| Literature DB >> 31231134 |
Ruhina S Laskar1, David C Muller2, Peng Li3, Mitchell J Machiela4, Yuanqing Ye5, Valerie Gaborieau1, Matthieu Foll1, Jonathan N Hofmann4, Leandro Colli4, Joshua N Sampson4, Zhaoming Wang6, Delphine Bacq-Daian7, Anne Boland7, Behnoush Abedi-Ardekani1, Geoffroy Durand1, Florence Le Calvez-Kelm1, Nivonirina Robinot1, Helene Blanche8, Egor Prokhortchouk9,10, Konstantin G Skryabin9,10, Laurie Burdett4, Meredith Yeager4, Sanja Radojevic-Skodric11, Slavisa Savic12, Lenka Foretova13, Ivana Holcatova14, Vladimir Janout15,16, Dana Mates17, Stefan Rascu18, Anush Mukeria19, David Zaridze19, Vladimir Bencko20, Cezary Cybulski21, Eleonora Fabianova22, Viorel Jinga18, Jolanta Lissowska23, Jan Lubinski21, Marie Navratilova13, Peter Rudnai24, Beata Świątkowska25, Simone Benhamou26,27, Geraldine Cancel-Tassin28,29, Olivier Cussenot28,29, Antonia Trichopoulou30, Elio Riboli2, Kim Overvad31, Salvatore Panico32, Borje Ljungberg33, Raviprakash T Sitaram33, Graham G Giles34,35, Roger L Milne34,35, Gianluca Severi34,36, Fiona Bruinsma34, Tony Fletcher37, Kvetoslava Koppova22, Susanna C Larsson38, Alicja Wolk38, Rosamonde E Banks39, Peter J Selby39, Douglas F Easton40,41, Paul Pharoah40,41, Gabriella Andreotti4, Laura E Beane Freeman4, Stella Koutros4, Demetrius Albanes4, Satu Männistö42, Stephanie Weinstein4, Peter E Clark43, Todd L Edwards43, Loren Lipworth43, Hallie Carol44, Matthew L Freedman44, Mark M Pomerantz44, Eunyoung Cho45, Peter Kraft46, Mark A Preston47, Kathryn M Wilson46, J Michael Gaziano47, Howard D Sesso46, Amanda Black4, Neal D Freedman4, Wen-Yi Huang4, John G Anema48, Richard J Kahnoski48, Brian R Lane48,49, Sabrina L Noyes50, David Petillo50, Bin Tean Teh50, Ulrike Peters51, Emily White51, Garnet L Anderson52, Lisa Johnson52, Juhua Luo53, Wong-Ho Chow5, Lee E Moore4, Toni K Choueiri44, Christopher Wood5, Mattias Johansson1, James D McKay1, Kevin M Brown4, Nathaniel Rothman4, Mark G Lathrop54, Jean-Francois Deleuze7,8, Xifeng Wu5, Paul Brennan1, Stephen J Chanock4, Mark P Purdue4, Ghislaine Scelo55.
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.Entities:
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Year: 2019 PMID： 31231134 PMCID： PMC6777615 DOI： 10.1038/s41431-019-0455-9
Source DB: PubMed Journal: Eur J Hum Genet ISSN： 1018-4813 Impact factor: 4.246