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Cancer Epidemiol Biomarkers Prev. 2014 Oct;23(10):2048-56. doi: 10.1158/1055-9965.EPI-14-0376. Epub 2014 Jul 10.

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

Author information

  • 1Department of Clinical Sciences, Molecular Genetic Reproduction Medicine, Lund University, Malmö, Sweden. magdalena.bentmar_holgersson@med.lu.se.
  • 2Department of Clinical Sciences, Molecular Reproduction Medicine, Skåne University Hospital, Lund University, Malmö, Sweden.
  • 3Department of Urology and Department of Clinical Sciences, Division of Urological Cancers Skåne University Hospital, Lund University, Malmö, Sweden.
  • 4Department of Medicine, Manchester Academic Health Science Centre, The University of Manchester, Manchester Royal Infirmary, Manchester, United Kingdom.
  • 5Department of Reproductive Biology, Imperial College London, London, United Kingdom.
  • 6Arthritis Research United Kingdom Epidemiology Unit, The University of Manchester, Manchester, United Kingdom.
  • 7School of Community Based Medicine, The University of Manchester, Salford Royal NHS Trust, Salford, United Kingdom.
  • 8Department of Andrology and Endocrinology, Katholieke Universiteit Leuven, Leuven, Belgium.
  • 9Division of Developmental Medicine, Human Nutrition Section, University of Glasgow, Glasgow, United Kingdom.
  • 10Department of Endocrinology, Royal Free and University College Hospital Medical School, Royal Free Hospital, London, United Kingdom.
  • 11Department of Andrology and Reproductive Endocrinology, Medical University of Łódź, Łódź, Poland.
  • 12Clinical Physiopathology, University of Florence, Florence, Italy.
  • 13Department of Medicine, Santiago de Compostela University, Complejo Hospitalario Universitario de Santiago, CIBER de Fisiopatología Obesidad y Nutricion, Instituto Salud Carlos III, Santiago de Compostela, Spain.
  • 14Department of Obstetrics, Gynecology and Andrology, University of Szeged, Szeged, Hungary.
  • 15Andrology Unit, United Laboratories of Tartu University Clinics, Tartu, Estonia.
  • 16Department of Clinical Sciences, Molecular Genetic Reproduction Medicine, Lund University, Malmö, Sweden.

Abstract

BACKGROUND:

Androgens acting via the androgen receptor (AR) stimulate production of PSA, which is a clinical marker of prostate cancer. Because genetic variants in the AR may have a significant impact on the risk of being diagnosed with prostate cancer, the aim was to investigate whether AR variants were associated with the risk of having PSA above clinically used cutoff thresholds of 3 or 4 ng/mL in men without prostate cancer.

METHODS:

Men without prostate cancer history (n = 1,744) were selected from the European Male Ageing Study cohort of 40 to 79-year-old men from eight 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 cutoff concentrations for further investigation of prostate cancer.

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% confidence intervals, 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 prostate cancer, and thereby an increased risk of being referred for further examination on suspicion of prostate cancer.

IMPACT:

Serum PSA as a clinical marker could be improved by adjustment for AR-genotype.

©2014 American Association for Cancer Research.

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PMID:
25012998
[PubMed - indexed for MEDLINE]
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