Statistical Issues in the Design and Analysis of Studies of Genetic Varians HT ..

描述（由申请人提供）： 这是一份重新提交的竞争性续期申请，请求支持一个目前处于连续资助第27年的计划项目。在该计划外部咨询委员会的建议下，这次更新申请的主题从以前的广泛主题“癌症的医源性原因”缩小到更狭窄的主题“与HT和癌症有关的未解决的公共卫生问题”。“该计划有着丰富的外源激素研究历史，包括激素治疗（HT）。该计划产生的数据对药物配方，处方实践和外源性激素特别是HT使用的化学预防策略产生了重大影响。 目前申请的科学计划包括四个项目，重点围绕这一主题，由四个核心资源支持。这些项目包括：（1）HT和卵巢癌的研究，强调制剂和组织学亚型的可能风险差异;（2）HT和非霍奇金淋巴瘤（NHL）的研究，再次强调组织学亚型的可能风险差异;（3）确定哪些使用HT的妇女在乳房X线摄影密度方面发生不利变化以及这些妇女是否反过来会发展为乳腺癌的研究;以及（4）HT和癌症研究中不同测量误差来源影响的统计研究。作为该计划的一个主要重点将是评估一系列有助于HT吸收，运输和代谢的基因的潜在风险修饰效应，后一个项目还涉及与重建单倍型的识别和分析有关的统计问题。 核心资源包括一个科学领导和行政核心（核心A），负责监督科学方向和开展本方案所需的行政活动;癌症监测核心（核心B），负责提供病例识别，包括特别是项目的快速病例确定;基因分型核心（Core C），用于对涉及HT吸收、转运和代谢的大量候选基因和选定的额外基因进行基因分型;以及控制识别核心（核心D），其为所提议的项目中的两个项目提供邻域控制识别。

DESCRIPTION (provided by applicant): 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.