INHERITANCE OF DISCRETE COLORECTAL ADENOMATOUS POLYPS

离散性结直肠腺瘤性息肉的遗传

• 批准号: 3180939
• 负责人: RANDALL Walter BURT
• 金额: $ 18.83万
• 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 1991-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3180939
• 关键词: adenoma; alleles; cancer risk; extrachromosomal DNA; gastrointestinal disorder diagnosis; gene frequency; genetic mapping; genetic markers; human population genetics; human subject; linkage mapping; molecular oncology; neoplasm /cancer diagnosis; neoplasm /cancer genetics; preneoplastic state

The objective of this proposal is to investigate the inheritance of discrete colonic adenomatous polyps and colorectal cancer. Present investigation provides evidence that the majority of commonly occurring adenomatous polyps are found in individuals with an inherited susceptibility to polyp formation. Because colon cancer develops from adenomatous polyps, this finding suggests that randomly occurring colorectal cancers likewise occur in those who are genetically susceptible. The specific aims of the proposal are therefore to test the hypothesis that inheritance plays an important role in the development of randomly occurring colorectal cancers; and to verify, characterize and refine the initial findings of adenomatous polyp inheritance. To examine the hypothesis of colon cancer inheritance, the occurrence and pedigree distribution of adenomatous polyps will be determined in family members of pedigrees systematically selected on the basis of a single individual with colorectal cancer. Adenomas are detected by 60 cm flexible proctosigmoidoscopy. Pedigree analysis which employs likelihood methods will be used to evaluate the presence of inherited susceptibility to colonic polyps and cancer. These results will be compared to the adenoma inheritance which has been observed in pedigrees selected on the basis of an individual with an adenomatous polyp, and in pedigrees selected on the basis of a sibling pair with colorectal cancer. Additional pedigrees in each of these selection categories will also be examined to substantiate observed polyp characteristic differences between the groups. Larger study sizes are likewise required to refine estimates of population gene frequencies, to improve confidence limits of estimates and to more rigorously test inheritance mode. A final aim of the investigation is to collect blood for anticipated DNA mapping studies. The delineation of inherited susceptibility to common colonic polyps and cancer is expected to impact clinical cancer screening efforts significantly. The population characterized by this study will also provide the basis for DNA marker linkage studies, subsequent studies of gene-environment interactions, and studies of molecular mechanisms of cancer.

这项提案的目的是调查遗产 结肠腺瘤性息肉和结直肠癌的发病率。 目前的调查表明，大多数 通常发生的腺瘤性息肉发现于患有 对息肉形成的遗传易感性。 因为结肠 癌症是从腺瘤性息肉发展而来的，这一发现表明， 随机发生的结直肠癌同样发生在那些 是遗传易感的。 该提案的具体目标是 因此，为了检验遗传在 在随机发生的结直肠癌的发展中起重要作用 癌症;并核实，表征和完善最初的 腺瘤性息肉的遗传表现。 为了检验结肠癌遗传的假设， 腺瘤性息肉的发生率和谱系分布， 在系统选择的家系成员中确定 是基于一个结直肠癌的个体。 腺瘤通过60 cm柔性直肠乙状结肠镜检查发现。 采用似然方法的谱系分析将用于 评估是否存在结肠息肉的遗传易感性 和癌症 这些结果将与腺瘤进行比较 遗传，这已被观察到的家系选择上的 腺瘤性息肉个体的基础和家系 根据患有结直肠癌的同胞配对进行选择。 在这些选择类别中的每一个额外的谱系将 还应检查以证实观察到的息肉特征 群体之间的差异。 更大规模的研究同样 需要完善人口基因频率的估计， 提高估计置信限，并更严格地检验 继承模式 调查的最终目的是收集 血液用于预期的DNA图谱研究 大肠癌遗传易感性的描述 息肉和癌症有望影响临床癌症筛查 的重大努力。 本研究所描述的人群 也将为DNA标记连锁研究提供基础， 基因与环境相互作用的后续研究， 癌症的分子机制。