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Androgen receptor polymorphism dependent variation in prostate specific antigen concentrations of European men.

Bentmar Holgersson, Magdalena LU ; Giwercman, Aleksander LU ; Bjartell, Anders LU ; Wu, Frederick C W ; Huhtaniemi, Ilpo T ; O'Neill, Terence W ; Pendleton, Neil ; Vanderschueren, Dirk ; Lean, Michael E J and Han, Thang S , et al. (2014) In Cancer Epidemiology Biomarkers & Prevention 23(10). p.2048-2056
Abstract
Background Androgens acting via the androgen receptor (AR) stimulate production of prostate specific antigen (PSA), which is a clinical marker of prostate cancer (PCa). Since genetic variants in the AR may have a significant impact on the risk of being diagnosed with PCa, the aim was to investigate if AR-variants were associated with the risk of having PSA above clinically used cut-off thresholds of 3 or 4 ng/mL in men without PCa. Methods Men without PCa history (n=1744) were selected from the European Male Ageing Study (EMAS) cohort of 40-80 year old men from 8 different European centers. Using linear and logistic regression models, with age and center as covariates, we investigated whether AR-variants (CAG repeat-length and/or SNP... (More)
Background Androgens acting via the androgen receptor (AR) stimulate production of prostate specific antigen (PSA), which is a clinical marker of prostate cancer (PCa). Since genetic variants in the AR may have a significant impact on the risk of being diagnosed with PCa, the aim was to investigate if AR-variants were associated with the risk of having PSA above clinically used cut-off thresholds of 3 or 4 ng/mL in men without PCa. Methods Men without PCa history (n=1744) were selected from the European Male Ageing Study (EMAS) cohort of 40-80 year old men from 8 different European centers. Using linear and logistic regression models, with age and center as covariates, we investigated whether AR-variants (CAG repeat-length and/or SNP genotype) were associated with having serum PSA concentrations above 3 or 4 ng/mL, which often are set as cut-off concentrations for further investigation of PCa. Results Carriers of the SNP rs1204038 A-allele (16% of the men) were more likely to have PSA>3 and 4 ng/mL (OR; 95%CI 1.65; 1.13-2.40 and 1.87; 1.18-2.96, respectively) than G-allele carriers. They also had shorter CAG-repeats (median 20 vs. 23, p<0.0005), but CAG repeat length per se did not affect the PSA concentrations. Conclusion The A-allele of the SNP rs1204038 gives a 65% higher risk of having PSA above 3 ng/mL than the G-allele in men without PCa, and thereby an increased risk of being referred for further examination on suspicion of PCa. Impact Serum PSA as a clinical marker could be improved by adjustment for AR-genotype. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cancer Epidemiology Biomarkers & Prevention
volume
23
issue
10
pages
2048 - 2056
publisher
American Association for Cancer Research
external identifiers
  • pmid:25012998
  • wos:000345277400011
  • scopus:84907483721
  • pmid:25012998
ISSN
1538-7755
DOI
10.1158/1055-9965.EPI-14-0376
language
English
LU publication?
yes
id
a2da45a7-23fa-45a9-ac0c-a9db2564fa30 (old id 4583001)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25012998?dopt=Abstract
date added to LUP
2016-04-01 10:46:43
date last changed
2022-04-11 12:19:33
@article{a2da45a7-23fa-45a9-ac0c-a9db2564fa30,
  abstract     = {{Background Androgens acting via the androgen receptor (AR) stimulate production of prostate specific antigen (PSA), which is a clinical marker of prostate cancer (PCa). Since genetic variants in the AR may have a significant impact on the risk of being diagnosed with PCa, the aim was to investigate if AR-variants were associated with the risk of having PSA above clinically used cut-off thresholds of 3 or 4 ng/mL in men without PCa. Methods Men without PCa history (n=1744) were selected from the European Male Ageing Study (EMAS) cohort of 40-80 year old men from 8 different European centers. Using linear and logistic regression models, with age and center as covariates, we investigated whether AR-variants (CAG repeat-length and/or SNP genotype) were associated with having serum PSA concentrations above 3 or 4 ng/mL, which often are set as cut-off concentrations for further investigation of PCa. Results Carriers of the SNP rs1204038 A-allele (16% of the men) were more likely to have PSA&gt;3 and 4 ng/mL (OR; 95%CI 1.65; 1.13-2.40 and 1.87; 1.18-2.96, respectively) than G-allele carriers. They also had shorter CAG-repeats (median 20 vs. 23, p&lt;0.0005), but CAG repeat length per se did not affect the PSA concentrations. Conclusion The A-allele of the SNP rs1204038 gives a 65% higher risk of having PSA above 3 ng/mL than the G-allele in men without PCa, and thereby an increased risk of being referred for further examination on suspicion of PCa. Impact Serum PSA as a clinical marker could be improved by adjustment for AR-genotype.}},
  author       = {{Bentmar Holgersson, Magdalena and Giwercman, Aleksander and Bjartell, Anders and Wu, Frederick C W and Huhtaniemi, Ilpo T and O'Neill, Terence W and Pendleton, Neil and Vanderschueren, Dirk and Lean, Michael E J and Han, Thang S and Finn, Joseph D and Kula, Krzysztof and Forti, Gianni and Casanueva, Felipe F and Bartfai, György and Punab, Margus and Giwercman, Yvonne}},
  issn         = {{1538-7755}},
  language     = {{eng}},
  number       = {{10}},
  pages        = {{2048--2056}},
  publisher    = {{American Association for Cancer Research}},
  series       = {{Cancer Epidemiology Biomarkers & Prevention}},
  title        = {{Androgen receptor polymorphism dependent variation in prostate specific antigen concentrations of European men.}},
  url          = {{http://dx.doi.org/10.1158/1055-9965.EPI-14-0376}},
  doi          = {{10.1158/1055-9965.EPI-14-0376}},
  volume       = {{23}},
  year         = {{2014}},
}