FAMILIAL COLORECTAL NEOPLASIA COLLABORATIVE GROUP

描述：（申请人的描述） 大肠腺癌仍然是一个重要的公众 健康问题，在癌症死亡原因中居第二位， 占所有癌症的10%。 早期发现现在被认为是 是影响结直肠癌预后的重要因素之一。 目前可用的有助于早期发现的筛查方式包括 或者对于一般人群筛查（结肠镜检查）非常昂贵，或者 疾病检测的灵敏度和特异性低（粪便潜血 测试）。 为了显著影响结直肠癌死亡率，工具 需要提高了解哪些人口成员的能力 值得积极筛选，或者替代地，需要成本高的工具， 有效但高度敏感，例如检测癌前病变的测试 粪便中脱落的结肠细胞的遗传改变。 一个有希望的战略， 研究家庭的方法是， 结直肠癌的发病率。 这些家庭，沿着着精心挑选的 控制，将允许检查遗传和环境因素 易患结直肠癌 虽然取得了重大进展， 在确定遗传性结肠中不常见的高突变率基因方面取得了进展， 癌症，低突变基因或环境因素的鉴定 这可能占大多数家族性结直肠癌将需要 研究了大量仔细确定的家庭。 响应于 国家癌症研究所呼吁建立一个合作家庭登记处， 结肠癌的流行病学研究，申请人提出了一种方法， 将对5,000名结直肠癌先证者进行家庭调查， 历史，并从该组中选出500个高风险家庭， 进一步招聘。 登记册的家庭招募将涉及 收集临床和流行病学数据，加上收集生物学数据， 标本包括血液和肿瘤。 类似的确定将是 对病例匹配对照和结直肠癌人群进行 对照 来自病例和对照的肿瘤标本将被 关于错配修复蛋白的表达，其特征在于， 通过免疫组织化学测定。 此应用程序用于协作 开发可提供高质量数据的持久资源， 生物材料的最有前途的研究工作， 降低结直肠癌死亡率。

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.