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

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.

• Authors: Kevin M Waters, Daniel O Stram, Loic Le Marchand, Robert J Klein, Camilla Valtonen-André, Mari T Peltola, Laurence N Kolonel, Brian E Henderson, Hans Lilja, Christopher A Haiman
• Journal: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology (Cancer Epidemiol Biomarkers Prev) Vol. 19 Issue 10 Pg. 2639-46 (Oct 2010) ISSN: 1538-7755 [Electronic] United States
• PMID: 20736317 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: ©2010 AACR.

Chemical References

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

Topics

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