Methods for Statistical Analysis of Cancer Genetic Network Studies

描述(由申请人提供)： 美国国家癌症研究所(NCI)于1998年建立了癌症遗传学网络(CGN)，这是一个多中心的国家项目，旨在支持对癌症易感性的遗传基础进行合作调查，并探索将这一新知识整合到医疗实践中的机制。这一高危人群的一个根本问题是如何以最佳方式进行筛查，以便及早发现疾病。最近发现的新的生物标记物会随着疾病的早期阶段而变化，这为筛查提供了有希望的非侵入性策略。然而，确定最佳策略的两个基本方面是：什么癌症是高风险个体，以及如何使用生物标记物上的纵向测量来预测疾病风险。为了在癌症遗传学网络项目的背景下关注这些问题，这项提案有两个目的。第一个目标是开发和应用分析家族史数据的方法，以发现哪些癌症倾向于聚集在个人和家庭中。我们将制定可应用于CGN登记(家族史)数据的方法，并适当考虑参与者的年龄和确定方式。我们将应用这些方法来识别在家庭中一起发生的癌症部位集群。这项建议的第二个目标是开发和应用一种方法来评估纵向收集的生物标记物与疾病发病的早期证据之间的关系。该方法将使我们能够分析CGN卵巢癌(CA125)生物标记物筛查研究的数据，因为它将适当地处理这些纵向和事件时间数据，即使这些妇女的筛查计划因错过或延误就诊而改变。这项提案的PI是癌症遗传学网络统计协调中心的PI，负责监督CGN研究的数据收集和分析，但不资助统计方法研究。这笔赠款将提供完成研究和应用所需统计方法所需的支助。这项研究有可能对有癌症家族史的脆弱人群产生重大影响，因为它将使筛查战略更专注于个人风险较高的癌症，并有可能提高疾病在可治疗阶段被发现的机会。

DESCRIPTION (provided by applicant): The National Cancer Institute (NCI) established the Cancer Genetics Network (CGN) in 1998 as a multi-centered national project designed to support collaborative investigations on the genetic basis of cancer susceptibility and to explore mechanisms to integrate this new knowledge into medical practice. A fundamental issue in this high-risk population is how to optimally screen for early detection of disease. Recent discovery of new biomarkers that change with early stages of disease offer promising non-invasive strategies for screening. However, two aspects that are fundamental for determining an optimal strategy are: for what cancers is the individual at elevated risk and how can longitudinal measurements on a biomarker be used to predict risk of disease. To focus on these issues in the context of the Cancer Genetics Network project, there are two aims in this proposal. The first aim will develop and apply methods for analyzing data on family history to discover what cancers tend to aggregate in individuals and families. We will develop methodology that can be applied to the CGN Registry (family history) data and appropriately accounts for age and mode of ascertainment of participants. We will apply these methods to identify clusters of cancer sites that occur together in families. The second aim of this proposal focuses on the development and application of a method to assess the relationship between longitudinally collected biomarkers and early evidence of disease onset. The method will allow us to analyze data from the CGN Ovarian Cancer (CA125) Biomarker Screening study, as it will appropriately handle this longitudinal and event time data even though the screening schedule for these women varied due to missed or delayed visits. The PI of this proposal is the PI on the Statistical Coordinating Center of the Cancer Genetics Network, and is responsible for overseeing data acquisition and analysis of CGN studies, but is not funded for statistical methods research. This grant would provide the support needed to complete the research for and apply the required statistical methods. This research has the potential of a major impact on the vulnerable population of individuals with family history of cancer, as it will allow the screening strategy to be more focused on cancers to which the individual is at elevated risk, and potentially improve the chances that the disease will be detected in a treatable stage.