This is a resubmission of a competing renewal application requesting support for a Program Project currently in its 27th year of continuous funding. At the recommendation of the Program's External Advisory committee, the theme of this renewal application was narrowed from the previous broad theme of """"""""latrogenic Causes of Cancer"""""""" to a more narrow theme of """"""""Unresolved Public Health Issues Related to HT and Cancer."""""""" The Program has a rich history of research on exogenous hormones including hormone therapy (HT). Data generated from the Program have had major influences on pharmaceutical formulations, prescribing practices, and chemoprevention strategies regarding exogenous hormone especially HT use. The scientific program of the current application consists of four projects focused around this theme supported by four core resources. The projects include: (1) a study of HT and ovarian cancer emphasizing possible risk differences in formulations and histologic subtypes; (2) a study of HT and non-Hodgkin's lymphomas (NHL), again with an emphasis on possible risk differences by histologic subtypes; (3) a study to determine which women who use HT develop adverse changes in mammographic densities and whether these are the women, in turn, who will develop breast cancer; and (4) a statistical study of the impact of different sources of measurement error in studies of HT and cancer. As a major emphasis of the Program will be to evaluate the potential risk modifying effects of a series of genes contributing to absorption, transport and metabolism of HT, this latter project also deals with statistical issues related to identification and analysis of reconstructed haplotypes. Core resources include a Scientific Leadership and Administrative Core (Core A) for overseeing scientific direction and conducting the administrative activities required by this Program; the Cancer Surveillance Core (Core B), which provides case identification, including especially rapid case ascertainment for the projects; a Genotyping Core (Core C), for genotyping a large series of candidate genes involved in HT absorption, transport and metabolism and selected additional genes; and a Control Identification Core (Core D), which provides neighborhood control identification for two of the proposed projects.
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