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 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.


CONCLUSIONS
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.
Xu
Xing
X
Program in Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.
Valtonen-André
Camilla
C
Sävblom
Charlotta
C
Halldén
Christer
C
Lilja
Hans
H
Klein
Robert J
RJ
D000293:Adolescent; D014408:Biomarkers, Tumor / Q000032:analysis / Q000097:blood / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D017430:Prostate-Specific Antigen / Q000032:analysis* / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000235:genetics*; D029584:Prostatic Secretory Proteins / Q000032:analysis / Q000097:blood / Q000235:genetics*; D012661:Semen / Q000737:chemistry; D013548:Sweden; D020840:Tissue Kallikreins / Q000032:analysis / Q000097:blood; D055815:Young Adult
D014408:Biomarkers, Tumor; D029584:Prostatic Secretory Proteins; C043076:beta-microseminoprotein; D020840:Tissue Kallikreins; D017430:Prostate-Specific Antigen