Polymorphism of the SRD5A2 gene and the risk of prostate cancer

Abstract

Abstract. Androgens are actively involved in the development of the prostate gland and appear to be essential for prostate carcinogenesis. The product of the SRD5A2 gene, membrane-bound steroid 5-α-reductase, type II enzyme, is key in testosterone metabolism. The present study explored the association between the SRD5A2 V89L gene polymorphism and the risk of developing prostate cancer. The study cohort consisted of 456 male Slovak patients, including 260 cases with histologically confirmed prostate cancer and 196 age-matched controls without any clinically suspected infections of the prostate. Polymerase chain reaction-restriction fragment length polymorphism analysis was used to detect the SRD5A2 polymorphism on codon 89. Odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs) for different allele variants were calculated in order to determine the association between the SRD5A2 V89L gene polymorphism and prostate cancer. The distribution of V89L variants in the control group was consistent with the Hardy-Weinberg equilibrium (χ 2 test, P=0.266) with a significant deviation in the case group (χ 2 test, P=0.04). However, no association between the SRD5A2 polymorphism and an increased risk of developing prostate cancer was identified. When the wild type VV variant was used as a reference, the ORs for different allele variants ranged from 1.11 (95% CI 0.66-1.87, P=0.70) for the LL genotype to 0.99 (95% CI 0.68-1.46, P=0.99) for the LL + VL genotypes. No particular allele variant was identified to exhibit an increased capacity to promote the development of highly aggressive prostate cancer (Gleason ≥7) or induce carcinogenesis at an earlier onset (<65 years of age). It was confirmed that in the population studied, the SRD5A2 V89L polymorphism was not associated with the risk of prostate cancer and SRD5A2 was not shown to be a key gene involved in prostate cancer development. Published data indicate that a combination of multiple genetic changes are required for prostate cancer development, rather than a single gene change. Therefore, it was hypothesized that high-throughput genotyping may be more effective than single nucleotide polymorphism detection.

Role of CD5L and SRD5A2 as Prognostic Biomarkers for Hepatocellular Carcinoma

“…Therefore, SRD5A2 V89L gene polymorphism has been associated with breast cancer and prostate cancer in previous studies. [26][27][28] In the present study, we found that SRD5A2 was an independent risk factor for RFS in HCC. Liver regulates the metabolism and activity of sex hormones.…”

The Molecular Basis of 5α-Reductase Type 2 Deficiency

“…The association of this polymorphism with androgenrelated cancer risk is even more controversial. No association between the p.Val89Leu polymorphism and an increased risk of developing prostate cancer was identified among 456 Slovak male patients [Dušenka et al, 2014]. On the contrary, the presence of p.Val89Leu polymorphism has been implicated as a risk for breast cancer development [Francis et al, 2014].…”