Two susceptibility loci identified for prostate cancer aggressiveness.
Berndt SI., Wang Z., Yeager M., Alavanja MC., Albanes D., Amundadottir L., Andriole G., Beane Freeman L., Campa D., Cancel-Tassin G., Canzian F., Cornu JN., Cussenot O., Diver WR., Gapstur SM., Grönberg H., Haiman CA., Henderson B., Hutchinson A., Hunter DJ., Key TJ., Kolb S., Koutros S., Kraft P., Le Marchand L., Lindström S., Machiela MJ., Ostrander EA., Riboli E., Schumacher F., Siddiq A., Stanford JL., Stevens VL., Travis RC., Tsilidis KK., Virtamo J., Weinstein S., Wilkund F., Xu J., Lilly Zheng S., Yu K., Wheeler W., Zhang H., African Ancestry Prostate Cancer GWAS Consortium None., Sampson J., Black A., Jacobs K., Hoover RN., Tucker M., Chanock SJ.
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.