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

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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
Article number	6889
Journal	Nature communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms7889
State	Published - May 5 2015

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@article{0ae97c0d1d804393a9cc4f5be1ab755b,

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 Ingles, {Sue A.}",

year = "2015",

month = may,

day = "5",

doi = "10.1038/ncomms7889",

language = "English",

volume = "6",

journal = "Nature communications",

issn = "2041-1723",

}

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 - Ingles, Sue A.

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

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

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