Rs1691053

rs1691053 is located on chromosome 5p15.31 and is associated with SRD5A1, which encodes the 5α-reductase isoform 1. This SNP has shown to be associated with prostate cancer (PCA), which is affected by dihydrotestosterone (DHT), the most potent male hormone. DHT functions by directly activating the androgen receptor. SRD5A along with another steroid-5α-reductase gene, HSD3B1 located on chromosome 1p12, are involved with converting testosterone to the more potent androgen DHT.

In 2010, Setlur et al. investigated the associations between SNPs in genes, HSD3B1, SRD5A1/2, and AKR1C2, that are involved in converting testosterone to DHT and known to confer PCA risk. The cohort consisted of 426 men, 205 controls and 221 cases. They were selected based on a prostate-specific antigen screening test in Tyrol, Austria. The study found that individuals with AG or GG versus AA at rs1691053 associated with SRD5A1 have an odds ratio of 1.8 (95% CI, 1.04-3.13) with G being the risk allele. In addition, men carrying the AA genotype at rs6428830 associated with HSD3B1 have an odds ratio of 2.0 (95% CI: 1.1-4.1) compared to GG individuals. Overall, men carrying both risk alleles for SRD5A1 and HSD3B1 have an odds ratio of 3.1 (95% CI: 1.4-6.7) compared to men carrying neither with a p-value of 0.005.

rs1691053 is one of seven SNPs identified that is associated with SRD5A1 (the others are rs566202, rs4702379, rs248803, rs3797177, rs8192249, and rs30434). In addition, eight other SNPs were identified that are associated with HSD3B1 (rs6428830 and rs10754400), SRD5A2 (rs4952197, rs7594951, and rs806645), and AKR1C2 (rs11252866, rs11252867, and rs11816204). This study by Setlur et al. is the first to determine that 5α-reductase isoform 1 is related to PCA risk and the rs1691053 SNP might be used as a screening process in the future to decide whether to block the enzymatic activity of both isoforms of 5α-reductase for PCA chemoprevention.

More recently, a research group in Spain genotyped 494 consecutive Spanish patients diagnosed with nonmetastatic localized PCA for 32 SNPs in SRD5A1, SRD5A2, and CYP17A1. They were able to analyze genotypic and allelic frequencies and haplotypes. They found that there were two SNPs in SRD5A1, rs3822430 and rs1691053, that are associated with prostate-specific antigen levels.

Patients who are G carriers for both SNPs compared to AA-AA carriers are at a higher risk of having high prostate-specific antigen levels of greater than 20 ng/mL with an odds ratio of 2.812 (95% CI: 1.397-5.657) and a p-value of 0.004. Through a haplotype analysis, the researchers found that patients with PCA that is nonhomozygous for the haplotype GCTTGTAGTA are at a higher risk of having a larger clinical tumor size with an odds ratio of 3.823 (95% CI: 1.280-11.416) and a p-value of 0.016.