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Two susceptibility loci identified for prostate cancer aggressiveness

2015; Nature Portfolio; Volume: 6; Issue: 1 Linguagem: Inglês

10.1038/ncomms7889

2041-1723

Sonja I. Berndt, Zhaoming Wang, Meredith Yeager, Michael C.R. Alavanja, Demetrius Albanes, Laufey T. Ámundadóttir, Gerald L. Andriole, Laura Beane Freeman, Daniele Campa, Géraldine Cancel‐Tassin, Federico Canzian, Jean‐Nicolas Cornu, Olivier Cussenot, W. Ryan Diver, Susan M. Gapstur, Henrik Grönberg, Christopher A. Haiman, Brian E. Henderson, Amy Hutchinson, David J. Hunter, Timothy J. Key, Suzanne Kolb, Stella Koutros, Peter Kraft, Loı̈c Le Marchand, Sara Lindström, Mitchell J. Machiela, Elaine A. Ostrander, Elio Ríboli, Fredrick R. Schumacher, Afshan Siddiq, Janet L. Stanford, Victoria L. Stevens, Ruth C. Travis, Konstantinos K. Tsilidis, Jarmo Virtamo, Stephanie J. Weinstein, Fredrik Wilkund, Jianfeng Xu, S. Lilly Zheng, Kai Yu, William Wheeler, Han Zhang, Sue A. Ingles, Rick A. Kittles, Sara S. Strom, Benjamin A. Rybicki, Barbara Nemesure, William B. Isaacs, Wei Zheng, Curtis A. Pettaway, Edward D. Yeboah, Yao Tettey, Richard Biritwum, Andrew A. Adjei, Evelyn Tay, Ann Truelove, Shelley Niwa, Anand P. Chokkalingam, Esther M. John, Adam B. Murphy, Lisa B. Signorello, John Carpten, M. Cristina Leske, Szu‐Yuan Wu, Anslem J. M. Hennis, Christine Neslund‐Dudas, Ann W. Hsing, Lisa W. Chu, Phyllis J. Goodman, Eric A. Klein, John S. Witte, Graham Casey, Sam Kaggwa, Michael B. Cook, Daniel O. Stram, William J. Blot, Joshua N. Sampson, Amanda Black, Kevin B. Jacobs, Robert N. Hoover, Margaret A. Tucker, Stephen J. Chanock,

Genetic Associations and Epidemiology

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.