POTENTIAL FOR THE PREDICTION OF PROSTATE CANCER RISK USING HAPLOTYPES IN EXON 5 OF KLK2 GENE

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POTENTIAL FOR THE PREDICTION OF PROSTATE CANCER RISK USING HAPLOTYPES IN EXON 5 OF KLK2 GENE

ABSTRACT

BACKGROUND:

Prostate cancer is the most common neoplasia of middle aged men .Early detection is problematic due to the lack of marker that has high sensitivity and specificity. Our aim was to genetically predict the possibility of developing prostate cancer using haplotypes in exon 5 of kLk2 gene. We evaluated polymorphisms in human glandular kallikreins 2 (KLK2) genes because a protein product of this gene is known to be increased in prostate cancer. SUBJECTS AND METHODS: Blood samples were collected from one hundred participants who had given their informed consent. Total, free and percentage PSA was measured using enzyme linked immunosorbent assays. Genomic DNA was extracted from whole blood using Spin column method. Exon 5 of KLK2 gene was amplified with specific primers. The PCR products were sequenced on ABI 3130 genetic analyzer. Sequence data were aligned and SNPs picked using the SeqMan alignment program of DNA Star software. RESULTS: Of the 100 subjects studied, 28% had elevated PSA above 4.0 ng/ml, which is a strong indicator of prostate cancer.Their total PSA, free PSA and percentage PSA mean value were 4.37, 0.49 and 15.16 respectively. Following the alignment, 12 SNPs of which 11 are curated in NCBI SNP database and one uncurated SNP were identified. Analysis of variance test on the various SNPs according to their PSA levelsshowed a statistically significant difference (p value: 0.0001). Two SNPs were significantly associated with elevated PSA levels and presence of prostate cancer in four subjects: rs370841038 and rs1064703. The identified SNPs constitute a genetic risk for prostate cancer development. The presence of both SNPs may be used as a genetic tool for stratifying patients into genetically high risk, medium and low risks subjects. This will influence the frequency and suitability of both mass screening and individual prostate cancer screening programmes.

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