Association of Androgen Receptor (AR) CAG Repeats and Cytochrome P450 3A5*3 (CYP3A5*3) Gene Polymorphisms in South Indian Men with Prostate Cancer

Abstract

Introduction: Prostate Cancer (PCA) is the second most common cancer diagnosed in men worldwide. Prostate Specific Antigen (PSA) is the readily used biomarker for PCA screening, but lack of specificity limits its usefulness. Hence, role of Androgen receptor (AR) CAG repeat polymorphism and Cytochrome P450 3A5*3 gene polymorphism involved in the metabolism of testosterone, growth and differentiation of prostate gland were evaluated to assess their association with pathogenesis of prostate lesions. Aim: To determine CAG repeats in AR gene and CYP3A5*3 gene polymorphism in South Indian men with PCA and Benign Prostate Hyperplasia (BPH). Materials and Methods: Genomic DNA was isolated from 312 (100 men with PCA, 109 BPH patients and 103 controls). Formalin fixed paraffin embedded tissue/peripheral blood samples using salting out method were used. Polymerase Chain Reaction (PCR) procedure was carried out using specific primers for AR and CYP3A5*3 genes. Bands were visualised by electrophoresis on 2% ethidium bromide (EtBr) stained agarose gel. Odds ratios were calculated using MedCalcR version 18.2.1 and Chi-square analysis was carried out to determine the association among groups. Results: AR gene with <22 CAG repeats and ‘GG’ genotype of CYP3A5*3 gene polymorphism were identified in 61 (61%), PCA patients, 11 (10%) BPH and 13 (13%) control individuals. A statistically significant association was observed between AR short repeats and CYP3A5*3 ‘GG’ genotype with PCA (p-value <0.05). Conclusion: The results suggest that the best age for PCA screening is 48 years or above for early detection and prevention of this malignancy. A <22 CAG repeats in AR gene and ‘GG’ genotype of CYP3A5*3 (rs#776746) gene can be together considered as specific molecular marker for identifying men at a risk of developing PCA.

Keywords

• benign prostate hyperplasia
• genetic markers
• polymorphism
• prostate specific antigen