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Polymorphisms at the Microseminoprotein-beta Locus Associated with Physiologic Variation in beta-Microseminoprotein and Prostate-Specific Antigen Levels

Xu, Xing; Valtonen-André, Camilla LU ; Sävblom, Charlotta LU ; Halldén, Christer LU ; Lilja, Hans LU and Klein, Robert J. (2010) In Cancer Epidemiology Biomarkers & Prevention 19(8). p.2035-2042
Abstract
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... (More)
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. 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. Cancer Epidemiol Biomarkers Prev; 19(8); 2035-42. (C) 2010 AACR. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cancer Epidemiology Biomarkers & Prevention
volume
19
issue
8
pages
2035 - 2042
publisher
American Association for Cancer Research
external identifiers
  • wos:000280675000017
  • scopus:77955434607
ISSN
1538-7755
DOI
10.1158/1055-9965.EPI-10-0431
language
English
LU publication?
yes
id
4d87d575-afc7-4f88-b73c-f01754f38ecf (old id 1678482)
date added to LUP
2010-09-21 08:40:37
date last changed
2018-06-03 04:05:20
@article{4d87d575-afc7-4f88-b73c-f01754f38ecf,
  abstract     = {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 &lt; 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. 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. Cancer Epidemiol Biomarkers Prev; 19(8); 2035-42. (C) 2010 AACR.},
  author       = {Xu, Xing and Valtonen-André, Camilla and Sävblom, Charlotta and Halldén, Christer and Lilja, Hans and Klein, Robert J.},
  issn         = {1538-7755},
  language     = {eng},
  number       = {8},
  pages        = {2035--2042},
  publisher    = {American Association for Cancer Research},
  series       = {Cancer Epidemiology Biomarkers & Prevention},
  title        = {Polymorphisms at the Microseminoprotein-beta Locus Associated with Physiologic Variation in beta-Microseminoprotein and Prostate-Specific Antigen Levels},
  url          = {http://dx.doi.org/10.1158/1055-9965.EPI-10-0431},
  volume       = {19},
  year         = {2010},
}