2p23.1

Prostate cancer

Various genetic studies from multiple ethnic populations have shown genetic variations in the SRD5A2 gene are associated with prostate cancer. Polymorphisms V89L, A29T, and the (TA)n repeat are some of well-known SRD5A2 variation that have been liked to prostate cancer risk. However, these associations are not always consistent. For example, the V89L (rs523349) variant is a missense single nucleotide polymorphism resulting in a valine to leucine substitution at condon 89 that reduced SRD5A2 enzyme activity. More than couple dozen of studies performed genetic association studies between V89L polymorphism and prostate cancer risk since 1997. Although the association has been found significant repeatedly, the results were inconsistent and conflicting (Nam et al., 2001; Salam et al., 2005, Hsing et al., 2001). Recently, a meta-analysis review (Wang et al., 2010) was conducted on 25 genetic studies of SRD5A2 V89L polymorphism and prostate cancer, which included additional subgroup analysis in Asian, African, European and age ≤ 65 group. In overall analysis, no significant association was found between V89L and prostate cancer risk. Subgroup analysis revealed a slight but significant increased risk in European men with at least one L-allele (LL+LV vs VV, OR=1.11; 95%CI=1.03-1.19; P

Androgen levels have been suggested to play an important role in the etiology of prostate cancer. The same SRD5A2 genetic variations linked to prostate cancer has also been repeatedly shown to be associated with various circulating androgen level in the blood, including testosterone, dihydrotestosterone and various forms of their metabolites (Makridakis et al., 2000; Allen et al., 2001; Hsing et al., 2001). Therefore, it is possible that these risk-predisposing polymorphisms may cause changes in the SRD5A2 enzyme functional activity that results in the variation of circulating androgens, and ultimately leads to the development of prostate cancer.