ASSOCIATION BETWEEN CYP17A1 AND HSD3B1 GENE POLYMORPHISMS AND TESTOSTERONE LEVELS IN NIGERIAN PROSTATE CANCER PATIENTS
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Prostate cancer (PCa) represents a significant worldwide health challenge, being the second most diagnosed cancer and a top cause of cancer-related deaths among men. African men exhibit high PCa incidence and mortality rates. Genetic variation in androgen pathways is essential in PCa development and progression. The Cytochrome P450 17A1 (CYP17A1) gene encodes a critical metabolic enzyme involved in testosterone (TT) synthesis, as it converts cholesterol into androstenedione. Similarly, the 3β-hydroxysteroid dehydrogenase type 1 (HSD3B1) gene encodes an enzyme that catalyses the conversion of dehydroepiandrosterone (DHEA) to androstenedione, a critical precursor for TT production. This study aimed to evaluate the frequency of polymorphisms in the CYP17A1 and HSD3B1 genes among PCa patients from Southwest Nigeria and to investigate their association with testosterone levels and androgen receptor (AR). The case-control study was conducted on 40 PCa patients and 40 control groups of healthy males with matching ages. Detection of CYP17A1 and HSD3B1 polymorphisms was done using TaqMan real-time polymerase chain reaction (RT-PCR), and estimation of TT and AR levels in serum was done using the enzyme-linked immune-sorbent assay (ELISA) technique for all groups. This study identified AA, AG, and GG genotypes of the CYP17A1 and AA and CA genotypes of HSD3B1, and there was no significant association between PCa and control groups of the genes. Testosterone levels were higher in the control group than in the PCa group (p=0.0015). There was no association was found between CYP17A1 gene polymorphisms and TT and AR levels, similar to the HSD3B1 gene and TT. Conversely, an association was found between the HSD3B1 heterozygous adrenal-restrictive (CA) and AR, and no HSD3B1 adrenal-permissive homozygous genotype (CC) was found. The result of this study suggests that the HSD3B1 gene could be a suggestive prognostic and predictive biomarker of PCa. This would pave the way for future investigations that could influence diagnosis and personalised treatment of PCa.
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QD Chemistry, QH Natural history, R Medicine (General), RA0421 Public health. Hygiene. Preventive Medicine