Potential for the Prediction of Prostate Cancer Risk Using Haplotypes of Exon1 Of Klk2 Gene

ABSTRACT Prostate cancer is the third most common cancer in Nigeria and the most underscreened cancer in Nigeria. It is the commonest type of cancer in men of African origin. Most prostate cancer cases in Nigeria are detected at the metastatic stage. The daily pick up of new cases is on the increase especially in tertiary hospitals with most men having advanced and high grade disease high who never gone for medical treatment. PSA testing lacks the ability to characterize prostate disease molecularly. Due to the above reason, many biomarkers for its diagnosis are now in existence. The human glandular kallikreins is one of such biomarkers. A member of this kallikrein gene family called “human glandular kallikrein 2(hk2) has a strong association with prostate cancer and it has been used as both prognostic and diagnostic marker. Single nucleotide polymorphisms (SNPs) in KLK2 and other biomarkers have been noticed to replace the diagnostic value of PSA testing in men who have high total PSA value. There is no documented data on molecular stratification of those at risk of developing prostate cancer. This study examined the clusters of SNPs (haplotypes) in exon 1 of KLK2 in men who have high and low PSA values. Subject and Method: 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 1 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: The total PSA values range from 4.11 – 50.63ng/ml, free PSA values range from 0.20 - 4.73ng/ml and calculated percentage free PSA values range from 1.9% -25.80%. After the alignment, nine SNPs were identified namely; rs187716365, rs367898018, rs112295394, rs62113073, rs2664156, rs369907394, rs2070854, rs201923328. Eight of these identified SNPs are curated (stored) in NCBI database, while one was uncurated. Three SNPs (rs112295394, rs2664156 and rs201923328) were significantly linked to elevated serum PSA levels (p