Genetic association of the KLK4 locus with risk of prostate cancer

Lose, Felicity, Srinivasan, Srilakshmi, O'Mara, Tracy, Marquart, Louise, Chambers, Suzanne, Gardiner, Robert, Aitken, Joanne F., Spurdle, Amanda B., Batra, Jyotsna, & Clements, Judith (2012) Genetic association of the KLK4 locus with risk of prostate cancer. PLoS ONE, 7(9), e44520.

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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 (±10 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.

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ID Code: 57983
Item Type: Journal Article
Refereed: Yes
DOI: 10.1371/journal.pone.0044520
ISSN: 1553-7390
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200)
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > QUT Faculties and Divisions > Faculty of Law
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2012 The Authors
Deposited On: 11 Mar 2013 00:39
Last Modified: 22 Feb 2017 15:53

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