MSMB gene variant alters the association between prostate cancer and number of sexual partners.

Recently, a genetic variant (rs10993994) in the MSMB gene associated with prostate cancer (PCa) risk was shown to correlate with reduced prostate secretory protein of 94 amino acids (PSP94) levels. Although the biological activity of PSP94 is unclear, one of its hypothesized functions is to protect prostatic cells from pathogens. Number of sexual partners and a history of sexually transmitted infections (STIs) have been positively associated with PCa risk, and these associations may be related to pathogen-induced chronic prostatic inflammation. Based on these observations, we investigated whether MSMB genotype modifies the PCa-sexual history association. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) for the association between number of sexual partners and PCa by fitting logistic regression models, stratified by MSMB genotype, and adjusted for age, family history of PCa, and PCa screening history among 1,239 incident cases and 1,232 controls. Compared with 1-4 female sexual partners, men with ≥ 15 such partners who carried the variant T allele of rs10993994 were at increased risk for PCa (OR = 1.32; 95% CI, 1.03-1.71); no association was observed in men with the CC genotype (OR = 1.03; 95% CI, 0.73-1.46; P = 0.05 for interaction). Similar estimates were observed for total sexual partners (any T allele OR = 1.37; 95% CI, 1.07-1.77; CC genotype OR = 1.11; 95% CI, 0.79-1.55; P = 0.06 for interaction). The rs10993994 genotype in the MSMB gene modifies the association between number of sexual partners and PCa risk. These findings support a hypothesized biological mechanism whereby prostatic infection/inflammation may enhance risk of PCa.