Genetic association in CYP3A4 and CYP3A5 genes elevate the risk of prostate cancer

Abstract

Background CYP3A4 and CYP3A5 are biologically potential genes responsible for prostate cancer. Aim We aimed to analyse the expression and association of CYP3A4 and CYP3A5 genes in prostate cancer. Subjects and methods Web-based bioinformatics tools were used to assess the association of CYP3A4 and CYP3A5 genes with prostate cancer risks. A case-control study of 210 prostate cancer cases and 207 controls was also approved to determine the allelic variants of the CYP3A4 gene- rs2740574 (CYP3A4*1B) and the variant of CYP3A5 gene-rs776746 (CYP3A5*3) using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). The risk of prostate cancer was estimated as odds ratio (OR) and 95% confidence interval (CI) using unrestricted logistic regression models. Results Our in silico data confirmed that both CYP3A4 and CYP3A5 genes are significantly associated with higher prostate cancer risks. In the case of CYP3A4*1B polymorphism, the heterozygote (*1 A/*1B), mutant (*1B/*1B), and combined heterozygote plus mutant (*1A/*1B+*1B/*1B) genotypes showed 3.52-fold, 3.90-fold, and 3.67-fold increased risk of prostate cancer, respectively. In the case of CYP3A5*3 polymorphism, the heterozygote (*1/*3), mutant (*3/*3), and combined (*1/*3+*3/*3) genotypes were found to be significantly associated with 5.11-, 5.49-, and 5.28-fold greater risk of prostate cancer, respectively. Conclusion Our results indicate that CYP3A4*1B and CYP3A5*3 are significantly associated with increased prostate cancer risk.