학술논문
Two susceptibility loci identified for prostate cancer aggressiveness.
Document Type
article
Author
Berndt, Sonja I; Wang, Zhaoming; Yeager, Meredith; Alavanja, Michael C; Albanes, Demetrius; Amundadottir, Laufey; Andriole, Gerald; Beane Freeman, Laura; Campa, Daniele; Cancel-Tassin, Geraldine; Canzian, Federico; Cornu, Jean-Nicolas; Cussenot, Olivier; Diver, W Ryan; Gapstur, Susan M; Grönberg, Henrik; Haiman, Christopher A; Henderson, Brian; Hutchinson, Amy; Hunter, David J; Key, Timothy J; Kolb, Suzanne; Koutros, Stella; Kraft, Peter; Le Marchand, Loic; Lindström, Sara; Machiela, Mitchell J; Ostrander, Elaine A; Riboli, Elio; Schumacher, Fred; Siddiq, Afshan; Stanford, Janet L; Stevens, Victoria L; Travis, Ruth C; Tsilidis, Konstantinos K; Virtamo, Jarmo; Weinstein, Stephanie; Wilkund, Fredrik; Xu, Jianfeng; Lilly Zheng, S; Yu, Kai; Wheeler, William; Zhang, Han; African Ancestry Prostate Cancer GWAS Consortium; Sampson, Joshua; Black, Amanda; Jacobs, Kevin; Hoover, Robert N; Tucker, Margaret; Chanock, Stephen J
Source
Nature communications. 6(1)
Subject
Language
Abstract
Most men diagnosed with prostate cancer will experience indolent disease; hence, discovering genetic variants that distinguish aggressive from nonaggressive prostate cancer is of critical clinical importance for disease prevention and treatment. In a multistage, case-only genome-wide association study of 12,518 prostate cancer cases, we identify two loci associated with Gleason score, a pathological measure of disease aggressiveness: rs35148638 at 5q14.3 (RASA1, P=6.49 × 10(-9)) and rs78943174 at 3q26.31 (NAALADL2, P=4.18 × 10(-8)). In a stratified case-control analysis, the SNP at 5q14.3 appears specific for aggressive prostate cancer (P=8.85 × 10(-5)) with no association for nonaggressive prostate cancer compared with controls (P=0.57). The proximity of these loci to genes involved in vascular disease suggests potential biological mechanisms worthy of further investigation.