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

Authors:
Dr. Raviprakash Tumkur Sitaram, DVM, MVSc, PhD
Dr. Raviprakash Tumkur Sitaram, DVM, MVSc, PhD
Umeå University
Researcher
Cancer
Umeå, Vasterbotten | Sweden
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 Laurie Burdette Egor Prokhortchouk Konstantin G Skryabin Meredith Yeager Sanja Radojevic-Skodric Simona Ognjanovic Lenka Foretova Ivana Holcatova Vladimir Janout Dana Mates Anush Mukeriya Stefan Rascu David Zaridze Vladimir Bencko Cezary Cybulski Eleonora Fabianova Viorel Jinga Jolanta Lissowska Jan Lubinski Marie Navratilova Peter Rudnai Simone Benhamou Geraldine Cancel-Tassin Olivier Cussenot Elisabete Weiderpass Börje Ljungberg Christel Häggström Fiona Bruinsma Susan J Jordan Gianluca Severi Ingrid Winship Kristian Hveem Lars J Vatten Tony Fletcher Susanna C Larsson Alicja Wolk Rosamonde E Banks Peter J Selby Douglas F Easton Gabriella Andreotti Laura E Beane Freeman Stella Koutros Satu Männistö Stephanie Weinstein Peter E Clark Todd L Edwards Loren Lipworth Susan M Gapstur Victoria L Stevens Hallie Carol Matthew L Freedman Mark M Pomerantz Eunyoung Cho Kathryn M Wilson J Michael Gaziano Howard D Sesso Neal D Freedman Alexander S Parker Jeanette E Eckel-Passow Wen-Yi Huang Richard J Kahnoski Brian R Lane Sabrina L Noyes David Petillo Bin Tean Teh Ulrike Peters Emily White Garnet L Anderson Lisa Johnson Juhua Luo Julie Buring I-Min Lee Wong-Ho Chow Lee E Moore Timothy Eisen Marc Henrion James Larkin Poulami Barman Bradley C Leibovich Toni K Choueiri G Mark Lathrop Jean-Francois Deleuze Marc Gunter James D McKay Xifeng Wu Richard S Houlston Stephen J Chanock Caroline Relton J Brent Richards Richard M Martin George Davey Smith Paul Brennan

PLoS Med 2019 01 3;16(1):e1002724. Epub 2019 Jan 3.

International Agency for Research on Cancer (IARC), Lyon, France.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pmed.1002724DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317776PMC
January 2019
62 Reads

Publication Analysis

Top Keywords

rcc risk
20
blood pressure
12
risk
10
rcc
10
lipids type
8
genetic markers
8
risk rcc
8
obesity-related factors
8
analysis indicated
8
indicated higher
8
mendelian randomization
8
type diabetes
8
association rcc
8
renal cell
8
orsd
7
95%
6
mass increases
4
increases risk
4
body mass
4
risk subsequently
4

Similar Publications