INHERITANCE OF DISCRETE COLORECTAL ADENOMATOUS POLYPS

这项提议的目的是调查遗产 散发性结肠腺瘤性息肉和结直肠癌。 目前的调查提供的证据表明，大多数 常见的腺瘤性息肉可见于患有 对息肉形成的遗传易感性。因为冒号 癌症由腺瘤性息肉发展而来，这一发现表明 随机发生的结直肠癌同样发生在那些 都是遗传易感的。这项提议的具体目的是 因此，要检验继承对 在随机发生的结直肠癌发展中的重要作用 癌症；并核实、描述和提炼首字母 腺瘤性息肉遗传的表现。 为了检验结肠癌遗传的假说， 腺瘤性息肉的发生和家系分布将是 在系统选择的家系成员中确定 基于一名患有结直肠癌的个体。 腺瘤由60厘米长的柔性直肠乙状结肠镜检查。 使用似然方法的系谱分析将被用于 评估遗传性结肠息肉易感性的存在 和癌症。这些结果将与腺瘤进行比较。 在家系中观察到的遗传 腺瘤性息肉的个体基础和家系 是根据结直肠癌同胞配对选择的。 这些选择类别中的其他谱系将 也要检查以证实观察到的息肉特征 不同群体之间的差异。更大的研究规模也是如此 需要完善对群体基因频率的估计，以 提高估计的置信限，并进行更严格的检验 继承模式。调查的最终目的是收集 用于预期DNA图谱研究的血液。 遗传性普通结肠易感性的研究进展 息肉和癌症预计将影响临床癌症筛查 显著的努力。这项研究所描述的人群 也将为DNA标记连锁研究提供基础， 基因-环境相互作用的后续研究，以及研究 癌症的分子机制。

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.