A Genetic Screening Policy Model for Colorectal Cancer

描述(由申请人提供)：随着我们对遗传和环境因素在结直肠癌中的作用的了解的增加，人群筛查和预防工作可以进行修改，以纳入这些信息。这项研究的目标是开发一个框架，用于评估在考虑基于基因的策略时发生的临床和经济权衡，以识别结肠癌风险增加的人。我们建议扩展现有的结直肠癌进展、筛查和诊断模型，以纳入人群中的遗传变异，以及常见基因多态和单倍型对疾病进展和发病率的影响。该模型将用于预测各种基因检测和结直肠癌筛查策略的成本效益。我们建议使用一个独特而有价值的资源-西雅图结直肠癌家庭登记(西雅图CFR)的数据来为模型提供信息。 具体目标如下： (1)(1a)通过扩展最先进的结直肠癌进展、筛查和诊断微模拟模型(MISCAN-COLON)，开发与结直肠癌风险相关的常见多态和单倍型的基因测试模型。扩展的模型将包括与基因变异相关的临床和流行病学信息，并将模拟它们对结直肠癌进展和发病率的影响。 (1B)通过将模型生成的结果与西雅图CFR中CRC病例和对照的多态/单倍型频率进行比较来验证该模型。 (2)对参加西雅图CFR的个人进行调查，以评估与多态和单倍型筛查相关的生活质量(QOL)影响，特别是考虑到测试时个人的结直肠癌个人和家族病史，以及这如何影响了解到一个人是多态携带者对生活质量的影响。假设：与那些没有变异和遗传状态未知的人相比，那些具有与CRC风险增加相关的多态/单倍型状态的人的生活质量将会降低。 (3)使用该模型，模拟各种基因检测和CRC筛查方法，以评估与结直肠癌相关的多态和单倍型人群检测替代策略的成本效益。该模型将纳入AIM 2的生活质量信息，以及西雅图CFR的家族史、临床和筛查信息。

DESCRIPTION (provided by applicant): As our knowledge of the role of genetic and environmental factors in colorectal cancer grows, population screening and prevention efforts can be modified to incorporate this information. The goal of this study is to develop a framework for evaluating the clinical and economic tradeoffs that occur when considering gene-based strategies directed towards identifying persons at increased risk for colon cancer. We propose to extend an existing model of colorectal cancer progression, screening and diagnosis to incorporate genetic variation in the population, and the impact of common genetic polymorphisms and haplotypes on disease progression and incidence. The model will be used to project the cost-effectiveness of a variety of genetic testing and colorectal cancer screening strategies. We propose to inform the model using data from a unique and valuable resource - the Colorectal Cancer Family Registry - Seattle (Seattle CFR). The specific aims are as follows: (1) (1a) Develop a model of genetic testing for common polymorphisms and haplotypes associated with CRC risk, by extending a state-of-the-art microsimulation model of colorectal cancer progression, screening and diagnosis (MISCAN-Colon). The extended model will include clinical and epidemiologic information related to genetic variants and will model their impact on colorectal cancer progression and incidence. (1b) Validate the model by comparing results generated from the model with polymorphism/haplotype frequencies among CRC cases and controls in the Seattle CFR. (2) Survey individuals enrolled in the Seattle CFR to estimate quality-of-life (QOL) effects related to polymorphism and haplotype screening, specifically considering individuals' personal and family history of colorectal cancer at the time of testing and how this influences the QOL impact of learning that one is a polymorphism carrier. Hypothesis: QOL for those with the polymorphism/haplotype state associated with increased CRC risk will be reduced, compared to those without the variant and those whose genetic status is unknown. (3) Using the model, simulate a variety of genetic testing and CRC screening approaches to estimate the cost effectiveness of alternative strategies of population testing for polymorphisms and haplotypes linked to colorectal cancer. The model will incorporate QOL information from Aim 2, along with family history, clinical, and screening information from the Seattle CFR.