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Nat Commun. 2017 Jun 9;8:15724. doi: 10.1038/ncomms15724.

Genome-wide association study identifies multiple risk loci for renal cell carcinoma.

Scelo G1, Purdue MP2, Brown KM2, Johansson M1, Wang Z3, Eckel-Passow JE4, Ye Y5, Hofmann JN2, Choi J2, Foll M1, Gaborieau V1, Machiela MJ2, Colli LM2, Li P1, Sampson JN2, Abedi-Ardekani B1, Besse C6, Blanche H7, Boland A6, Burdette L2, Chabrier A1, Durand G1, Le Calvez-Kelm F1, Prokhortchouk E8,9, Robinot N1, Skryabin KG8,9, Wozniak MB1, Yeager M2, Basta-Jovanovic G10, Dzamic Z11, Foretova L12, Holcatova I13, Janout V14, Mates D15, Mukeriya A16, Rascu S17, Zaridze D16, Bencko V18, Cybulski C19, Fabianova E20, Jinga V17, Lissowska J21, Lubinski J19, Navratilova M12, Rudnai P22, Szeszenia-Dabrowska N23, Benhamou S24, Cancel-Tassin G25,26, Cussenot O25,26, Baglietto L27, Boeing H28, Khaw KT29, Weiderpass E30,31,32,33, Ljungberg B34, Sitaram RT34, Bruinsma F35, Jordan SJ36,37, Severi G27,35,38,39, Winship I40,41, Hveem K42, Vatten LJ43, Fletcher T44, Koppova K20, Larsson SC45, Wolk A45, Banks RE46, Selby PJ46, Easton DF29,47, Pharoah P29,47, Andreotti G2, Freeman LEB2, Koutros S2, Albanes D2, Männistö S48, Weinstein S2, Clark PE49, Edwards TL50, Lipworth L51, Gapstur SM52, Stevens VL52, Carol H53, Freedman ML53, Pomerantz MM53, Cho E54, Kraft P55, Preston MA56, Wilson KM55, Michael Gaziano J56, Sesso HD55,56, Black A2, Freedman ND2, Huang WY2, Anema JG57, Kahnoski RJ57, Lane BR57,58, Noyes SL59, Petillo D59, Teh BT59, Peters U60, White E60, Anderson GL60, Johnson L60, Luo J61, Buring J55,56, Lee IM55,56, Chow WH5, Moore LE2, Wood C62, Eisen T63, Henrion M64, Larkin J65, Barman P4, Leibovich BC66, Choueiri TK53, Mark Lathrop G67, Rothman N2, Deleuze JF6,7, McKay JD1, Parker AS68, Wu X5, Houlston RS69,70, Brennan P1, Chanock SJ2.

Author information

1
International Agency for Research on Cancer (IARC), 69008 Lyon, France.
2
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department Health and Human Services, Bethesda, Maryland 20892, USA.
3
Department of Computational Biology, St Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
4
Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota 55905, USA.
5
Department of Epidemiology, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, Texas 77230, USA.
6
Centre National de Genotypage, Institut de Genomique, Commissariat à l'Energie Atomique et aux Energies Alternatives, 91057 Evry, France.
7
Fondation Jean Dausset-Centre d'Etude du Polymorphisme Humain, 75010 Paris, France.
8
Center 'Bioengineering' of the Russian Academy of Sciences, Moscow 117312, Russia.
9
Kurchatov Scientific Center, Moscow 123182, Russia.
10
Institute of Pathology, School of Medicine, University of Belgrade, 11000 Belgrade, Serbia.
11
Clinical Center of Serbia (KCS), Clinic of Urology, University of Belgrade-Faculty of Medicine, 11000 Belgrade, Serbia.
12
Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, 656 53 Brno, Czech Republic.
13
2nd Faculty of Medicine, Institute of Public Health and Preventive Medicine, Charles University, 150 06 Prague 5, Czech Republic.
14
Department of Preventive Medicine, Faculty of Medicine, Palacky University, 775 15 Olomouc, Czech Republic.
15
National Institute of Public Health, 050463 Bucharest, Romania.
16
Russian N.N. Blokhin Cancer Research Centre, Moscow 115478, Russian Federation.
17
Carol Davila University of Medicine and Pharmacy, Th. Burghele Hospital, 050659 Bucharest, Romania.
18
First Faculty of Medicine, Institute of Hygiene and Epidemiology, Charles University, 128 00 Prague 2, Czech Republic.
19
International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, 70-204 Szczecin, Poland.
20
Regional Authority of Public Health in Banska Bystrica, 975 56 Banska Bystrica, Slovakia.
21
The M Sklodowska-Curie Cancer Center and Institute of Oncology, 02-034 Warsaw, Poland.
22
National Public Health Center, National Directorate of Environmental Health, 1097 Budapest, Hungary.
23
Department of Epidemiology, Institute of Occupational Medicine, 91-348 Lodz, Poland.
24
Université Paris Diderot, INSERM, Unité Variabilité Génétique et Maladies Humaines, 75010 Paris, France.
25
CeRePP, Tenon Hospital, 75020 Paris, France.
26
UPMC Univ Paris 06 GRC n°5, 75013 Paris, France.
27
Centre de Recherche en Épidémiologie et Santé des Populations (CESP, Inserm U1018), Université Paris-Saclay, UPS, UVSQ, Gustave Roussy, 94805 Villejuif, France.
28
Department of Epidemiology, German Institute of Human Nutrition (DIfE) Potsdam-Rehbrücke, 14558 Nuthetal, Germany.
29
Department of Public Health and Primary Care, University of Cambridge, Cambridge CB2 0QQ, UK.
30
Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, 9037 Tromsø, Norway.
31
Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, 0304 Oslo, Norway.
32
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 77 Stockholm, Sweden.
33
Genetic Epidemiology Group, Folkhälsan Research Center, 00250 Helsinki, Finland.
34
Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, 901 85 Umeå, Sweden.
35
Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria 3004, Australia.
36
QIMR Berghofer Medical Research Institute, Herston, Queensland 4006, Australia.
37
School of Public Health, The University of Queensland, Brisbane, Queensland 4072, Australia.
38
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Carlton, Victoria 3053, Australia.
39
Human Genetics Foundation (HuGeF), 10126 Torino, Italy.
40
Department of Medicine, The University of Melbourne, Melbourne, Victoria 3010, Australia.
41
Genetic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia.
42
HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger 7600, Norway.
43
Department of Public Health and General Practice, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim 7491, Norway.
44
London School of Hygiene and Tropical Medicine, University of London, London WC1H 9SH, UK.
45
Institute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm, Sweden.
46
Leeds Institute of Cancer and Pathology, University of Leeds, Cancer Research Building, St James's University Hospital, Leeds LS9 7TF, UK.
47
Department of Oncology, University of Cambridge, Cambridge CB1 8RN, UK.
48
Department of Health, National Institute for Health and Welfare, 00271 Helsinki, Finland.
49
Vanderbilt-Ingram Cancer Center, Department of Urology, Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
50
Vanderbilt-Ingram Cancer Center, Division of Epidemiology, Department of Medicine, Institute for Medicine and Public Health, Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, Tennessee 37209, USA.
51
Vanderbilt-Ingram Cancer Center, Division of Epidemiology, Department of Medicine, Institute for Medicine and Public Health, Vanderbilt University Medical Center, Nashville, Tennessee 37203, USA.
52
American Cancer Society, Atlanta, Georgia 30303, USA.
53
Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.
54
Warren Alpert Medical School of Brown University, Providence, Rhode Island 02903, USA.
55
Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115, USA.
56
Brigham and Women's Hospital and VA Boston, Boston, Massachusetts 02115, USA.
57
Division of Urology, Spectrum Health, Grand Rapids, Michigan 49503, USA.
58
College of Human Medicine, Michigan State University, Grand Rapids, Michigan 49503, USA.
59
Van Andel Research Institute, Center for Cancer Genomics and Quantitative Biology, Grand Rapids, Michigan 49503, USA.
60
Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
61
Department of Epidemiology and Biostatistics, School of Public Health Indiana University Bloomington, Bloomington, Indiana 47405, USA.
62
Department of Urology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
63
Department of Oncology, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, UK.
64
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
65
Medical Oncology, Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK.
66
Department of Urology, Mayo Medical School and Mayo Clinic, Rochester, Minnesota 55902, USA.
67
McGill University and Genome Quebec Innovation Centre, Montreal, Quebec, Canada H3A 0G1.
68
Department of Health Sciences Research, Mayo Clinic, Jacksonville, Florida 32224, USA.
69
Division of Genetics and Epidemiology, The Institute of Cancer Research, London SW7 3RP, UK.
70
Division of Molecular Pathology, The Institute of Cancer Research, London SW7 3RP, UK.

Abstract

Previous genome-wide association studies (GWAS) have identified six risk loci for renal cell carcinoma (RCC). We conducted a meta-analysis of two new scans of 5,198 cases and 7,331 controls together with four existing scans, totalling 10,784 cases and 20,406 controls of European ancestry. Twenty-four loci were tested in an additional 3,182 cases and 6,301 controls. We confirm the six known RCC risk loci and identify seven new loci at 1p32.3 (rs4381241, P=3.1 × 10-10), 3p22.1 (rs67311347, P=2.5 × 10-8), 3q26.2 (rs10936602, P=8.8 × 10-9), 8p21.3 (rs2241261, P=5.8 × 10-9), 10q24.33-q25.1 (rs11813268, P=3.9 × 10-8), 11q22.3 (rs74911261, P=2.1 × 10-10) and 14q24.2 (rs4903064, P=2.2 × 10-24). Expression quantitative trait analyses suggest plausible candidate genes at these regions that may contribute to RCC susceptibility.

PMID:
28598434
PMCID:
PMC5472706
DOI:
10.1038/ncomms15724
[Indexed for MEDLINE]
Free PMC Article

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