AI Article Synopsis
- The study investigates the relationship between the KLK2 gene variants and prostate cancer risk, specifically analyzing five SNPs among 1,251 men with and without prostate cancer.
- Significant associations were found between specific KLK2 SNPs and increased likelihood of prostate cancer, with adjusted odds showing the A allele of KLK2-SNP1 and T allele of KLK2-SNP5 linked to higher risk.
- The research also indicates that certain KLK2 risk genotypes correlate with elevated hK2 serum levels, supporting the idea that KLK2 may contribute to prostate cancer susceptibility through increased hK2 production.
Article Abstract
Purpose: Increased levels of serum human kallikrein-2 (hK2) and an hK2 gene (KLK2) variant are positively associated for prostate cancer, but the relationships between them remain unclear. We examined five variants of the KLK2 gene to further define its relevance to prostate cancer susceptibility and hK2 levels.
Experimental Design: We genotyped 645 men with biopsy-proven prostate cancer (cases) and 606 males with biopsies negative for prostate cancer (controls) for five additional single nucleotide polymorphisms (SNP) across the KLK2 gene and also tested for serum hK2 levels. These SNPs were identified from sequencing the KLK2 gene among 20 patients with aggressive prostate cancer. Odds ratios (OR) for prostate cancer detection and haplotype analysis were done.
Results: Among the SNPs studied, the A allele of the KLK2-SNP1 (G>A, rs2664155) and the T allele of the KLK2-SNP5 (C>T, rs198977) polymorphisms showed positive associations with prostate cancer, adjusted ORs for KLK2-SNP1 AG and AA genotypes being 1.4 [95% confidence interval (95% CI), 1.2-1.8; P=0.002] and for KLK2-SNP5 TT or CT genotypes being 1.3 (95% CI, 1.1-1.6; P=0.05). Haplotype analyses also revealed a significant association between prostate cancer and the haplotype containing both risk alleles (ACCTT), OR being 5.1 (95% CI, 1.6-6.5; P=0.005). Analysis of serum hK2 revealed hK2 levels to be significantly increased in association with KLK2-SNP1 AA and AG risk genotypes compared with the GG genotype (P=0.001) and also in association with the ACCTT risk haplotype compared with the most common non-risk haplotype (P=0.05).
Conclusions: These findings suggest a role for the KLK2 gene in prostate cancer susceptibility and imply that this role may be realized at least in part by the induction of increases in hK2 production.
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| http://dx.doi.org/10.1158/1078-0432.CCR-06-1485 | DOI Listing |
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