BREAST CANCER, RADIATION EXPOSURE, AND THE ATM GENE

乳腺癌、辐射暴露和 ATM 基因

• 批准号: 2908946
• 负责人: JONINE L. BERNSTEIN
• 金额: $ 229.96万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2908946
• 关键词: blood chemistry; breast neoplasms; cancer risk; clinical research; cooperative study; female; gene environment interaction; gene expression; genetic susceptibility; human subject; neoplasm /cancer epidemiology; neoplasm /cancer genetics; questionnaires; radiation carcinogenesis; women's health

The objective of this study is to investigate gene-environment interactions in the etiology of breast cancer. We propose to establish a repository of epidemiologic risk factor information and biologic specimens from 900 women with asynchronous bilateral breast cancer and 2700 women with unilateral breast cancer who will be ascertained through 6 population-based tumor registries in the US and Denmark. All subjects will be interviewed using a structured questionnaire and blood samples will be collected for genetic analyses. Our initial plan for using this repository is to examine the interaction of radiation exposure, the ATM gene, and breast cancer. Ionizing radiation is known to be a breast carcinogen and recent studies suggest that the ATM gene may increase susceptibility to radiation-induced breast cancer. Our hypothesis is that women who are ATM gene carriers and who have received radiation therapy as part of breast conservation treatment, are at especially high risk of developing second primary contralateral breast cancer. We will also provide descriptive statistics on the prevalence of ATM in this large population-based sample of women. ATM heterozygosity will be assessed through an efficient staged approach appropriate for analysis of this complex gene. For subjects who received RT, radiation scatter dose to the contralateral breast will be reconstructed. The unique repository that we establish will be critical for future interdisciplinary investigations into the mechanisms and nature of gene-gene and gene-environment interaction influencing susceptibility to breast cancer. The study of second primaries presents a particularly promising context in which to disentangle the complex interactions among hormonal, genetic, and environmental factors influencing breast carcinogenesis as any important etiologic factors (e.g. genetic abnormalities) will be more prevalent among women who already have breast cancer than in the general population. Further, the rising incidence of breast cancer coupled with improved survival, has placed an increased number of women at risk for second primary breast cancer making it an issue of public health importance.

本研究的目的是调查乳腺癌病因中基因与环境的相互作用。 我们建议建立一个流行病学危险因素信息和生物样本库，其中包括 900 名非同步双侧乳腺癌女性和 2700 名单侧乳腺癌女性，这些女性将通过美国和丹麦的 6 个基于人群的肿瘤登记处进行确定。 所有受试者都将使用结构化问卷进行访谈，并收集血液样本进行基因分析。 我们使用该存储库的最初计划是检查辐射暴露、ATM 基因和乳腺癌之间的相互作用。 已知电离辐射是一种乳腺癌致癌物，最近的研究表明 ATM 基因可能会增加对辐射诱发乳腺癌的易感性。 我们的假设是，作为 ATM 基因携带者并接受放射治疗作为保乳治疗一部分的女性，患第二原发对侧乳腺癌的风险特别高。 我们还将提供有关 ATM 在这一庞大的女性人口样本中患病率的描述性统计数据。 ATM 杂合性将通过适合分析该复杂基因的有效分阶段方法进行评估。 对于接受 RT 的受试者，将重建对侧乳房的辐射散射剂量。我们建立的独特存储库对于未来对影响乳腺癌易感性的基因-基因和基因-环境相互作用的机制和性质的跨学科研究至关重要。 第二次初选的研究提供了一个特别有前景的背景，可以理清影响乳腺癌发生的激素、遗传和环境因素之间复杂的相互作用，因为任何重要的病因（例如遗传异常）在已经患有乳腺癌的女性中比在普通人群中更为普遍。 此外，乳腺癌发病率的上升加上生存率的提高，使越来越多的女性面临第二原发性乳腺癌的风险，使其成为一个具有重要公共卫生意义的问题。