Urinary estrogen metabolites and prostate cancer: A case-control study in the United States

Objective: To analyze the association of prostate cancer risk with estrogen metabolism, expressed as the ratio of 2-hydroxyestrone (2-OHE1) to 16α-hydroxyestrone (16α-OHE1), in a case-control study conducted in Buffalo, NY, between 1998 and 2001. Methods: One hundred and thirteen men, aged 45-85 years, with incident, primary pathologically confirmed prostate cancer were enrolled in the study; 317 residence-matched controls were also enrolled. Cases were enrolled and the specimens collected before starting any therapy. To exclude latent prostate carcinomas, the present study included only patients with clinically apparent disease (stage B and higher). Prostate cancer cases and control subjects were excluded if on hormonal treatment, or affected with metabolic or endocrine diseases. Control subjects with a prostate-specific antigen (PSA) value higher than 4 ng/ml were excluded from the control group. Urine was used for the determinations of 2-OHE1 and 16α-OHE1. Age, race, body weight, waist-to-hip ratio, and smoking were analyzed as possible confounders. Results: Although the results were not statistically significant, elevated 2-OHE1 urinary levels suggested a reduced prostate cancer risk: men in the highest tertile had an adjusted odds ratio (OR) for prostate cancer of 0.83 (95% confidence interval (CI) 0.43-1.44). Conversely, elevated 16α-OHE1 urinary levels were associated with an increased risk of prostate cancer: the highest tertile had an adjusted OR for prostate cancer of 1.69 (95% CI 0.93-3.06, p for linear trend = 0.02). Finally, the 2-OHE1 to 16α-OHE1 ratio was associated with a reduced risk of prostate cancer with an OR of 0.61 (95% CI 0.33-1.15, p for linear trend =0.04). Conclusion: Results of this case-control study suggest that the estrogen metabolic pathway favoring 2-hydroxylation over 16α-hydroxylation may reduce risk of clinically evident prostate cancer.