Genetic Association of the KLK4 Locus with Risk of Prostate Cancer

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Title Genetic Association of the KLK4 Locus with Risk of Prostate Cancer
Author Lose, Felicity; Srinivasan, Srilakshmi; O'Mara, Tracy; Marquart, Louise; Chambers, Suzanne Kathleen; Gardiner, Robert A.; Aitken, Joanne; BioResource, The Australian Prostate Cancer; Spurdle, Amanda B.; Batra, Jyotsna; Clements, Judith A.
Journal Name PLoS One
Year Published 2012
Place of publication United States
Publisher Public Library of Science
Abstract The Kallikrein-related peptidase, KLK4, has been shown to be significantly overexpressed in prostate tumours in numerous studies and is suggested to be a potential biomarker for prostate cancer. KLK4 may also play a role in prostate cancer progression through its involvement in epithelial-mesenchymal transition, a more aggressive phenotype, and metastases to bone. It is well known that genetic variation has the potential to affect gene expression and/or various protein characteristics and hence we sought to investigate the possible role of single nucleotide polymorphisms (SNPs) in the KLK4 gene in prostate cancer. Assessment of 61 SNPs in the KLK4 locus (610 kb) in approximately 1300 prostate cancer cases and 1300 male controls for associations with prostate cancer risk and/or prostate tumour aggressiveness (Gleason score ,7 versus $7) revealed 7 SNPs to be associated with a decreased risk of prostate cancer at the Ptrend,0.05 significance level. Three of these SNPs, rs268923, rs56112930 and the HapMap tagSNP rs7248321, are located several kb upstream of KLK4; rs1654551 encodes a non-synonymous serine to alanine substitution at position 22 of the long isoform of the KLK4 protein, and the remaining 3 risk-associated SNPs, rs1701927, rs1090649 and rs806019, are located downstream of KLK4 and are in high linkage disequilibrium with each other (r2$0.98). Our findings provide suggestive evidence of a role for genetic variation in the KLK4 locus in prostate cancer predisposition.
Peer Reviewed Yes
Published Yes
Alternative URI http://dx.doi.org/10.1371/journal.pone.0044520
Copyright Statement Copyright 2012 Lose et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License CCAL. (http://www.plos.org/journals/license.html)
Volume 7
Issue Number 9
Page from e44520-1
Page to e44520-14
ISSN 1932-6203
Date Accessioned 2012-09-14
Date Available 2013-06-14T05:17:41Z
Language en_US
Research Centre Behavioural Basis of Health; Centre for Health Practice Innovation
Faculty Griffith Health Faculty
Subject Cancer Genetics
URI http://hdl.handle.net/10072/47773
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

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