FAMILIAL COLORECTAL NEOPLASIA COLLABORATIVE GROUP

产品说明：（申请人的描述）大肠腺癌仍然是一个重要的公共健康问题，作为癌症导致的死亡原因排名第二，占所有癌症的10%。早期发现现在被认为是结直肠癌预后的最重要因素之一。目前可用的筛查模式，促进早期检测要么是非常昂贵的一般人群筛查（结肠镜检查）或具有较低的灵敏度和特异性的疾病检测（粪便潜血试验）。 为了显著影响结直肠癌死亡率，需要提高了解哪些人群成员值得进行积极筛查的能力的工具，或者需要具有成本效益但高度敏感的工具，例如检测粪便中脱落的结肠细胞中癌前基因改变的测试。 实现这些目标的一个有希望的策略是研究结直肠癌发病率增加的家庭。 这些家庭，沿着精心挑选的对照，将允许检查遗传和环境因素诱发结直肠癌。 虽然在确定遗传性结肠癌中不常见的高突变率基因方面已经取得了重大进展，但要确定可能导致大多数家族性结肠直肠癌的低突变率基因或环境因素，还需要对大量仔细确定的家族进行研究。为了响应国家癌症研究所对结肠癌流行病学研究合作家庭登记处的呼吁，申请人提出了一种方法，其中将调查5，000名结肠直肠癌先证者的家族史，并从该组中选择500个高风险家庭用于进一步招募。登记研究的家庭招募将包括收集临床和流行病学数据，以及收集生物标本，包括血液和肿瘤。将对病例匹配对照组和结直肠癌人群对照组进行类似的确定。 将通过免疫组织化学测定的错配修复蛋白的表达来表征来自病例和对照的肿瘤标本。 该应用程序是一个持久的资源，将提供高质量的数据和生物材料，以最有前途的研究工作，旨在降低结直肠癌死亡率的合作开发。

DESCRIPTION: (Applicant's Description) Adenocarcinoma of the large bowel continues to be a significant public health problem, ranking second as a cause of death due to cancer and representing 10 percent of all cancers. Early detection is now recognized as one of the most important factors in colorectal cancer prognosis. Currently available screening modalities that facilitate early detection are either very costly for general population screening (colonoscopy) or have low sensitivity and specificity for disease detection (fecal occult blood testing). To significantly impact colorectal cancer mortality rates, tools are needed that improve the ability to know which members of the population merit aggressive screening, or alternatively, tools are needed that are cost effective yet highly sensitive, such as tests that detect precancerous genetic alterations in colonocytes shed in stool. A promising strategy to move toward these goals is that of studying families that have had increased rates of colorectal cancer. These families, along with carefully selected controls, will permit examination of the genetic and environmental factors predisposing to colorectal cancer. Although significant progress has been made in identifying the uncommon, high penetrance genes in hereditary colon cancers, the identification of low penetrance genes or environmental factors that may account for the majority of familial colorectal cancer will require studies of large numbers of carefully ascertained families. In response to the National Cancer Institute's call for a Cooperative Family Registry for Epidemiologic Studies of Colon Cancer, the applicant proposes a process whereby 5,000 colorectal cancer probands will be surveyed for family history, and from this group 500 high risk families will be selected for further recruitment. Family recruitment for the registry will involve collection of clinical and epidemiologic data, plus collection of biologic specimens including blood and tumor. Similar ascertainment will be undertaken for both case- matched controls and colorectal cancer population controls. Tumor specimens from both cases and controls will be characterized with respect to expression of mismatch repair proteins as determined by immunohistochemistry. This application is for collaborative development of a durable resource that will provide high quality data and biologic materials to the most promising research efforts directed toward decreasing colorectal cancer mortality.