FAMILIAL COLORECTAL NEOPLASIA COLLABORATIVE GROUP

描述：(申请人描述)结肠腺癌仍然是一个重要的公共卫生问题，排在癌症死亡原因的第二位，占所有癌症的10%。早期发现是影响结直肠癌预后的重要因素之一。目前，有助于早期发现的现有筛查方式要么对普通人群筛查(结肠镜检查)非常昂贵，要么对疾病检测(粪便潜血测试)的敏感性和特异性较低。为了显著影响结直肠癌死亡率，需要提高了解人群中哪些成员需要积极筛查的能力，或者需要成本效益高但高度敏感的工具，例如检测粪便中结肠细胞中的癌前基因变化的测试。迈向这些目标的一个有希望的策略是研究那些结直肠癌发病率增加的家庭。这些家系，加上精心挑选的对照，将允许对易患结直肠癌的遗传和环境因素进行检查。尽管在确定遗传性结肠癌中不常见的高外显性基因方面取得了重大进展，但要确定可能导致大多数家族性结直肠癌的低外显性基因或环境因素，仍需要对大量仔细确定的家系进行研究。为了响应国家癌症研究所呼吁建立结肠癌流行病学研究合作家庭登记处的呼吁，申请人提出了一项程序，将对5,000名结直肠癌先证者进行家族史调查，并从这一组中挑选500个高危家庭进行进一步招募。登记的家庭招募将包括收集临床和流行病学数据，以及收集包括血液和肿瘤在内的生物标本。将对病例配对对照和结直肠癌人群对照进行类似的确定。病例和对照的肿瘤标本将通过免疫组织化学方法确定错配修复蛋白的表达特征。这项应用是为了合作开发一种持久的资源，为旨在降低结直肠癌死亡率的最有希望的研究努力提供高质量的数据和生物材料。

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.