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 ¼ 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 repeatlength 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. Cancer Epidemiol Biomarkers Prev; 23(10); 2048-56. Ó2014 AACR.

Does larger tumor volume explain the higher prostate specific antigen levels in black men with prostate cancer—Results from the SEARCH database

“…Another possible cause of genetic variation in PSA levels may involve single-nucleotide polymorphisms (SNP) [28–30]. A recent study by Bentmar-Holgersson et al looked at 1744 men from the European Male Ageing Study and investigated whether SNPs in the androgen receptor were associated with greater PSA values [28].…”

“…A recent study by Bentmar-Holgersson et al looked at 1744 men from the European Male Ageing Study and investigated whether SNPs in the androgen receptor were associated with greater PSA values [28]. They found that patients with SNP rs1204038 A-allele had a 65% higher risk of PSA>3 ng/mL compared to G-allele carriers.…”

The androgen receptor gene CAG repeat in relation to 4-year changes in androgen-sensitive endpoints in community-dwelling older European men

“…In contrast, Van Pottelbergh and co-workers did not observe an association between the AR CAG repeat and androgen levels, androgen insensitivity index (LH × TT product) or bone markers within a cross-sectional cohort study consisting of ambulatory elderly men (16). In addition, Bentmar-Holgersson and co-workers (17) did not observe an association between the AR CAG repeat and PSA levels or prostate cancer risk within cross-sectional data from the European Male Ageing Study (EMAS). However, additional cross-sectional results from EMAS have led Huhtaniemi and colleagues (18) to propose that the potential downstream consequences of longer AR CAG repeat length and the concomitant decreased androgen action may be modified by compensatory increased oestradiol (E 2 ) levels.…”