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Two susceptibility loci identified for prostate cancer aggressiveness

Author

Listed:
  • Sonja I. Berndt

    (National Cancer Institute)

  • Zhaoming Wang

    (National Cancer Institute
    Cancer Genomics Research Laboratory, National Cancer Institute, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research)

  • Meredith Yeager

    (National Cancer Institute
    Cancer Genomics Research Laboratory, National Cancer Institute, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research)

  • 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
    School of Public Health, University of Washington)

  • 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)

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.

Suggested Citation

  • Sonja I. Berndt & Zhaoming Wang & Meredith Yeager & Michael C. Alavanja & Demetrius Albanes & Laufey Amundadottir & Gerald Andriole & Laura Beane Freeman & Daniele Campa & Geraldine Cancel-Tassin & Fe, 2015. "Two susceptibility loci identified for prostate cancer aggressiveness," Nature Communications, Nature, vol. 6(1), pages 1-7, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7889
    DOI: 10.1038/ncomms7889
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