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签申请，请求对目前处于连续资助第27年的计划项目提供支持。在该计划外部咨询委员会的建议下，这次续签申请的主题从以前的广泛主题“癌症的致病原因”缩小到更狭隘的主题“与高血压和癌症有关的悬而未决的公共卫生问题”。该计划在包括激素治疗(HT)在内的外源激素研究方面有着丰富的历史。该计划产生的数据对药物配方、处方实践和有关外源性激素特别是羟色胺使用的化学预防策略产生了重大影响。 本次申请的科学计划由四个围绕这一主题的项目组成，由四个核心资源提供支持。这些项目包括：(1)对羟色胺和卵巢癌的研究，强调在配方和组织学亚型方面可能存在的风险差异；(2)对羟色胺和非霍奇金淋巴瘤(NHL)的研究，同样侧重于根据组织学亚型可能存在的风险差异；(3)研究，以确定哪些使用羟色胺的女性会出现乳房摄影密度的不利变化，以及这些女性是否会患乳腺癌；以及(4)对不同测量误差来源的影响在甲状腺激素和癌症研究中的影响的统计研究。由于该计划的主要重点将是评估一系列与羟色胺的吸收、运输和代谢有关的基因的潜在风险调节效应，后一个项目还涉及与识别和分析重建的单倍型有关的统计问题。 核心资源包括一个科学领导和行政核心(核心A)，负责监督科学指导和进行本计划要求的行政活动；癌症监测核心(核心B)，提供病例识别，包括为项目提供特别快速的病例确定；基因分型核心(核心C)，用于对一大系列与羟色胺吸收、运输和新陈代谢有关的候选基因和选定的额外基因进行基因分型；以及对照识别核心(核心D)，用于为拟议的两个项目提供邻里控制识别。

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.