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Two susceptibility loci identified for prostate cancer aggressiveness.

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.

SUBMITTER: Berndt SI 

PROVIDER: S-EPMC4422072 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Two susceptibility loci identified for prostate cancer aggressiveness.

Berndt Sonja I SI   Wang Zhaoming Z   Yeager Meredith M   Alavanja Michael C MC   Albanes Demetrius D   Amundadottir Laufey L   Andriole Gerald G   Beane Freeman Laura L   Campa Daniele D   Cancel-Tassin Geraldine G   Canzian Federico F   Cornu Jean-Nicolas JN   Cussenot Olivier O   Diver W Ryan WR   Gapstur Susan M SM   Grönberg Henrik H   Haiman Christopher A CA   Henderson Brian B   Hutchinson Amy A   Hunter David J DJ   Key Timothy J TJ   Kolb Suzanne S   Koutros Stella S   Kraft Peter P   Le Marchand Loic L   Lindström Sara S   Machiela Mitchell J MJ   Ostrander Elaine A EA   Riboli Elio E   Schumacher Fred F   Siddiq Afshan A   Stanford Janet L JL   Stevens Victoria L VL   Travis Ruth C RC   Tsilidis Konstantinos K KK   Virtamo Jarmo J   Weinstein Stephanie S   Wilkund Fredrik F   Xu Jianfeng J   Lilly Zheng S S   Yu Kai K   Wheeler William W   Zhang Han H   Sampson Joshua J   Black Amanda A   Jacobs Kevin K   Hoover Robert N RN   Tucker Margaret M   Chanock Stephen J SJ  

Nature communications 20150505

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 a  ...[more]

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