Two susceptibility loci identified for prostate cancer aggressiveness
Menée sur 12 518 patients atteints d'un cancer de la prostate, cette étude identifie un polymorphisme à simple nucléotide situé sur la région chromosomique 5q14.3 en association avec un risque d'une forme agressive de la maladie
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 [times] 10-9) and rs78943174 at 3q26.31 (NAALADL2, P=4.18 [times] 10-8). In a stratified case-control analysis, the SNP at 5q14.3 appears specific for aggressive prostate cancer (P=8.85 [times] 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.