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Eur J Hum Genet. 2019 Jun 23. doi: 10.1038/s41431-019-0455-9. [Epub ahead of print]

Sex specific associations in genome wide association analysis of renal cell carcinoma.

Author information

1
International Agency for Research on Cancer (IARC), Lyon, France.
2
Faculty of Medicine, School of Public Health, Imperial College London, London, UK.
3
Max Planck Institute for Demographic Research, Rostock, Germany.
4
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department Health and Human Services, Bethesda, MD, USA.
5
Department of Epidemiology, Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
6
Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, TN, USA.
7
Centre National de Recherche en Génomique Humaine, , Institut de biologie François Jacob, CEA, Evry, France.
8
Fondation Jean Dausset-Centre d'Etude du Polymorphisme Humain, Paris, France.
9
Center 'Bioengineering' of the Russian Academy of Sciences, Moscow, Russian Federation.
10
Kurchatov Scientific Center, Moscow, Russian Federation.
11
Institute of Pathology, Medical school of Belgrade, Belgrade, Serbia.
12
Department of Urology, University Hospital "Dr D. Misovic" Clinical Center, Belgrade, Serbia.
13
Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic.
14
2nd Faculty of Medicine, Institute of Public Health and Preventive Medicine, Charles University, Prague, Czech Republic.
15
Department of Preventive Medicine, Faculty of Medicine, Palacky University, Olomouc, Czech Republic.
16
Faculty of Health Sciences, Palacky University, Olomouc, Czech Republic.
17
National Institute of Public Health, Bucharest, Romania.
18
Carol Davila University of Medicine and Pharmacy, Th. Burghele Hospital, Bucharest, Romania.
19
Russian N.N. Blokhin Cancer Research Centre, Moscow, Russian Federation.
20
First Faculty of Medicine, Institute of Hygiene and Epidemiology, Charles University, Prague, Czech Republic.
21
International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
22
Regional Authority of Public Health in BanskaBystrica, BanskaBystrica, Slovakia.
23
The M Sklodowska-Curie Cancer Center and Institute of Oncology, Warsaw, Poland.
24
National Public Health Institute, Budapest, Hungary.
25
Department of Epidemiology, Nofer Institute of Occupational Medicine, Lodz, Poland.
26
INSERM U946, Paris, France.
27
CNRS UMR8200, Institute Gustave Roussy, Villejuif, France.
28
Sorbonne Université, GRC no. 5, ONCOTYPE-URO, AP-HP, Tenon Hospital, Paris, France.
29
CeRePP, Paris, France.
30
Hellenic Health Foundation, Alexandroupoleos 23, Athens, 11527, Greece.
31
Department of Public Health, Section for Epidemiology, Aarhus University, Aarhus C, Denmark.
32
Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy.
33
Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Umeå, Sweden.
34
Cancer Epidemiology & Intelligence Division, Cancer Council of Victoria, 615 St Kilda Road, Melbourne, VIC, 3004, Australia.
35
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville Victoria, 3010, Australia.
36
Inserm U1018, Center for Research in Epidemiology and Population Health (CESP), Facultés de Medicine, Université Paris-Saclay, Université Paris-Sud, UVSQ, Gustave Roussy, 114 rue Edouard Vaillant, 94805, Villejuif Cedex, France.
37
London School of Hygiene and Tropical Medicine, University of London, London, UK.
38
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
39
Leeds Institute of Cancer and Pathology, University of Leeds, Cancer Research Building, St James's University Hospital, Leeds, UK.
40
Department of Oncology, University of Cambridge, Cambridge, UK.
41
Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
42
National Institute for Health and Welfare, Helsinki, Finland.
43
Vanderbilt-Ingram Cancer Center, Nasville, TN, USA.
44
Dana-Farber Cancer Institute, Bostan, MA, USA.
45
Brown University, Providence, RI, USA.
46
Harvard T.H. Chan School of Public Health, Boston, MA, USA.
47
Brigham and Women's Hospital and VA Boston, Boston, MA, USA.
48
Division of Urology, Spectrum Health, Grand Rapids, MI, USA.
49
College of Human Medicine, Michigan State University, Grand Rapids, MI, USA.
50
Van Andel Research Institute, Center for Cancer Genomics and Quantitative Biology, Grand Rapids, MI, USA.
51
Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
52
Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
53
Department of Epidemiology and Biostatistics, School of Public Health Indiana University Bloomington, Bloomington, IN, USA.
54
McGill University and Genome Quebec Innovation Centre, Montreal, Quebec, Canada.
55
International Agency for Research on Cancer (IARC), Lyon, France. scelog@iarc.fr.

Abstract

Renal cell carcinoma (RCC) has an undisputed genetic component and a stable 2:1 male to female sex ratio in its incidence across populations, suggesting possible sexual dimorphism in its genetic susceptibility. We conducted the first sex-specific genome-wide association analysis of RCC for men (3227 cases, 4916 controls) and women (1992 cases, 3095 controls) of European ancestry from two RCC genome-wide scans and replicated the top findings using an additional series of men (2261 cases, 5852 controls) and women (1399 cases, 1575 controls) from two independent cohorts of European origin. Our study confirmed sex-specific associations for two known RCC risk loci at 14q24.2 (DPF3) and 2p21(EPAS1). We also identified two additional suggestive male-specific loci at 6q24.3 (SAMD5, male odds ratio (ORmale) = 0.83 [95% CI = 0.78-0.89], Pmale = 1.71 × 10-8 compared with female odds ratio (ORfemale) = 0.98 [95% CI = 0.90-1.07], Pfemale = 0.68) and 12q23.3 (intergenic, ORmale = 0.75 [95% CI = 0.68-0.83], Pmale = 1.59 × 10-8 compared with ORfemale = 0.93 [95% CI = 0.82-1.06], Pfemale = 0.21) that attained genome-wide significance in the joint meta-analysis. Herein, we provide evidence of sex-specific associations in RCC genetic susceptibility and advocate the necessity of larger genetic and genomic studies to unravel the endogenous causes of sex bias in sexually dimorphic traits and diseases like RCC.

PMID:
31231134
DOI:
10.1038/s41431-019-0455-9

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