GENETIC POLYMORPHISMS IN ERCC6 AND CYP17A1 AND THEIR ASSOCIATION WITH VITAMIN-D LEVELS IN NIGERIAN PROSTATE CANCER PATIENTS

Abstract

Prostate cancer (PCa) constitutes the principal cause of cancer-related deaths among males over 40 in Africa, especially in Nigeria. By 2030, 10.8% of males may develop PCa before 75. The aggressiveness of PCa in Blacks versus Caucasians is not well understood. Mutations in tumour-specific genes like Excision Repair Cross-Complementation Group 6 (ERCC6) and Cytochrome P450 Family 17 Subfamily A Member 1 (CYP17A1) may serve as diagnostic biomarkers. ERCC6, involved in DNA repair, and CYP17A1, key in androgen production, are linked to PCa progression. This study assessed ERCC6 rs2228528 and CYP17A1 rs4919686 polymorphisms and their relation to vitamin D (VD) and androgen receptor (AR) levels in Nigerian PCa patients. Vitamin D (VD) insufficiency is linked with increased prostate cancer (PCa) mortality and influences energy metabolism in normal prostate cells. The Androgen Receptor (AR) regulates vital genes in prostate cancer development and is more common in Black populations. Exploring ERCC6 and CYP17A1 in relation to VD and AR could improve PCa diagnosis. This study evaluated the association between ERCC6 rs2228528 (C > T) and CYP17A1 rs4919686 (A > C) polymorphisms, located in ERCC6 exon 11 and the CYP17A1 promoter, respectively, vis-à-vis VD and AR levels in Nigerian PCa patients. Genotyping employed real-time PCR with TaqMan assays, while enzyme-linked immunosorbent assay (ELISA) was used to measure VD and AR levels. The data was then analysed using Excel, SPSS, and R. Results revealed a higher presence of ERCC6 rs2228528 wildtype genotypes in cases (37%) compared to controls (30%) and a lower presence of CYP17A1 rs4919686 wildtype genotypes in cases (46%) versus controls (48%). No significant associations (p > 0.05) were found between these polymorphisms. Nevertheless, rs2228528 shows promise as a PCa biomarker. VD levels were higher in cases (52.49 ng/mL) than in control (47.93 ng/mL), while difference in androgen levels were not significant (p > 0.05). Lastly, ERCC6 polymorphism, but not CYP17A1, shows potential as a possible biomarker for PCa. Larger studies are needed for definitive conclusions.