Two susceptibility loci identified for prostate cancer aggressiveness

被引：0

作者：

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

Stephen J. Chanock

机构：

[1] National Cancer Institute,Division of Cancer Epidemiology and Genetics

[2] Cancer Genomics Research Laboratory,Division of Cancer Epidemiology and Genetics

[3] National Cancer Institute,Division of Urologic Surgery

[4] Leidos Biomedical Research Inc.,Division of Cancer Epidemiology

[5] Frederick National Laboratory for Cancer Research,Department of Medical Epidemiology and Biostatistics

[6] Washington University School of Medicine,Department of Preventative Medicine

[7] German Cancer Research Center (DKFZ),Department of Epidemiology

[8] CeRePP,Nuffield Department of Clinical Medicine

[9] Assistance Publique-Hôpitaux de Paris,Division of Public Health Sciences

[10] UPMC University Paris 6,Department of Epidemiology and Biostatistics

[11] Genomic Epidemiology Group,Department of Genomics of Common Disease

[12] German Cancer Research Center (DKFZ),Department of Epidemiology

[13] Epidemiology Research Program,Department of Hygiene and Epidemiology

[14] American Cancer Society,Department of Chronic Disease Prevention

[15] Karolinska Institute,Department of Epidemiology

[16] Keck School of Medicine,Department of Public Health Sciences

[17] University of Southern California/Norris Comprehensive Cancer Center,Department of Preventive Medicine

[18] Harvard School of Public Health,Division of Epidemiology, Department of Medicine

[19] Cancer Epidemiology Unit,Department of Urology

[20] University of Oxford,Department of Urology

[21] Fred Hutchinson Cancer Research Center,Department of Epidemiology and Biostatistics

[22] Epidemiology Program,Department of Surgery

[23] University of Hawaii Cancer Center,undefined

[24] National Human Genome Research Institute,undefined

[25] National Institutes of Health,undefined

[26] School of Public Health,undefined

[27] Imperial College,undefined

[28] School of Public Health,undefined

[29] Imperial College London,undefined

[30] School of Public Health,undefined

[31] University of Washington,undefined

[32] University of Ioannina School of Medicine,undefined

[33] National Institute for Health and Welfare,undefined

[34] Center for Cancer Genomics,undefined

[35] Wake Forest University School of Medicine,undefined

[36] Information Management Services Inc.,undefined

[37] University of Arizona College of Medicine and University of Arizona Cancer Center,undefined

[38] University of Texas M.D. Anderson Cancer Center,undefined

[39] Henry Ford Hospital,undefined

[40] Stony Brook University,undefined

[41] James Buchanan Brady Urological Institute,undefined

[42] Johns Hopkins Hospital and Medical Institution,undefined

[43] Vanderbilt Epidemiology Center,undefined

[44] Vanderbilt University School of Medicine,undefined

[45] University of Texas M.D. Anderson Cancer Center,undefined

[46] Korle Bu Teaching Hospital,undefined

[47] University of Ghana Medical School,undefined

[48] Westat,undefined

[49] Rockville,undefined

[50] School of Public Health,undefined

来源：

Nature Communications | / 6卷

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摘要：

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.

引用

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