Lower prostate cancer risk in Swedish men with the androgen receptor E213 A-allele

Abstract

Background: In a previous population-based study on 3369 European men with self-reported prostate cancer (PCa), it was shown that androgen receptor (AR) haplotype designated H2 was associated with high levels of serum PSA (prostate-specific antigen) concentration, and, at the same time, with low risk for PCa. The aim of this study was to replicate this finding in other cohorts, with registry-based cancer diagnosis. Methods: Using data from two population-based cohorts; the Malmö Diet and Cancer Study (MDCS, n = 12,121) and the Swedish Osteoporotic fractures in men study (MrOS, n = 1,120), 628 men with PCa and 1,374 controls were identified and genotyped. PCa data were collected from the Swedish national cancer registry. PCa odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for carriers of the particular AR haplotype, tagged by the rs6624304 T-allele. Results: The 15% of men who were carriers of the AR haplotype H2 had approximately one-third lower risk for PCa diagnosis compared to those with the most common H1 variant (OR 0.65; 95% CI 0.45–0.94; p = 0.021). The same trend, although not statistically significant (OR 0.75; 95% CI 0.47–1.24; p = 0.275), was observed in MrOS Sweden. When both cohorts were merged, an even more significant result was observed (OR 0.68; 95% CI 0.51–0.90; p = 0.008). Conclusions: Swedish men with the variant AR haplotype H2, tagged by rs6624304, have significantly lower risk of PCa compared to those with the more common variant.