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，可以修改人群筛查和预防工作以纳入这些信息。本研究的目的是开发一个框架，用于评估临床和经济权衡时发生的考虑基因为基础的策略，旨在确定人在结肠癌的风险增加。我们建议扩展结直肠癌进展、筛查和诊断的现有模型，以纳入人群中的遗传变异，以及常见遗传多态性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。我们建议使用来自独特且有价值的资源-结直肠癌家族登记处-西雅图（西雅图CFR）的数据来告知模型。 具体目标如下： (1)（1a）通过扩展结肠直肠癌进展、筛查和诊断的最新微观模拟模型（MISCAN-Colon），开发与CRC风险相关的常见多态性和单倍型的基因检测模型。扩展模型将包括与遗传变异相关的临床和流行病学信息，并将模拟其对结直肠癌进展和发病率的影响。 (1b)通过比较模型产生的结果与西雅图CFR中CRC病例和对照之间的多态性/单倍型频率来验证模型。 (2)对参加西雅图CFR的个体进行调查，以评估与多态性和单倍型筛查相关的生活质量（QOL）影响，特别是考虑个体在检测时的结直肠癌个人和家族史，以及这如何影响了解一个人是多态性携带者的QOL影响。假设：与那些没有变异的人和那些遗传状态未知的人相比，具有与CRC风险增加相关的多态性/单倍型状态的人的QOL将降低。 (3)使用该模型，模拟各种基因检测和CRC筛查方法，以估计与结直肠癌相关的多态性和单体型群体检测的替代策略的成本效益。该模型将纳入来自Aim 2的QOL信息，沿着来自西雅图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.