Format

Send to

Choose Destination

See 1 citation found by title matching your search:

PLoS Med. 2019 Jan 3;16(1):e1002724. doi: 10.1371/journal.pmed.1002724. eCollection 2019 Jan.

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

Johansson M1, Carreras-Torres R1, Scelo G1, Purdue MP2, Mariosa D1, Muller DC3, Timpson NJ4, Haycock PC4, Brown KM2, Wang Z5, Ye Y6, Hofmann JN2, Foll M1, Gaborieau V1, Machiela MJ2, Colli LM2, Li P1,7, Garnier JG8,9, Blanche H9, Boland A8, Burdette L2, Prokhortchouk E10, Skryabin KG10,11, Yeager M2, Radojevic-Skodric S12,13, Ognjanovic S14,15, Foretova L16, Holcatova I17, Janout V18, Mates D19, Mukeriya A20, Rascu S21, Zaridze D20, Bencko V22, Cybulski C23, Fabianova E24, Jinga V21, Lissowska J25, Lubinski J23, Navratilova M16, Rudnai P26, Benhamou S27,28, Cancel-Tassin G29,30, Cussenot O29,30,31, Weiderpass E32,33,34,35, Ljungberg B36, Tumkur Sitaram R36, Häggström C37,38, Bruinsma F39, Jordan SJ40,41, Severi G42,43, Winship I44, Hveem K45, Vatten LJ46, Fletcher T47, Larsson SC48, Wolk A48, Banks RE49, Selby PJ50, Easton DF51,52, Andreotti G2, Beane Freeman LE2, Koutros S2, Männistö S53, Weinstein S2, Clark PE54, Edwards TL55, Lipworth L54, Gapstur SM56, Stevens VL56, Carol H57, Freedman ML57, Pomerantz MM57, Cho E58, Wilson KM59, Gaziano JM60, Sesso HD59,61, Freedman ND2, Parker AS62, Eckel-Passow JE63, Huang WY2, Kahnoski RJ64, Lane BR64,65, Noyes SL66,67, Petillo D66,68, Teh BT66,69,70,71,72, Peters U73, White E73, Anderson GL74, Johnson L75, Luo J76, Buring J60,61, Lee IM60,61, Chow WH6, Moore LE2, Eisen T77, Henrion M78,79, Larkin J80, Barman P63, Leibovich BC81, Choueiri TK57, Lathrop GM82, Deleuze JF8,9, Gunter M1, McKay JD1, Wu X6, Houlston RS78, Chanock SJ2, Relton C4,83, Richards JB84, Martin RM4,83,85, Davey Smith G4,83, Brennan P1.

Author information

1
International Agency for Research on Cancer (IARC), Lyon, France.
2
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department Health and Human Services, Bethesda, Maryland, United States of America.
3
Imperial College, London, United Kingdom.
4
MRC Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.
5
St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America.
6
Department of Epidemiology, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
7
Max Planck Institute for Demographic Research, Rostock, Germany.
8
Centre National de Genotypage, Institut de Genomique, Centre de l'Energie Atomique et aux Energies Alternatives, Evry, France.
9
Fondation Jean Dausset - Centre d'Etude du Polymorphisme Humain, Paris, France.
10
Federal Research Centre "Fundamentals of Biotechnology" of the Russian Academy of Sciences, Moscow, Russian Federation.
11
Kurchatov Scientific Center, Moscow, Russian Federation.
12
Institute of Pathology, Medical School of Belgrade, Belgrade, Serbia.
13
Clinic of Urology, Clinical Center of Serbia, Belgrade, Serbia.
14
Mayo Clinic Graduate School of Biomedical Sciences, Rochester, Minnesota, United States of America.
15
International Organization for Cancer Prevention and Research (IOCPR), Belgrade, Serbia.
16
Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
17
Institute of Public Health and Preventive Medicine, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic.
18
Department of Preventive Medicine, Faculty of Medicine, Palacky University, Olomouc, Czech Republic.
19
National Institute of Public Health, Bucharest, Romania.
20
Russian N.N. Blokhin Cancer Research Centre, Moscow, Russian Federation.
21
Carol Davila University of Medicine and Pharmacy, Th. Burghele Hospital, Bucharest, Romania.
22
Institute of Hygiene and Epidemiology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic.
23
International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
24
Regional Authority of Public Health in Banska Bystrica, Banska Bystrica, Slovakia.
25
The M Sklodowska-Curie Cancer Center and Institute of Oncology, Warsaw, Poland.
26
National Public Health Center, National Directorate of Environmental Health, Budapest, Hungary.
27
INSERM U946, Paris, France.
28
CNRS UMR8200, Institute Gustave Roussy, Villejuif, France.
29
CeRePP, Paris, France.
30
UPMC Univ Paris 06, GRC n°5, Institut Universitaire de Cancérologie, Paris, France.
31
AP-HP, Department of Urology, Hopitaux Universitaires Est Parisien Tenon, Paris, France.
32
Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway.
33
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
34
Genetic Epidemiology Group, Folkhälsan Research Center, Helsinki, Finland.
35
Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway.
36
Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden.
37
Department of Biobank Research, Umeå University, Umeå, Sweden.
38
Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
39
Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Australia.
40
QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
41
School of Public Health, The University of Queensland, Brisbane, Australia.
42
"Health across generations" team, CESP Inserm, Facultés de Médicine Université Paris-Sud, UVSQ, Université Paris-Saclay, Gustave Roussy, Villejuif, France.
43
Human Genetics Foundation (HuGeF), Torino, Italy.
44
Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Melbourne, Australia.
45
K. G. Jebsen Center for Genetic Epidemiology, Department of Public Health, Norwegian University of Science and Technology, Trondheim, Norway.
46
Department of Public Health and General Practice, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
47
London School of Hygiene and Tropical Medicine, University of London, London, United Kingdom.
48
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
49
Leeds Institute of Cancer and Pathology, University of Leeds, St James's University Hospital, Leeds, United Kingdom.
50
National Institute for Health Research Diagnostic Evidence Cooperative, Division of Surgery, Imperial College London, St Mary's Hospital, London, United Kingdom.
51
Department of Oncology, University of Cambridge, Cambridge, United Kingdom.
52
Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
53
National Institute for Health and Welfare, Helsinki, Finland.
54
Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, United States of America.
55
Department of Medicine, Division of Epidemiology, Vanderbilt-Ingram Cancer Center, Vanderbilt Genetics Institute, Nashville, Tennessee, United States of America.
56
American Cancer Society, Atlanta, Georgia, United States of America.
57
Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.
58
Brown University, Providence, Rhode Island, United States of America.
59
Harvard T.H. Chan School of Public Health, Boston, Massachusetts, United States of America.
60
Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
61
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.
62
Department of Health Sciences Research, Mayo Clinic, Jacksonville, Florida, United States of America.
63
Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota, United States of America.
64
Division of Urology, Spectrum Health, Grand Rapids, Michigan, United States of America.
65
College of Human Medicine, Michigan State University, Grand Rapids, Michigan, United States of America.
66
Van Andel Research Institute, Center for Cancer Genomics and Quantitative Biology, Grand Rapids, Michigan, United States of America.
67
Spectrum Health, Grand Rapids, Michigan, United States of America.
68
Diagnostics Program at Ferris State University, Grand Rapids, Michigan, United States of America.
69
Program in Cancer and Stem Cell Biology, Duke-National, University of Singapore Medical School, Singapore, Singapore.
70
Institute of Molecular and Cell Biology, A*STAR, Singapore, Singapore.
71
Laboratory of Cancer Epigenome, Division of Medical Sciences, National Cancer Centre Singapore, Singapore, Singapore.
72
Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
73
Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
74
WHI Clinical Coordinating Center, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
75
Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
76
Department of Epidemiology and Biostatistics, School of Public Health Indiana University Bloomington, Bloomington, Indiana, United States of America.
77
University of Cambridge, Cambridge, United Kingdom.
78
The Institute of Cancer Research, London, United Kingdom.
79
Dept. of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
80
Royal Marsden NHS Foundation Trust, London, United Kingdom.
81
Department of Urology, Mayo Clinic, Rochester, Minnesota, United States of America.
82
McGill University and Genome Quebec Innovation Centre, Montreal, Quebec, Canada.
83
School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
84
Departments of Medicine, Human Genetics, Epidemiology and Biostatistics, Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
85
University Hospitals Bristol NHS Foundation Trust National Institute for Health Research Bristol Nutrition Biomedical Research Unit, University of Bristol, Bristol, United Kingdom.

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.

Conflict of interest statement

I have read the journal's policy and the authors of this manuscript have the following competing interests: TE declared employment, research support, and stock in AstraZeneca and research support from Bayer and Pfizer. PCH is a population health fellow of Cancer Research UK. GDS is a member of the Editorial Board of PLOS Medicine.

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center