Two susceptibility loci identified for prostate cancer aggressiveness

Sonja I. Berndt (), Zhaoming Wang, Meredith Yeager, Michael C. Alavanja, Demetrius Albanes, Laufey Amundadottir, Gerald Andriole, Laura Beane Freeman, Daniele Campa, Geraldine Cancel-Tassin, Federico Canzian, Jean-Nicolas Cornu, Olivier Cussenot, W. Ryan Diver, Susan M. Gapstur, Henrik Grönberg, Christopher A. Haiman, Brian Henderson, Amy Hutchinson, David J. Hunter, Timothy J. Key, Suzanne Kolb, Stella Koutros, Peter Kraft, Loic Le Marchand, Sara Lindström, Mitchell J. Machiela, Elaine A. Ostrander, Elio Riboli, Fred Schumacher, Afshan Siddiq, Janet L. Stanford, Victoria L. Stevens, Ruth C. Travis, Konstantinos K. Tsilidis, Jarmo Virtamo, Stephanie Weinstein, Fredrik Wilkund, Jianfeng Xu, S. Lilly Zheng, Kai Yu, William Wheeler, Han Zhang, Joshua Sampson, Amanda Black, Kevin Jacobs, Robert N. Hoover, Margaret Tucker and Stephen J. Chanock
Additional contact information
Sonja I. Berndt: National Cancer Institute
Zhaoming Wang: National Cancer Institute
Meredith Yeager: National Cancer Institute
Michael C. Alavanja: National Cancer Institute
Demetrius Albanes: National Cancer Institute
Laufey Amundadottir: National Cancer Institute
Gerald Andriole: Washington University School of Medicine
Laura Beane Freeman: National Cancer Institute
Daniele Campa: German Cancer Research Center (DKFZ)
Geraldine Cancel-Tassin: CeRePP, Assistance Publique-Hôpitaux de Paris, UPMC University Paris 6
Federico Canzian: Genomic Epidemiology Group, German Cancer Research Center (DKFZ)
Jean-Nicolas Cornu: National Cancer Institute
Olivier Cussenot: CeRePP, Assistance Publique-Hôpitaux de Paris, UPMC University Paris 6
W. Ryan Diver: Epidemiology Research Program, American Cancer Society
Susan M. Gapstur: Epidemiology Research Program, American Cancer Society
Henrik Grönberg: Karolinska Institute
Christopher A. Haiman: Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center
Brian Henderson: Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center
Amy Hutchinson: Cancer Genomics Research Laboratory, National Cancer Institute, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research
David J. Hunter: Harvard School of Public Health
Timothy J. Key: Cancer Epidemiology Unit, University of Oxford
Suzanne Kolb: Fred Hutchinson Cancer Research Center
Stella Koutros: National Cancer Institute
Peter Kraft: Harvard School of Public Health
Loic Le Marchand: Epidemiology Program, University of Hawaii Cancer Center
Sara Lindström: Harvard School of Public Health
Mitchell J. Machiela: National Cancer Institute
Elaine A. Ostrander: National Human Genome Research Institute, National Institutes of Health
Elio Riboli: School of Public Health, Imperial College
Fred Schumacher: Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center
Afshan Siddiq: School of Public Health, Imperial College London
Janet L. Stanford: Fred Hutchinson Cancer Research Center
Victoria L. Stevens: Epidemiology Research Program, American Cancer Society
Ruth C. Travis: Cancer Epidemiology Unit, University of Oxford
Konstantinos K. Tsilidis: University of Ioannina School of Medicine
Jarmo Virtamo: National Institute for Health and Welfare
Stephanie Weinstein: National Cancer Institute
Fredrik Wilkund: Karolinska Institute
Jianfeng Xu: Center for Cancer Genomics, Wake Forest University School of Medicine
S. Lilly Zheng: Center for Cancer Genomics, Wake Forest University School of Medicine
Kai Yu: National Cancer Institute
William Wheeler: Information Management Services Inc.
Han Zhang: National Cancer Institute
Joshua Sampson: National Cancer Institute
Amanda Black: National Cancer Institute
Kevin Jacobs: National Cancer Institute
Robert N. Hoover: National Cancer Institute
Margaret Tucker: National Cancer Institute
Stephen J. Chanock: National Cancer Institute

Nature Communications, 2015, vol. 6, issue 1, 1-7

Abstract: 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.

Date: 2015
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DOI: 10.1038/ncomms7889

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