EPIDEMIOLOGIC AND GENETIC STUDIES OF BREAST CANCER

乳腺癌的流行病学和遗传学研究

• 批准号: 2096860
• 负责人: THOMAS A SELLERS
• 金额: $ 74.42万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-03-13 至 1996-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2096860
• 关键词: breast neoplasm /cancer diagnosis; breast neoplasms; cancer risk; case history; death certificates; environment related neoplasm /cancer; family genetics; female; gene expression; genetic polymorphism; health surveys; human morbidity; human mortality; human subject; interview; linkage mapping; longitudinal human study; mammography; neoplasm /cancer epidemiology; neoplasm /cancer genetics; pathology; phenotype; questionnaires; statistics /biometry

The known risk factors for breast cancer - environmental, behavioral and genetic - account only for about 25% of the variability in incidence. Investigations of the interplay of genes and environment are needed to elucidate the pathogenesis of the disease. The purpose of the proposed research is to 1) determine the morbidity and mortality status of an established cohort of first- and second-degree female relatives (sisters, daughters, nieces, granddaughters) of a group of breast cancer probands originally studied at the University of Minnesota between 1944 and 1952; 2) to examine how epidemiologic risk factors influence lifetime cumulative risk by performing segregation analyses that incorporate environmental/behavioral covariates (including parenchymal pattern) using breast cancer and some or all subtypes of benign breast disease as phenotypes; 3) to explore the genetic heterogeneity of breast cancer in subsets of families defined by both the types of malignancies observed and histologic type of the proband (determined by a review of the pathology slides from the original cohort); 4) to perform genetic linkage analyses on a subset of informative families using a candidate gene approach to confirm the existence of a susceptibility gene(s). Detailed, documented histories of breast and other cancers are known for both maternal and paternal blood lines. These data are noteworthy for several reasons: 1) the sampling scheme at baseline was population-based and is easily allowed for in the analyses; 2) the number of generations with complete cancer histories minimizes the uncertainty of inherited susceptibility to diseases with variable age at onset; 3) the large number of families permits exploration of genetic heterogeneity of breast cancer and minimizes the misclassification of families as sporadic, familial or hereditary; and 4) a number of medical history/reproductive risk factors were collected on these relatives at baseline. Using established tracking procedures, we will update the vital status of family members and extend the pedigrees to include grandchildren. We have already successfully located at least one family member in all of the families selected for the pilot study. Questionnaire data, mammographies and blood samples will be obtained. Outcomes of the analysis will include a quantitative risk of breast cancer attributable to a family history; information on the pattern of inheritance of susceptibility to breast and other cancers; and evidence to support the physical location of a susceptibility gene(s). The proposed project will provide valuable information on the genetic epidemiology of breast cancer vital to primary prevention of the disease.

乳腺癌的已知危险因素 - 环境，行为和 遗传 - 仅占发病率变异性的25％。 需要对基因与环境的相互作用进行调查 阐明该疾病的发病机理。 提议的目的 研究是1）确定一个 建立的一级和二级女性亲戚（姐妹， 一组乳腺癌概率的女儿，侄女，孙女） 最初在1944年至1952年之间在明尼苏达大学学习； 2） 检查流行病学风险因素如何影响终生累积 通过进行隔离分析来冒险 使用环境/行为协变量（包括实质模式） 乳腺癌和良性乳房疾病的某些或所有亚型 表型； 3）探索乳腺癌的遗传异质性 两种观察到的恶性肿瘤类型定义的家庭子集和 概率的组织学类型（由病理学的综述确定 原始队列的幻灯片）； 4）对 使用候选基因方法确认的一部分信息家庭 易感基因的存在。 详细的，有记录的乳房和其他癌症的历史 母亲和父亲的血管。 这些数据值得注意 几个原因：1）基线的抽样方案是基于人群的 并很容易进行分析； 2）世代的数量 完整的癌症历史可以最大程度地减少遗传的不确定性 发作时年龄变化的疾病的敏感性； 3）大量 家庭允许探索乳腺癌的遗传异质性 并最大程度地减少对家庭的错误分类为零星，家族或 遗传; 4）许多病史/生殖风险因素 在基线上收集在这些亲戚上。 使用已建立的跟踪 程序，我们将更新家庭成员的生命状况并扩展 谱系包括孙子。 我们已经成功 在所有被选中的家庭中至少一个家庭成员 试点研究。 问卷数据，乳房X线和血液样本将是 获得。 分析结果将包括定量风险 乳腺癌归因于家族史；有关模式的信息 对乳房和其他癌症的易感性的遗传；和证据 支持易感基因的物理位置。 拟议的项目将提供有关遗传的有价值的信息 乳腺癌的流行病学对疾病初级预防至关重要。