Abstract
ObjectiveTo investigate prostate cancer (Pca) risk in relation to estrogen metabolism, expressed as urinary 2-hydroxyestrone (2-OHE1), 16α-hydroxyestrone (16α-OHE1) and 2-OHE1 to 16α-OHE1 ratio.MethodsWe conducted a case-control study within the Western New York Health Cohort Study (WNYHCS) from 1996 to 2001. From January 2003 through September 2004, we completed the re-call and follow-up of 1092 cohort participants. Cases (n = 26) and controls (n = 110) were matched on age, race and recruitment period according to a 1:4 ratio. We used the unconditional logistic regression to compute crude and adjusted odds ratios (OR) and 95% confident interval (CI) of Pca in relation to 2-OHE1, 16αOHE1 and 2-OHE1 to 16α-OHE1 by tertiles of urine concentrations (stored in a biorepository for an average of 4 years). We identified age, race, education and body mass index as covariates. We also conducted a systematic review of the literature which revealed no additional studies, but we pooled the results from this study with those from a previously conducted case-control study using the DerSimonian-Laird random effects method.ResultsWe observed a non-significant risk reduction in the highest tertile of 2-OHE1 (OR 0.72, 95% CI 0.25-2.10). Conversely, the odds in the highest tertile of 16α-OHE1 showed a non-significant risk increase (OR 1.76 95% CI 0.62-4.98). There was a suggestion of reduced Pca risk for men in the highest tertile of 2-OHE1 to 16α-OHE1 ratio (OR 0.56, 95% CI 0.19-1.68). The pooled estimates confirmed the association between an increased Pca risk and higher urinary levels of 16α-OHE1 (third vs. first tertile: OR 1.82, 95% CI 1.09-3.05) and the protective effect of a higher 2-OHE 1 to 16α-OHE1 ratio (third vs. first tertile: OR 0.53, 95% CI 0.31-0.90).ConclusionOur study and the pooled results provide evidence for a differential role of the estrogen hydroxylation pathway in Pca development and encourage further study.
Highlights
Prostate cancer (Pca) is the most frequently diagnosed malignancy and the second leading cause of cancer death among men in Western countries [1]
In regards to Pca, experimental data from studies conducted in Noble (NBL) rats strongly suggest a critical role for estrogens in prostate carcinogenesis
In NBL rats chronically treated with testosterone, the addition of estrogens is associated with a 100% incidence of prostate adenocarcinomas, whereas the administration of testosterone as a single agent produces Pca in approximately 30 to 40% of treated animals [7,8]
Summary
Prostate cancer (Pca) is the most frequently diagnosed malignancy and the second leading cause of cancer death among men in Western countries [1]. The role played by estrogens in the pathogenesis of a wide spectrum of prostate physiologic and pathologic conditions is drawing increasing attention [6]. In regards to Pca, experimental data from studies conducted in Noble (NBL) rats strongly suggest a critical role for estrogens in prostate carcinogenesis. In NBL rats chronically treated with testosterone, the addition of estrogens is associated with a 100% incidence of prostate adenocarcinomas, whereas the administration of testosterone as a single agent produces Pca in approximately 30 to 40% of treated animals [7,8]. The estradiol plus testosterone treatment induces acinar lesions that are similar to human prostatic intraepithelial neoplasia, a well recognized pre-invasive stage of adenocarcinoma [9]
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