Polymorphisms at the Microseminoprotein-beta Locus Associated with Physiologic Variation in beta-Microseminoprotein and Prostate-Specific Antigen Levels

Background: rs10993994, a single nucleotide polymorphism (SNP) at the genetic locus encoding β-microseminoprotein (β-MSP), is associated with both prostate cancer risk and levels of blood prostate-specific antigen (PSA), a biomarker used in prostate cancer screening. Therefore, we wished to determine the association between SNPs at MSMB , the gene encoding β-MSP, and the levels of prostate-produced biomarkers β-MSP, PSA, and human kallikrein 2 (hK2) in blood and semen. Methods: Blood and semen from 304 healthy young Swedish men (ages 18-21) were assayed for β-MSP, PSA, and hK2. SNPs around MSMB were genotyped from matched DNA and analyzed for quantitative association with biomarker levels. Empirical P values were multiple test–corrected and the independence of each SNP's effect was determined. Results: rs10993994 was significantly associated with the blood and semen levels of β-MSP (both P < 1.0 × 10−7) and PSA ( P = 0.00014 and P = 0.0019), and semen levels of hK2 ( P = 0.00027). Additional copies of the prostate cancer risk allele resulted in lower β-MSP but higher PSA levels, and singly explained 23% and 5% of the variation seen in semen β-MSP and PSA, respectively. Additional SNPs at MSMB are associated with β-MSP and PSA independently of rs10993994. Conclusions: SNPs at MSMB correlate with physiologic variation in β-MSP and PSA levels in the blood and semen of healthy young Swedish men. In particular, rs10993994 has a strong effect on β-MSP levels. Impact: Our results suggest a mechanism by which rs10993994 might predispose to prostate cancer and raise the possibility that genetic variation might need to be considered in interpreting the levels of these biomarkers. Cancer Epidemiol Biomarkers Prev; 19(8); 2035–42. ©2010 AACR. This article is featured in Highlights of This Issue, [p. 1887][1] [1]: /lookup/volpage/19/1887