title: Androgen receptor polymorphism-dependent variation in prostate-specific antigen concentrations of European men.
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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  Serum PSA as a clinical marker could be improved by adjustment for AR-genotype.
authors.affiliation: Department of Clinical Sciences, Molecular Genetic Reproduction Medicine, Lund University, Malmö, Sweden. magdalena.bentmar_holgersson@med.lu.se.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Bentmar Holgersson
authors.affiliation: Department of Clinical Sciences, Molecular Reproduction Medicine, Skåne University Hospital, Lund University, Malmö, Sweden.
authors.forename: Aleksander
authors.initials: A
authors.lastname: Giwercman
authors.affiliation: Department of Urology and Department of Clinical Sciences, Division of Urological Cancers Skåne University Hospital, Lund University, Malmö, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Bjartell
authors.affiliation: Department of Medicine, Manchester Academic Health Science Centre, The University of Manchester, Manchester Royal Infirmary, Manchester, United Kingdom.
authors.forename: Frederick C W
authors.initials: FC
authors.lastname: Wu
authors.affiliation: Department of Reproductive Biology, Imperial College London, London, United Kingdom.
authors.forename: Ilpo T
authors.initials: IT
authors.lastname: Huhtaniemi
authors.affiliation: Arthritis Research United Kingdom Epidemiology Unit, The University of Manchester, Manchester, United Kingdom.
authors.forename: Terence W
authors.initials: TW
authors.lastname: O'Neill
authors.affiliation: School of Community Based Medicine, The University of Manchester, Salford Royal NHS Trust, Salford, United Kingdom.
authors.forename: Neil
authors.initials: N
authors.lastname: Pendleton
authors.affiliation: Department of Andrology and Endocrinology, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Dirk
authors.initials: D
authors.lastname: Vanderschueren
authors.affiliation: Division of Developmental Medicine, Human Nutrition Section, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Michael E J
authors.initials: ME
authors.lastname: Lean
authors.affiliation: Department of Endocrinology, Royal Free and University College Hospital Medical School, Royal Free Hospital, London, United Kingdom.
authors.forename: Thang S
authors.initials: TS
authors.lastname: Han
authors.affiliation: Department of Medicine, Manchester Academic Health Science Centre, The University of Manchester, Manchester Royal Infirmary, Manchester, United Kingdom.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Finn
authors.affiliation: Department of Andrology and Reproductive Endocrinology, Medical University of Łódź, Łódź, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Kula
authors.affiliation: Clinical Physiopathology, University of Florence, Florence, Italy.
authors.forename: Gianni
authors.initials: G
authors.lastname: Forti
authors.affiliation: Department 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.
authors.forename: Felipe F
authors.initials: FF
authors.lastname: Casanueva
authors.affiliation: Department of Obstetrics, Gynecology and Andrology, University of Szeged, Szeged, Hungary.
authors.forename: György
authors.initials: G
authors.lastname: Bartfai
authors.affiliation: Andrology Unit, United Laboratories of Tartu University Clinics, Tartu, Estonia.
authors.forename: Margus
authors.initials: M
authors.lastname: Punab
authors.affiliation: Department of Clinical Sciences, Molecular Genetic Reproduction Medicine, Lund University, Malmö, Sweden.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Lundberg Giwercman
mesh_terms: D000328:Adult; D000368:Aged; D055664:Electrochemical Techniques; D005060:Europe; D005838:Genotype; D006801:Humans; D007118:Immunoassay; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017430:Prostate-Specific Antigen / Q000097:blood* / Q000235:genetics*; D011944:Receptors, Androgen / Q000235:genetics*
chemical_list: D011944:Receptors, Androgen; D017430:Prostate-Specific Antigen