ASSOCIATION OF mtDNA COPY NUMBER, GLUCOCORTICOID RECEPTOR, AND INFLAMMATORY GENES POLYMORPHISMS WITH PROSTATE CANCER AMONG WEST AFRICAN MEN
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Prostate cancer (PCa) is the second most common malignancy diagnosed in men and the fifth leading cause of cancer death worldwide. It is characterized by considerable geo-ethnic disparity, with men of African descent showing an approximately 2.7-fold higher mortality rate than the global average. Altered levels of mitochondrial DNA copy number (mtDNA-CN) have been associated with a higher risk of PCa and changes in prostate glandular architecture, suggesting it is a potential cancer marker. Single nucleotide polymorphisms (SNPs) within the glucocorticoid receptor (GR) and inflammatory genes have been shown to induce modifications in signaling pathways and immunomodulatory responses. These genetic alterations have been implicated in amplifying the aggressiveness of PCa. This study aimed to determine the relationship between the mtDNA-CN, GR polymorphisms, and inflammatory genes polymorphisms among PCa patients recruited from Nigeria, Niger, and Benin Republic. The case-control study consisted of 166 PCa patients and 200 paired healthy controls. Multiplex qPCR was used to measure mtDNA-CN levels and TaqMan genotyping assay was used to determine the genotypes of GR - Tth111I (rs10052957), ER22 (rs6189), 23 EK (rs6190), NR3C1-1 (rs10482605), BclI (rs41423237), and 9β (rs6198) and inflammatory genes-IL-8(rs4073), IL-6(rs1800795), IFN-L4(rs-368234815) polymorphisms. The study found that PCa patients exhibited significantly elevated (p= 1.867e-06) mtDNA-CN compared to healthy controls. Pairwise comparisons between the GR SNPs showed a high linkage disequilibrium (LD) for 9β and Tth111I (D’ = 1, r2 = 0.083), BCL1 and Tth111I (D’= 0.782, r2 = 0.42) in controls. High LD was also observed for BCL1 and Tth111I (D’= 0.773, r2 = 0.511) and Intermediate LD for 9β and Tth111I (D’ = 1, r2 = 0.04) in cases. In conclusion, this study offers suggestive evidence regarding the impact of mtDNA-CN levels and SNPs on the susceptibility to PCa among West African men.
Keywords
QH Natural history, QH301 Biology