morphisms at the Microseminoprotein-β Locus ociatedwith Physiologic Variation in β-Microseminoprotein

ownloade kground: rs10993994, a single nucleotide polymorphism (SNP) at the genetic locus encoding βeminoprotein (β-MSP), is associated with both prostate cancer risk and levels of blood prostate-specific n (PSA), a biomarker used in prostate cancer screening. Therefore, we wished to determine the assobetween SNPs at MSMB, the gene encoding β-MSP, and the levels of prostate-produced biomarkers , PSA, and human kallikrein 2 (hK2) in blood and semen. thods: Blood and semen from 304 healthy young Swedish men (ages 18-21) were assayed for β-MSP, and hK2. SNPs around MSMB were genotyped from matched DNA and analyzed for quantitative ation with biomarker levels. Empirical P values were multiple test–corrected and the independence h SNP's effect was determined. ults: rs10993994 was significantly associated with the blood and semen levels of β-MSP (both P < 1.0 × 10) A (P = 0.00014 and P = 0.0019), and semen levels of hK2 (P = 0.00027). Additional copies of the prostate risk allele resulted in lower β-MSP but higher PSA levels, and singly explained 23% and 5% of the variation semen β-MSP and PSA, respectively. Additional SNPs at MSMB are associated with β-MSP and PSA ndently of rs10993994. clusions: SNPs at MSMB correlate with physiologic variation in β-MSP and PSA levels in the blood men of healthy young Swedish men. In particular, rs10993994 has a strong effect on β-MSP levels. act: Our results suggest a mechanism by which rs10993994 might predispose to prostate cancer and Imp raise the possibility that genetic variation might need to be considered in interpreting the levels of these biomarkers. Cancer Epidemiol Biomarkers Prev; 19(8); 2035–42. ©2010 AACR.