Two susceptibility loci identified for prostate cancer aggressiveness

African Ancestry Prostate Cancer GWAS Consortium

doi:10.1038/ncomms7889

Two susceptibility loci identified for prostate cancer aggressiveness

African Ancestry Prostate Cancer GWAS Consortium

Urology

Research output: Contribution to journal › Article › peer-review

84 Scopus citations

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.

Original language	English (US)
Article number	6889
Journal	Nature communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms7889
State	Published - May 5 2015

ASJC Scopus subject areas

General
Physics and Astronomy(all)
Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)

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10.1038/ncomms7889

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@article{b78a8839128e41afa9d8412f3970d604,

title = "Two susceptibility loci identified for prostate cancer aggressiveness",

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.",

author = "{African Ancestry Prostate Cancer GWAS Consortium} and Berndt, {Sonja I.} and Zhaoming Wang and Meredith Yeager and Alavanja, {Michael C.} and Demetrius Albanes and Laufey Amundadottir and Gerald Andriole and {Beane Freeman}, Laura and Daniele Campa and Geraldine Cancel-Tassin and Federico Canzian and Cornu, {Jean Nicolas} and Olivier Cussenot and Diver, {W. Ryan} and Gapstur, {Susan M.} and Henrik Gr{\"o}nberg and Haiman, {Christopher A.} and Brian Henderson and Amy Hutchinson and Hunter, {David J.} and Key, {Timothy J.} and Suzanne Kolb and Stella Koutros and Peter Kraft and {Le Marchand}, Loic and Sara Lindstr{\"o}m and Machiela, {Mitchell J.} and Ostrander, {Elaine A.} and Elio Riboli and Fred Schumacher and Afshan Siddiq and Stanford, {Janet L.} and Stevens, {Victoria L.} and Travis, {Ruth C.} and Tsilidis, {Konstantinos K.} and Jarmo Virtamo and Stephanie Weinstein and Fredrik Wilkund and Jianfeng Xu and {Lilly Zheng}, S. and Kai Yu and William Wheeler and Han Zhang and Joshua Sampson and Amanda Black and Kevin Jacobs and Hoover, {Robert N.} and Margaret Tucker and Chanock, {Stephen J.} and Murphy, {Adam B.}",

note = "Funding Information: This work was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH (Z01-CP010119, ZIA-CP010152-11) and in part by the National Institute of Environmental Health Sciences (Z01-ES049030). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services nor does mention of trade names, commercial products or organization indicate endorsement by the US Government. We thank Drs Christine Berg and Philip Prorok, Division of Cancer Prevention, NCI, the screening center investigators and staff of the PLCO Cancer Screening Trial, Mr Thomas Riley and staff at Information Management Services Inc. and Ms Barbara O{\textquoteright}Brien and staff at Westat Inc. for their contributions to the PLCO. Finally, we are grateful to the study participants for donating their time and making this study possible. Publisher Copyright: {\textcopyright} 2015 Macmillan Publishers Limited. All rights reserved.",

year = "2015",

month = may,

day = "5",

doi = "10.1038/ncomms7889",

language = "English (US)",

volume = "6",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Two susceptibility loci identified for prostate cancer aggressiveness

AU - African Ancestry Prostate Cancer GWAS Consortium

AU - Berndt, Sonja I.

AU - Wang, Zhaoming

AU - Yeager, Meredith

AU - Alavanja, Michael C.

AU - Albanes, Demetrius

AU - Amundadottir, Laufey

AU - Andriole, Gerald

AU - Beane Freeman, Laura

AU - Campa, Daniele

AU - Cancel-Tassin, Geraldine

AU - Canzian, Federico

AU - Cornu, Jean Nicolas

AU - Cussenot, Olivier

AU - Diver, W. Ryan

AU - Gapstur, Susan M.

AU - Grönberg, Henrik

AU - Haiman, Christopher A.

AU - Henderson, Brian

AU - Hutchinson, Amy

AU - Hunter, David J.

AU - Key, Timothy J.

AU - Kolb, Suzanne

AU - Koutros, Stella

AU - Kraft, Peter

AU - Le Marchand, Loic

AU - Lindström, Sara

AU - Machiela, Mitchell J.

AU - Ostrander, Elaine A.

AU - Riboli, Elio

AU - Schumacher, Fred

AU - Siddiq, Afshan

AU - Stanford, Janet L.

AU - Stevens, Victoria L.

AU - Travis, Ruth C.

AU - Tsilidis, Konstantinos K.

AU - Virtamo, Jarmo

AU - Weinstein, Stephanie

AU - Wilkund, Fredrik

AU - Xu, Jianfeng

AU - Lilly Zheng, S.

AU - Yu, Kai

AU - Wheeler, William

AU - Zhang, Han

AU - Sampson, Joshua

AU - Black, Amanda

AU - Jacobs, Kevin

AU - Hoover, Robert N.

AU - Tucker, Margaret

AU - Chanock, Stephen J.

AU - Murphy, Adam B.

N1 - Funding Information: This work was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH (Z01-CP010119, ZIA-CP010152-11) and in part by the National Institute of Environmental Health Sciences (Z01-ES049030). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services nor does mention of trade names, commercial products or organization indicate endorsement by the US Government. We thank Drs Christine Berg and Philip Prorok, Division of Cancer Prevention, NCI, the screening center investigators and staff of the PLCO Cancer Screening Trial, Mr Thomas Riley and staff at Information Management Services Inc. and Ms Barbara O’Brien and staff at Westat Inc. for their contributions to the PLCO. Finally, we are grateful to the study participants for donating their time and making this study possible. Publisher Copyright: © 2015 Macmillan Publishers Limited. All rights reserved.

PY - 2015/5/5

Y1 - 2015/5/5

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84929000290&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84929000290&partnerID=8YFLogxK

U2 - 10.1038/ncomms7889

DO - 10.1038/ncomms7889

M3 - Article

C2 - 25939597

AN - SCOPUS:84929000290

SN - 2041-1723

VL - 6

JO - Nature communications

JF - Nature communications

M1 - 6889

ER -

Two susceptibility loci identified for prostate cancer aggressiveness

Abstract

ASJC Scopus subject areas

UN SDGs

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