Research Article Androgen Receptor Polymorphism-Dependent Variation in Prostate-Specific Antigen Concentrations of European Men

Background: Androgens acting via the androgen receptor (AR) stimulate production of PSA, which is a clinical marker of prostate cancer. Because genetic variants in theARmay have a significant impact on the risk of being diagnosed with prostate cancer, the aimwas to investigate whether AR variants were associated with the risk of having PSA above clinically used cutoff thresholds of 3 or 4 ng/mL inmenwithout 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) thanG-allele carriers. They also had shorterCAG repeats (median 20 vs. 23,P < 0.0005), butCAG repeat length per se did not affect the PSA concentrations. Conclusion:TheA-allele of the SNP rs1204038gives a 65%higher risk of havingPSAabove 3ng/mL than the G-allele inmenwithout prostate cancer, and thereby an increased risk of being referred for further examination on suspicion of prostate cancer. Impact: SerumPSAas a clinicalmarker could be improved by adjustment forAR-genotype.Cancer Epidemiol Biomarkers Prev; 23(10); 1–9. 2014 AACR