GENETIC EPIDEMIOLOGY OF CANCER AND PREDISPOSING LESIONS

过去二十年在分子生物学和科学领域的科学革命 计算机科学已经为极大地增加我们的 对癌症病因学的理解。在这个计划项目中，我们利用 从这些领域衍生出来的方法来研究三种常见的 癌症及其前驱病变：1)腺瘤性息肉和结肠癌 癌症，2)发育不良的痣和黑色素瘤，以及3)增生性乳房疾病 和乳腺癌。该方案项目的基本主题是 分析常见癌症的前驱病变是确定 了解他们的病因。家族聚集性疾病是一种主要的 项目的重点；它们允许对基因进行详细分析 易感性，提供了基因图谱的基础，并提供了高风险 对其他危险因素进行分析。研究的细节 每种特性的项目根据我们目前的理解水平而有所不同， 但所有三项研究都有三个共同目标，包括：1) 常见癌症前驱病变的定义和基因分析。2) 影响基因表达的遗传和环境因素分析 以及3)影响前兆表型的因素分析。 前驱病变转化为恶性病变。累积起来，这些 研究相当于对基因类型描述的不断完善 易感基因座。我们已经取得了相当大的进展， 结肠癌和黑色素瘤的前驱病变，尽管这些描述 将通过项目得到极大的推动。关于遗传前体的定义 对于乳腺癌来说，还处于初级阶段。通过研究具有 对前体的表型和作用的不同水平的知识，我们 能够迅速将在一个项目中获得的经验应用到其他项目中 所有项目共有的基础设施。

The scientific revolutions of the last two decades in molecular biology and computer science have created the basis for greatly increasing our understanding of cancer etiology. In this program project we utilize approaches derived from these fields to study the etiology of three common cancers and their precursor lesions: 1) the adenomatous polyp and colon cancer, 2) dysplastic nevi and melanoma, and 3) proliferative breast disease and breast cancer. The underlying theme of the program project is that the analysis of precursor lesions to common cancers is a major key to understanding their etiology. Familial clusters of disease are a major focus of the project; they permit detailed analysis of genetic susceptibility, provide the basis for gene mapping, and provide a high risk population for analysis of other risk factors. The details of the research project for each trait vary according to our current level of understanding, but three common goals exist for all three studies consisting of: 1) definition and genetic analysis of precursor lesions of common cancers. 2) analysis of heritable and environmental factors which affect the expression of the precursor phenotype, and 3) analysis of factors which affect the conversion of the precursor lesion to malignancy. Cumulatively these studies amount to a continual refinement of the genotypic description of the susceptibility loci. We have made considerable progress defining the precursor lesions for colon cancer and melanoma, although these descriptions will be greatly furthered by project. The definition of genetic precursors for breast cancer is in the initial stage. By studying sites with a variable level of knowledge of the phenotype and role of the precursor, we can rapidly apply experience gained in one project to the others utilizing the infrastructure common to all the projects.