A common prostate cancer risk variant 5' of microseminoprotein-beta (MSMB) is a strong predictor of circulating beta-microseminoprotein (MSP) levels in multiple populations

Cancer Epidemiol Biomarkers Prev. 2010 Oct;19(10):2639-46. doi: 10.1158/1055-9965.EPI-10-0427. Epub 2010 Aug 24.

Abstract

Background: β-Microseminoprotein (MSP) is one of the three most abundantly secreted proteins of the prostate and has been suggested as a biomarker for prostate cancer risk. A common variant, rs10993994, in the 5' region of the gene that encodes MSP (MSMB) has recently been identified as a risk factor for prostate cancer.

Methods: We examined the association between rs10993994 genotype and MSP levels in a sample of 500 prostate cancer-free men from four racial/ethnic populations in the Multiethnic Cohort (European Americans, African Americans, Latinos, and Japanese Americans). Generalized linear models were used to estimate the association between rs10993994 genotype and MSP levels.

Results: We observed robust associations between rs10994994 genotype and MSP levels in each racial/ethnic population (all P < 10(-8)), with carriers of the C allele having lower geometric mean MSP levels (ng/mL; CC/CT/TT genotypes: European Americans, 28.8/20.9/10.0; African Americans, 29.0/21.9/10.9; Latinos, 29.2/17.1/8.3; and Japanese Americans, 25.8/16.4/6.7). We estimated the variant accounts for 30% to 50% of the variation in MSP levels in each population. We also observed significant differences in MSP levels between populations (P = 3.5 × 10(-6)), with MSP levels observed to be highest in African Americans and lowest in Japanese Americans.

Conclusions: Rs10993994 genotype is strongly associated with plasma MSP levels in multiple racial/ethnic populations.

Impact: This supports the hypothesis that rs10993994 may be the biologically functional allele.

Publication types

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

MeSH terms

  • Aged
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics*
  • Cohort Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / ethnology
  • Prostatic Neoplasms / genetics*
  • Prostatic Secretory Proteins / blood
  • Prostatic Secretory Proteins / genetics*
  • Racial Groups

Substances

  • Biomarkers, Tumor
  • Prostatic Secretory Proteins
  • beta-microseminoprotein