Polymorphisms at the Microseminoprotein-beta locus associated with physiologic variation in beta-microseminoprotein and prostate-specific antigen levels

Cancer Epidemiol Biomarkers Prev. 2010 Aug;19(8):2035-42. doi: 10.1158/1055-9965.EPI-10-0431.


Background: rs10993994, a single nucleotide polymorphism (SNP) at the genetic locus encoding beta-microseminoprotein (beta-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 beta-MSP, and the levels of prostate-produced biomarkers beta-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 beta-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 beta-MSP (both P < 1.0 x 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 beta-MSP but higher PSA levels, and singly explained 23% and 5% of the variation seen in semen beta-MSP and PSA, respectively. Additional SNPs at MSMB are associated with beta-MSP and PSA independently of rs10993994.

Conclusions: SNPs at MSMB correlate with physiologic variation in beta-MSP and PSA levels in the blood and semen of healthy young Swedish men. In particular, rs10993994 has a strong effect on beta-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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics*
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Polymorphism, Single Nucleotide*
  • Prostate-Specific Antigen / analysis*
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / genetics*
  • Prostatic Secretory Proteins / analysis
  • Prostatic Secretory Proteins / blood
  • Prostatic Secretory Proteins / genetics*
  • Semen / chemistry
  • Sweden
  • Tissue Kallikreins / analysis
  • Tissue Kallikreins / blood
  • Young Adult


  • Biomarkers, Tumor
  • Prostatic Secretory Proteins
  • beta-microseminoprotein
  • Tissue Kallikreins
  • Prostate-Specific Antigen