GENETIC PREDISPOSITION TESTING IN COLORECTAL CANCER

结直肠癌的遗传易感性检测

• 批准号: 6164129
• 负责人: Deborah Schrag
• 金额: $ 13.09万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-03-20 至 2004-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6164129
• 关键词: Jewish; adenomatous polyps; cancer prevention; cancer risk; clinical research; colorectal neoplasms; family genetics; gene frequency; gene mutation; genetic screening; genetic susceptibility; health care cost /financing; human genetic material tag; human population genetics; human subject; neoplasm /cancer classification /staging; neoplasm /cancer genetics; quality of life; racial /ethnic difference; Jewish; adenomatous polyps; cancer prevention; cancer risk; clinical research; colorectal neoplasms; family genetics; gene frequency; gene mutation; genetic screening; genetic susceptibility; health care cost /financing; human genetic material tag; human population genetics; human subject; neoplasm /cancer classification /staging; neoplasm /cancer genetics; quality of life; racial /ethnic difference

The explosion of genetic technology makes identification of individuals with increased cancer risks possible and creates the potential to target cancer screening and prevention efforts. However, the circumstances where genetic predisposition testing is actually an effective and cost-effective clinical strategy are uncertain. A recently described low-penetrance germline mutation in codon I1307K of the APC gene that appears to increase colorectal cancer risk among Ashkenazi Jews underscores the need to critically evaluate when and how genetic testing strategies should be incorporated into clinical cancer prevention. We propose a genetic epidemiologic study among Ashkenazi patients with colorectal cancer and polyps that evaluates the significance of I1307K APC mutations. Our findings will be used to construct a decision analysis model that provides a comprehensive framework for predicting the clinical importance and policy implications of predictive testing for this as well as for other colon cancer predisposing genes. The specific aims to accomplish these goals are: 1. To determine the significance of inherited I1307K APC mutations in a hospital-based cohort of American and Israeli Ashkenazi Jews with colorectal cancer or adenomatous polyps. By evaluating gene frequency and penetrance, this analysis will assess the extent to which inherited I1307K APC mutations increase cancer risk and whether mutation-associated tumors have particular prognostic features. 2. To assess the effectiveness, measured in life-years and quality-adjusted life years, and the cost-effectiveness, of genetic testing for inherited colorectal cancer susceptibility. In particular, we will examine the impact of gene penetrance, gene frequency, age, family history, test characteristics, associated costs, and knowledge motivated screening compliance on the cost-effectiveness of genetic testing strategies. Faculty sponsors in the Division of Population Sciences at the Dana-Farber Cancer Institute will provide the candidate with the guidance critical to accomplishing these aims and to attaining independence as an investigator focused on evaluating the application of genetic technologies to cancer prevention.

遗传技术的爆炸使人们确定癌症风险增加的个体成为可能，并创造了针对癌症筛查和预防工作的潜力。但是，遗传倾向测试实际上是一种有效且具有成本效益的临床策略的情况。 最近描述的APC基因I1307K中的低渗透性种系突变似乎增加了Ashkenazi犹太人中结直肠癌风险的风险，强调了需要评估何时以及如何将基因测试策略纳入临床癌症预防中。 我们提出了在结直肠癌和息肉患者中进行遗传流行病学研究，该研究评估了I1307K APC突变的重要性。 我们的发现将用于构建一个决策分析模型，该模型提供了一个全面的框架，以预测对此预测性测试以及其他结肠癌的临床重要性和政策含义。 实现这些目标的具体目的是：1。确定遗传的I1307K APC突变在医院基于医院的美国和以色列Ashkenazi犹太人患有结直肠癌或腺瘤息肉的同类中。通过评估基因频率和外观，该分析将评估遗传的I1307K APC突变的程度增加癌症的风险以及突变相关的肿瘤是否具有特殊的预后特征。 2。为了评估在生命年和质量调整的寿命中衡量的有效性，以及对遗传性结直肠癌易感性的基因检测的成本效益。 特别是，我们将研究基因渗透率，基因频率，年龄，家族史，测试特征，相关成本和知识的影响，以筛查基因测试策略的成本效益。达纳 - 法伯癌症研究所（Dana-Farber Cancer Institute）的人口科学划分的教师赞助者将为候选人提供至关重要的指导，这对于实现这些目标和实现独立性至关重要，因为研究人员致力于评估遗传技术在预防癌症预防中的应用。