The estradiol plus testosterone treatment also induces acinar lesions that are similar to human prostatic intraepithelial neoplasia, a well recognized pre-invasive stage of adenocarcinoma [9]. Evidence is also mounting regarding the contribution of hydroxylated metabolites of estrone (E1) and estradiol (E2) to the overall

estrogenic activity. The mutually exclusive hydroxylation of E1 and E2 at positions C-16α or C-2 leads to the production of either biologically active estrogens (16α-hydroxyestrone/estradiol) or derivatives 3-Methyladenine chemical structure with virtually no estrogenic activity (2-hydroxyestrone/estradiol), respectively [10–12]. The different profiles in terms of biological activity and genotoxic properties might have consequences

Linsitinib in vitro in terms of Pca risk. However, the overall body of evidence Osimertinib manufacturer remains particularly limited when considering estrogen metabolites in relation to Pca risk. Our prior case-control study, conducted in Buffalo, NY, suggested an increased risk of clinically evident Pca in men with a lower 2-OHE1/16α-OHE1 ratio [13]. Similar results from studies evaluating breast cancer, as another hormone-dependent tumor, support this observation [14–18]. In the current case-control study, we have further tested the hypothesis that the pathway favoring 2-hydroxylation over 16α-hydroxylation is associated with a reduction in Pca risk. from We also conducted a systematic review of the literature to evaluate the totality of the evidence of this research question. Material and methods From 1996 to 2001, 1961 men were enrolled in the Western New York Health Cohort Study (WNYHCS). A detailed description of the WNYHCS study design, methods and participants’ characteristics is available elsewhere [14]. In brief, all participants provided informed consent; the Human Subjects Review Board of the University at Buffalo, School of Medicine and Biomedical Science approved procedures for protection of human subjects in the study. At the time of recruitment, trained interviewers collected extensive data on demographics and life style during in-person

interviews. The use of a standardized protocol allowed for the collection of anthropometric data. The study participants donated morning spot urine which was kept at -80°C until biochemical determinations. From January 2003 through September 2004, we completed the Western New York Health Cohort (WNYHC) re-call and follow-up. For the purposes of the present case-control study (PROMEN II study), the re-call process included male participants who met the following inclusion criteria: age at recruitment between 50 and 85, baseline history negative for malignancies, cardiovascular diseases and clinically defined type-2 diabetes. On this basis, the re-call and follow-up process involved 1092 cohort participants.