Genome-Wide Association Study of CYP3A4 and CYP3A5 genes in relation to the risk of Prostate Cancer among Bangladeshi population

Abstract

Abstract ObjectivesCYP3A4 and CYP3A5 are biologically potential genes responsible for prostate cancer, but very few studies have reported on Bangladeshi population. Materials and methodsWeb-based bioinformatics tools were used to assessed the association of CYP3A4 and CYP3A5 genes with prostate cancer risks. A case-control study was also approved on 210 prostate cancer cases and 207 controls 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.ResultIn case of CYP3A4*1B polymorphism, the heterozygote (*1A/*1B), mutant (*1B/*1B), and combined heterozygote plus mutant (*1A/*1B+*1B/*1B) genotypes showed 3.52-fold (OR= 3.52, 95% CI= 1.38 to 9.02, p= 0.0086), 3.90-fold (OR= 3.90, 95%CI= 1.26 to 12.05, p= 0.0183) and 3.67-fold (OR= 3.67, 95%CI= 1.76 to 7.67, p= 0.0005) increased risk of prostate cancer, respectively. The variant CYP3A4*1B allele was significantly associated with an increased risk of prostate cancer (OR= 3.60, 95%CI= 1.95 to 6.65, p=0.0001). In 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 (OR= 5.11, 95%CI= 2.54 to 10.31, p= 0.0001; OR= 5.49, 95%CI= 2.45 to 12.28, p= 0.0001; OR= 5.28, 95% CI= 2.65 to 10.50, p= 0.0001, respectively). The variant CYP3A5*3 allele revealed significant association with increased susceptibility to prostate cancer (OR= 4.78, 95%CI= 3.05 to 7.48, p= 0.0001).ConclusionOur results indicate that CYP3A4*1B and CYP3A5*3 are significantly associated with increased prostate cancer risk.