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 P(trend)<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 (r(2) ≥ 0.98). Our findings provide suggestive evidence of a role for genetic variation in the KLK4 locus in
prostate cancer predisposition.