) This proposal is designed to build upon ongoing studies evaluating epidemiologic and molecular determinants of clinical prostate cancer (PC) susceptibility being conducted at the UT MD Anderson Cancer Center (CA 68578 M. Spitz, M.D., Principal Investigator, DAMD 17-98-1-8471 S.Strom, Ph.D., Principal Investigator. A role for individual variability in androgen biosynthesis as a modifier of PC risk is under intensive investigation. Based on the fact that catecholamines act synergistically with androgens through beta-adrenergic receptors as important regulators of prostate growth and differentiation, we present a novel hypothesis that individual genetic differences in the beta-adrenergic receptor may be associated with PC risk. Specifically, we will determine whether common allelic variants in beta-adrenergic gene modify the risk of developing prostate cancer. By integrating these genotypic data with information on diet, body composition, co-morbid conditions, and other lifestyle characteristics known to alter testosterone levels, we will gain insight into the role that individual variability in the neuroendocrine control of prostate growth plays in PC risk. The proposed pilot epidemiologic study will be the first of which we are aware to examine the contribution of gene-based variability in the beta-adrenergic response and risk of developing prostate cancer. Correlation of markers with PC risk in this pilot or hypothesis generating study would provide the impetus to pursue further the role of neuroendocrine factors in the etiology and progression of PC.
