Epidemiological studies related to androgens and prostate cancer have focused on serum determination of testosterone, androstenedione, and dehydroepiandrosterone, with inconsistent results. Herein, we hypothesized that differences in androgen biosynthetic and metabolic pathways, rather than differences in specific androgen concentrations, are associated with prostatic carcinogenesis. Therefore, spot urine samples from 111 incident prostate cancer cases with Gleason score at diagnosis and 227 healthy population controls, were analyzed. Urinary androgen concentrations (ng/mg creatinine) were determined by ultra-performance liquid chromatography-tandem mass spectrometry. Using a factor analysis, we identified three androgen urinary excretion patterns. In a subsample, we evaluated a modification effect of the androgen receptor CAG polymorphism. Pattern I, characterized by androstenedione and testosterone hydroxylated metabolites (11β-OHT; 2β-OHT; 15β-OHT; 2α-OHT; 6β-OHT), was associated with high prostate cancer odds among carriers of androgen receptor gene (CAG)>19 repeats (OR: 3.67 95% CI: 1.23-11.0; p for interaction=0.009). Conversely, higher testosterone excretion (pattern III), was marginally associated with lower (OR: 0.35 95% CI:0.12-1.00, p for trend=0.08) poorly differentiated prostate cancer (Gleason ≥8). No clear association was observed with pattern II (dehydroepiandrosterone; 16α and 16β-OHT). Our results were consistent with the previous evidence which suggests that the C11-oxy backdoor pathway is important for prostatic carcinogenesis. Androgen urine excretion analysis could be useful for prostate cancer diagnosis, treatment, and prognosis; however, further studies with a larger number of samples and the urinary determination of 11-ketoandrogens are necessary.
Prostate cancer (PC) is a polygenic disease with broad differences across ethnicities. BRCA1/2 and VDR have exhibited a featured genetic contribution to PC development in European populations. Nonetheless, its contribution in Latino populations specifically among Mexican men, where 70% of PC cases are detected in advanced stages, is still unknown. The contribution of seven polymorphisms in BRCA1/2 and VDR genes to PC susceptibility was evaluated in 370 incident PC cases and 759 age-matched (±5 years) controls belonging to the Mexican population. Based on Gleason score at diagnosis, PC cases were classified as well-differentiated PC (Gleason <7) and moderate or poorly differentiated PC (Gleason ≥7). Age at diagnosis was used to divided PC cases in earlier (<60 years) and late-onset PC (≥60 years). Prostate and breast cancer family histories were obtained through interview. Our results provided evidences about the contribution of BRCA1-rs1799966 (OR CC genotype = 2.30; 95% confidence interval [CI] = 1.36-3.91) to the moderate or poorly differentiated PC risk, independently of the family history of prostate, breast or ovary cancer. Further, VDR-rs2238135-G allele was associated with early-onset PC (OR G allele = 2.05; 95% CI = 1.06-3.95), and marginally with moderate or poorly differentiated PC risk. The present study revealed the crucial role of BRCA1 in PC aggressiveness risk, outstanding the gender imbalance regarding the breast cancer risk in women.
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