FAMILIAL FACTORS IN THE DEVELOPMENT OF COLON AND OTHER CANCERS

该建议基于以下假设：结肠直肠癌（CRC）和其他癌症主要发生在高危人群中，该人群由携带特定基因定义，这些基因赋予腺瘤性结肠息肉形成的易感性。 此外，识别这组个体将导致通过靶向和筛选那些处于最大风险的个体来降低CRC死亡率的成本有效的策略。 CRC发生的遗传易感性已得到广泛认可。 虽然大多数结肠癌和其他癌症是散发性的，但人们越来越认识到，很大一部分癌症是由于遗传易感性。 众所周知，一些已知的结肠癌易感基因的种系突变赋予早发性结肠肿瘤的显著风险。 该项目的最终目标是测试结肠息肉形成的易感性由主要易感等位基因决定的预测。 本研究的目的是：（1）建立一个由300对成年同胞组成的队列，这些同胞患有结肠息肉和/或结肠癌;（2）对多达600对同胞进行乙状结肠镜检查，以确定结肠息肉的存在或不存在;（3）收集全血用于DNA提取、WBC储存和血清储存;（4）为少数结肠息肉易感性候选基因位点开发多态性标记作为试点项目。

This proposal is based on the hypothesis that colorectal cancer (CRC) and other cancers principally occur in a high risk group that is defined by the carriage of specific genes that confer susceptibility to formation of adenomatous colon polyps. Additionally, identification of this group of individuals would lead to a cost effective strategy for reducing CRC mortality by targeting and screening those individuals who are at greatest risk. Genetic susceptibility for the development of CRC is well recognized. While the majority of colon and other cancers are sporadic, there is growing recognition that a significant proportion of cancer is due to inherited susceptibility. It is well established that germline mutations of some of the already known colon cancer susceptibility genes confer a marked risk of early onset colon neoplasia. The ultimate goal of this project is to test the prediction that susceptibility to colon polyp formation is determined by a major susceptibility allele. The goals of the study are (1) to develop a cohort of 300 adult sibling pairs who are concordant for either colon polyps and/or colon cancer; (2) to perform flexible sigmoidoscopy on up to 600 siblings to determine the presence or absence of colon polyps; (3) to collect whole blood for DNA extraction, WBC storage, and serum storage; and (4) to develop polymorphic markers as a pilot project for a small number of candidate gene loci for colon polyp susceptibility.