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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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published
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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
ISSN
1538-7755
DOI
10.1158/1055-9965.EPI-14-0376
language
English
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yes
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a2da45a7-23fa-45a9-ac0c-a9db2564fa30 (old id 4583001)
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http://www.ncbi.nlm.nih.gov/pubmed/25012998?dopt=Abstract
date added to LUP
2014-08-07 20:13:59
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2017-09-10 03:20:30
@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},
  volume       = {23},
  year         = {2014},
}