Polymorphisms at the microseminoprotein-β locus associated with physiologic variation in β-microseminoprotein and prostate-specific antigen levels Journal Article
| Authors: | Xu, X.; Valtonen-André, C.; Sävblom, C.; Halldén, C.; Lilja, H.; Klein, R. J. |
| Article Title: | Polymorphisms at the microseminoprotein-β locus associated with physiologic variation in β-microseminoprotein and prostate-specific antigen levels |
| Abstract: | Background: rs10993994, a single nucleotide polymorphism (SNP) at the genetic locus encoding β-microseminoprotein (β-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 β-MSP, and the levels of prostate-produced biomarkers β-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 β-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 β-MSP (both P < 1.0 × 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 β-MSP but higher PSA levels, and singly explained 23% and 5% of the variation seen in semen β-MSP and PSA, respectively. Additional SNPs at MSMB are associated with β-MSP and PSA independently of rs10993994. Conclusions: SNPs at MSMB correlate with physiologic variation in β-MSP and PSA levels in the blood and semen of healthy young Swedish men. In particular, rs10993994 has a strong effect on β-MSP levels. Impact: 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. ©2010 AACR. |
| Keywords: | adolescent; adult; controlled study; young adult; unclassified drug; polymorphism, single nucleotide; cancer risk; biological marker; prostate specific antigen; protein blood level; allele; genetic predisposition to disease; tumor markers, biological; gene locus; genotype; prostate cancer; sweden; prostate-specific antigen; prostatic neoplasms; correlation analysis; quantitative analysis; blood analysis; kallikrein; dna determination; normal human; semen analysis; dna polymorphism; human experiment; tissue kallikreins; beta microseminoprotein; prostatic secretory proteins; kallikrein 2; semen; microseminoprotein beta; prostate antigen |
| Journal Title: | Cancer Epidemiology Biomarkers and Prevention |
| Volume: | 19 |
| Issue: | 8 |
| ISSN: | 1055-9965 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2010-08-01 |
| Start Page: | 2035 |
| End Page: | 2042 |
| Language: | English |
| DOI: | 10.1158/1055-9965.epi-10-0431 |
| PUBMED: | 20696662 |
| PROVIDER: | scopus |
| PMCID: | PMC2946372 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 3" - "Export Date: 20 April 2011" - "CODEN: CEBPE" - "Source: Scopus" |
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