Two susceptibility loci identified for prostate cancer aggressiveness.
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.
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA.
Sonja I
SI
Berndt
1] Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA [2] Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland 21701, USA.
Zhaoming
Z
Wang
1] Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA [2] Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland 21701, USA.
Meredith
M
Yeager
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA.
Michael C
MC
Alavanja
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA.
Demetrius
D
Albanes
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA.
Laufey
L
Amundadottir
Division of Urologic Surgery, Washington University School of Medicine, St Louis, Missouri 63110, USA.
Gerald
G
Andriole
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA.
Laura
L
Beane Freeman
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
Daniele
D
Campa
CeRePP, Assistance Publique-Hôpitaux de Paris, UPMC University Paris 6, Paris, France.
Geraldine
G
Cancel-Tassin
Genomic Epidemiology Group, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
Federico
F
Canzian
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA.
Jean-Nicolas
JN
Cornu
CeRePP, Assistance Publique-Hôpitaux de Paris, UPMC University Paris 6, Paris, France.
Olivier
O
Cussenot
Epidemiology Research Program, American Cancer Society, Atlanta, Georgia 30303, USA.
W Ryan
WR
Diver
Epidemiology Research Program, American Cancer Society, Atlanta, Georgia 30303, USA.
Susan M
SM
Gapstur
Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm 17177, Sweden.
Henrik
H
Grönberg
Department of Preventative Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California 90033, USA.
Christopher A
CA
Haiman
Department of Preventative Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California 90033, USA.
Brian
B
Henderson
Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland 21701, USA.
Amy
A
Hutchinson
Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
David J
DJ
Hunter
Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7BN, UK.
Timothy J
TJ
Key
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
Suzanne
S
Kolb
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA.
Stella
S
Koutros
Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Peter
P
Kraft
Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii 96813, USA.
Loic
L
Le Marchand
Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Sara
S
Lindström
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA.
Mitchell J
MJ
Machiela
National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Elaine A
EA
Ostrander
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London SW7 2AZ, UK.
Elio
E
Riboli
Department of Preventative Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California 90033, USA.
Fred
F
Schumacher
Department of Genomics of Common Disease, School of Public Health, Imperial College London, London SW7 2AZ, UK.
Afshan
A
Siddiq
1] Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA [2] Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington 98195, USA.
Janet L
JL
Stanford
Epidemiology Research Program, American Cancer Society, Atlanta, Georgia 30303, USA.
Victoria L
VL
Stevens
Cancer Epidemiology Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7BN, UK.
Ruth C
RC
Travis
Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina 45110, Greece.
Konstantinos K
KK
Tsilidis
Department of Chronic Disease Prevention, National Institute for Health and Welfare, FI-00271 Helsinki, Finland.
Jarmo
J
Virtamo
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA.
Stephanie
S
Weinstein
Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm 17177, Sweden.
Fredrik
F
Wilkund
Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
Jianfeng
J
Xu
Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
S
S
Lilly Zheng
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA.
Kai
K
Yu
Information Management Services Inc., Rockville, Maryland 20852, USA.
William
W
Wheeler
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA.
Han
H
Zhang
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA.
Joshua
J
Sampson
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA.
Amanda
A
Black
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA.
Kevin
K
Jacobs
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA.
Robert N
RN
Hoover
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA.
Margaret
M
Tucker
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA.
Stephen J
SJ
Chanock
D016022:Case-Control Studies; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*