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


CONCLUSIONS
This supports the hypothesis that rs10993994 may be the biologically functional allele.
Waters
Kevin M
KM
Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California, USA.
Stram
Daniel O
DO
Le Marchand
Loic
L
Klein
Robert J
RJ
Valtonen-André
Camilla
C
Peltola
Mari T
MT
Kolonel
Laurence N
LN
Henderson
Brian E
BE
Lilja
Hans
H
Haiman
Christopher A
CA
D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D015331:Cohort Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000097:blood / Q000208:ethnology / Q000235:genetics*; D029584:Prostatic Secretory Proteins / Q000097:blood / Q000235:genetics*; D044469:Racial Groups
D014408:Biomarkers, Tumor; D029584:Prostatic Secretory Proteins; C043076:beta-microseminoprotein