INHERITANCE OF DISCRETE COLORECTAL ADENOMATOUS POLYPS

离散性结直肠腺瘤性息肉的遗传

• 批准号: 3180937
• 负责人: RANDALL Walter BURT
• 金额: $ 14.96万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-01 至 1988-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3180937
• 关键词: adenocarcinoma; cancer risk; extrachromosomal DNA; gastrointestinal disorder diagnosis; gene frequency; genetic mapping; genetic markers; human population genetics; linkage mapping; neoplasm /cancer genetics

The overall objective of this proposal is to determine the role of inheritance in the development of discrete colorectal adenomatous polyps. Although colorectal cancer is believed to arise from benign adenomatus polyps, very little is known concerning the etiology of these polyps. The proposed investigation is based on the recent finding in this laboratory that discrete adenomatous polyps and colorectal cancers were inherited in a large pedigree. The purpose of this proposal is to investigate whether discrete adenomatous polyp inheritance is found in other pedigrees and to estimate the frequency with which adenomatous polyps occur on the basis of inheritance. The proposal will also investigate the suggestion from the previous study that polyp characteristics may distinguish inherited polyps in pedigrees where polyp clustering occurs. Cosegregation of adenomatous polyps and colorectal cancer will also be examined to further define the polyp cancer relationship. Blood samples will be saved for subsequent linkage studies on pedigrees which prove to be informative. The objectives of the study will be accomplished by examining the prevalence and pedigree distribution of colonic polyps and cancer in a number of pedigrees randomly ascertained on the basis of discrete adenomatous polyps found incidentally. A strict sampling scheme will be followed to avoid bias in determining mode of inheritance. Screening will include a family and medical history, stool guaiac testing, physical examination, and flexible 60 cm proctosigmoidoscopic examination. Standard statistical tests will be used for comparisons. Pedigree analysis will be performed using Pedigree Analysis Package which was developed for the analysis of complex traits. The proposed study will result in better understanding of the inheritance and pathogenesis of colonic adenomatous polyps and colorectal cancer. It will provide pedigrees with well defined phenotypes for future linkage studies. The clarification of inherited factors should also lead to improved guidelines for colorectal cancer screening in appropriate populations.

本建议的总体目标是确定 遗传在离散的结直肠腺瘤性息肉的发展中的作用。 尽管人们认为结直肠癌是由良性腺瘤引起的 关于息肉，关于这些息肉的病因学知之甚少。 的 建议的研究是基于该实验室的最新发现 分离的腺瘤性息肉和结直肠癌是遗传的， 大血统。 本建议的目的是调查是否 在其他家系中发现了离散的腺瘤性息肉遗传， 估计腺瘤性息肉发生的频率， 传承 该提案还将调查 先前的研究表明，息肉的特征可以区分遗传性息肉 在息肉聚集发生的家系中。 腺瘤性共分离 息肉和结直肠癌也将进行检查，以进一步确定 息肉癌的关系。 血液样本将保存用于后续 家系的连锁研究证明是有用的。 目标 这项研究将通过检查患病率和家系来完成 结肠息肉和结肠癌在多个家系中的随机分布 根据发现的离散腺瘤性息肉确定 顺便说一下。 将遵循严格的抽样计划，以避免偏倚， 确定继承方式。 筛选将包括一个家庭和 病史，粪便愈创木试验，体格检查，和灵活的 60 cm直肠乙状结肠镜检查。 标准统计检验将 用于比较。 将使用谱系进行谱系分析 分析包，它是为复杂性状的分析而开发的。 拟议的研究将导致更好地了解遗传 以及结肠腺瘤性息肉和结直肠癌的发病机制。 它 将为未来的连锁提供具有明确表型的谱系 问题研究 对遗传因素的澄清还应导致 改善结直肠癌筛查指南， 人口。