GENETIC EPIDEMIOLOGY OF CANCER AND PREDISPOSING LESIONS

过去二十年来分子生物学的科学革命， 计算机科学已经为我们创造了基础， 了解癌症的病因。 在这个项目中，我们利用 从这些领域衍生的方法来研究三种常见的病因学 癌症及其前驱病变：1）腺瘤性息肉和结肠 癌症，2）发育不良痣和黑色素瘤，以及3）增生性乳腺疾病 和乳腺癌。 该项目的基本主题是， 分析常见癌症的前驱病变是一个主要的关键， 了解其病因。 家族聚集性疾病是一种主要的 项目的重点;他们允许详细分析基因 易感性，提供基因定位的基础，并提供高风险 分析其他危险因素。 研究的细节 根据我们目前的理解水平， 但所有三项研究都有三个共同的目标，包括： 常见癌前病变的定义和遗传学分析。（二） 影响表达的遗传和环境因素分析 的前体表型，和3）影响因素的分析， 前驱病变转化为恶性肿瘤。 累积这些 研究相当于对基因型描述的不断完善 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体病变，尽管这些描述 将通过项目得到极大的推进。 遗传前体的定义 乳腺癌的早期阶段。 通过研究网站， 不同水平的知识的表型和作用的前体，我们 可以迅速将在一个项目中获得的经验应用于其他项目， 所有项目的基础设施。

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.