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Two susceptibility loci identified for prostate cancer aggressiveness.

  • Author(s): Berndt, Sonja I;
  • Wang, Zhaoming;
  • Yeager, Meredith;
  • Alavanja, Michael C;
  • Albanes, Demetrius;
  • Amundadottir, Laufey;
  • Andriole, Gerald;
  • Beane Freeman, Laura;
  • Campa, Daniele;
  • Cancel-Tassin, Geraldine;
  • Canzian, Federico;
  • Cornu, Jean-Nicolas;
  • Cussenot, Olivier;
  • Diver, W Ryan;
  • Gapstur, Susan M;
  • Grönberg, Henrik;
  • Haiman, Christopher A;
  • Henderson, Brian;
  • Hutchinson, Amy;
  • Hunter, David J;
  • Key, Timothy J;
  • Kolb, Suzanne;
  • Koutros, Stella;
  • Kraft, Peter;
  • Le Marchand, Loic;
  • Lindström, Sara;
  • Machiela, Mitchell J;
  • Ostrander, Elaine A;
  • Riboli, Elio;
  • Schumacher, Fred;
  • Siddiq, Afshan;
  • Stanford, Janet L;
  • Stevens, Victoria L;
  • Travis, Ruth C;
  • Tsilidis, Konstantinos K;
  • Virtamo, Jarmo;
  • Weinstein, Stephanie;
  • Wilkund, Fredrik;
  • Xu, Jianfeng;
  • Lilly Zheng, S;
  • Yu, Kai;
  • Wheeler, William;
  • Zhang, Han;
  • African Ancestry Prostate Cancer GWAS Consortium;
  • Sampson, Joshua;
  • Black, Amanda;
  • Jacobs, Kevin;
  • Hoover, Robert N;
  • Tucker, Margaret;
  • Chanock, Stephen J
  • et al.
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.

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