Journal article
Genetic Association of the KLK4 Locus with Risk of Prostate Cancer
PLoS One, Vol.7(9)
2012
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. © 2012 Lose et al.
Details
- Title
- Genetic Association of the KLK4 Locus with Risk of Prostate Cancer
- Authors
- Felicity Lose (Author) - Queensland Institute of Medical ResearchS Srinivasan (Author) - Queensland University of TechnologyT O'Mara (Author) - Queensland Institute of Medical ResearchL Marquart (Author) - Queensland Institute of Medical ResearchS Chambers (Author) - Griffith UniversityR A Gardiner (Author) - University of QueenslandJ F Aitken (Author) - Griffith UniversityT Yeadon (Author)P Saunders (Author)A Eckert (Author)Judith A Clements (Author) - Queensland University of TechnologyP Heathcote (Author)G Wood (Author)G Malone (Author)H Samaratunga (Author)A Collins (Author)Megan Turner (Author)K Kerr (Author)A B Spurdle (Author) - Queensland Institute of Medical ResearchJ Batra (Author) - Queensland Institute of Medical Research
- Publication details
- PLoS One, Vol.7(9); 14
- Publisher
- Public Library of Science
- Date published
- 2012
- DOI
- 10.1371/journal.pone.0044520
- ISSN
- 1932-6203
- Copyright note
- Copyright © 2012 Lose et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
- Organisation Unit
- University of the Sunshine Coast, Queensland; Office of Research
- Language
- English
- Record Identifier
- 99450425602621
- Output Type
- Journal article
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- Oncology
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