This proposal is designed to provide the applicant, Dr. Gloria Mao, with the scientific skills and career development necessary for a successful academic career in cancer prevention and control research. Together, with a targeted program of didactic instruction, guided mentorship, collaborative research, and participation in national meetings, this project will prepare the applicant to become a fully independent scientist. A molecular epidemiology study is proposed to characterize the role of the retinoid receptors in prostate carcinogenesis. The retinoic acid receptors, RARs, and the retinoid X receptors, RXRs, mediate the anticarcinogenic effects of retinoic acid. Prostate tissue, pathology records and a life-style/exposures questionnaire have been obtained from 118 prostate cancer cases and 102 bladder cancer cases that may serve as controls in this study. The specific aims of the study are: (1) measure the RARs and RXRs at different levels of expression regulation: mRNA and protein levels and RARbeta promoter methylation in paired prostate tissue containing normal prostate, prostatic intraepithelial neoplasia, and adenocarcinoma; (2) measure the correlations between molecular alterations in the retinoid receptors with clinical and pathological variables including tumor stage, grade, and patient survival; (3) measure the correlations between RARa promoter methylation and RARbeta mRNA and protein levels; (4) evaluate the strength of the associations between molecular alterations in the RARs and RXRs with patient demographics, environmental exposures, dietary factors and serum micronutrient levels. Differential expression of specific retinoid receptors and hypermethylation of the RARbeta promoter are hypothesized to exist between normal, PIN and adenocarcinoma. An assessment of whether retinoid receptor molecular alterations are useful biological markers of prostate cancer progression will be made. The strength of the associations between retinoid receptor status with environmental and dietary exposures may be used to identify potential gene-risk factor interactions for prostate cancer.