S. Weinstein, PE. Clark, TL. Edwards, L. Lipworth, SM. Gapstur, VL. Stevens, H. Carol, ML. Freedman, MM. Pomerantz, E. Cho, KM. Wilson, JM. Gaziano, HD. Sesso, ND. Freedman, AS. Parker, JE. Eckel-Passow, WY. Huang, RJ. Kahnoski, BR. Lane, SL. Noyes, D. Petillo, BT. Teh, U. Peters, E. White, GL. Anderson, L. Johnson, J. Luo, J. Buring, IM. Lee, WH. Chow, LE. Moore, T. Eisen, M. Henrion, J. Larkin, P. Barman, BC. Leibovich, TK. Choueiri, GM. Lathrop, JF. Deleuze, M. Gunter, JD. McKay, X. Wu, RS. Houlston, SJ. Chanock, C. Relton, JB. Richards, RM. Martin, G. Davey Smith, P. Brennan,
- 520 9_
- $a 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.
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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- 700 1_
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