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

Authors:
Dr. Raviprakash Tumkur Sitaram, DVM, MVSc, PhD
Dr. Raviprakash Tumkur Sitaram, DVM, MVSc, PhD
Umeå University
Researcher
Cancer
Umeå, Vasterbotten | Sweden
Ruhina S Laskar David C Muller Peng Li Mitchell J Machiela Yuanqing Ye Valerie Gaborieau Matthieu Foll Jonathan N Hofmann Leandro Colli Joshua N Sampson Zhaoming Wang Delphine Bacq-Daian Anne Boland Behnoush Abedi-Ardekani Geoffroy Durand Florence Le Calvez-Kelm Nivonirina Robinot Helene Blanche Egor Prokhortchouk Konstantin G Skryabin Laurie Burdett Meredith Yeager Sanja Radojevic-Skodric Slavisa Savic Lenka Foretova Ivana Holcatova Vladimir Janout Dana Mates Stefan Rascu Anush Mukeria David Zaridze Vladimir Bencko Cezary Cybulski Eleonora Fabianova Viorel Jinga Jolanta Lissowska Jan Lubinski Marie Navratilova Peter Rudnai Beata Świątkowska Simone Benhamou Geraldine Cancel-Tassin Olivier Cussenot Antonia Trichopoulou Elio Riboli Kim Overvad Salvatore Panico Borje Ljungberg Raviprakash T Sitaram Graham G Giles Roger L Milne Gianluca Severi Fiona Bruinsma Tony Fletcher Kvetoslava Koppova Susanna C Larsson Alicja Wolk Rosamonde E Banks Peter J Selby Douglas F Easton Paul Pharoah Gabriella Andreotti Laura E Beane Freeman Stella Koutros Demetrius Albanes Satu Männistö Stephanie Weinstein Peter E Clark Todd L Edwards Loren Lipworth Hallie Carol Matthew L Freedman Mark M Pomerantz Eunyoung Cho Peter Kraft Mark A Preston Kathryn M Wilson J Michael Gaziano Howard D Sesso Amanda Black Neal D Freedman Wen-Yi Huang John G Anema 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 Wong-Ho Chow Lee E Moore Toni K Choueiri Christopher Wood Mattias Johansson James D McKay Kevin M Brown Nathaniel Rothman Mark G Lathrop Jean-Francois Deleuze Xifeng Wu Paul Brennan Stephen J Chanock Mark P Purdue Ghislaine Scelo

Eur J Hum Genet 2019 Oct 23;27(10):1589-1598. Epub 2019 Jun 23.

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

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 (OR) = 0.83 [95% CI = 0.78-0.89], P = 1.71 × 10 compared with female odds ratio (OR) = 0.98 [95% CI = 0.90-1.07], P = 0.68) and 12q23.3 (intergenic, OR = 0.75 [95% CI = 0.68-0.83], P = 1.59 × 10 compared with OR = 0.93 [95% CI = 0.82-1.06], P = 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.

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http://dx.doi.org/10.1038/s41431-019-0455-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6777615PMC
October 2019
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