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 x 10^-9) and rs78943174 at 3q26.31 (NAALADL2, P = 4.18 x 10^-8). In a stratified case–control analysis, the SNP at 5q14.3 appears specific for aggressive prostate cancer (P = 8.85 x 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.