Two susceptibility loci identified for prostate cancer aggressiveness

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. Prostate cancer often does not progress to invasive disease and thus markers predicting the course of the disease progression are critical for optimal treatment choices. Here the authors show that variants at two genetic loci correlate with the aggressiveness of prostate cancer.