ATM GENE IN BREAST CANCER--PROSPECTIVE CLINICAL TRIAL

乳腺癌中的 ATM 基因——前瞻性临床试验

• 批准号: 6300543
• 负责人: ANATOLY DRITSCHILO
• 金额: $ 19.95万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2001-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6300543
• 关键词: ataxia telangiectasia; breast neoplasm /cancer diagnosis; breast neoplasms; cancer complication; cancer risk; clinical research; clinical trials; comorbidity; gene expression; gene mutation; human subject; human therapy evaluation; ionizing radiation; neoplasm /cancer epidemiology; neoplasm /cancer genetics; neoplasm /cancer surgery; outcomes research; polymerase chain reaction; preoperative state; radiation sensitivity; single strand conformation polymorphism; statistics /biometry

Ataxia telangiectasia (AT) is a multi-faceted autosomal disease in which homozygous affected individuals have high cancer rates and extreme radiation sensitivity. Although the AT disease is a rare entity, AT heterozygotes may constitute an estimated 1.4% of the population, and show a familial disposition to breast cancer. Furthermore, epidemiological studies by Swift have suggested more than 7% of patients with breast cancer may be heterozygotes for ATM. Patients who are heterozygotes for ATM may be more sensitive to exposure to high doses of ionizing radiation, constituting a subpopulation at risk for radiation complications. Positional cloning has recently yielded the (ATM) gene sequence that is mutated in AT patients, opening a tremendous opportunity to experimentally address questions on the role of ATM in breast cancer epidemiology, and its significance to diagnostic and therapeutic ionizing radiation used in breast cancer patients. We propose to evaluate the presence of a mutated gene (ATM) in a prospective clinical trial of 200 patients undergoing radiation therapy to the breast for carcinoma. We will monitor acute skin reactions, and identify ATM mutations using RT-PCR, SSCP, PTT and sequence analysis. We will correlate clinical observations to molecular findings to provide evidence in support or against the hypotheses that (1) AT heterozygotes comprise a more "radiation sensitive" cohort of patients, and (2) that patients with breast cancer have a higher incidence of AT heterozygosity. Furthermore, a positive correlation of ATM mutations to acute radiation reactions will form the basis for ATM as a possible predictive assay for breast cancer patients undergoing diagnostic and therapeutic radiation applications.

毛细血管扩张共济失调 (AT) 是一种多方面的常染色体疾病，其中 受纯合子影响的个体癌症发病率高且极端 辐射敏感性。尽管 AT 疾病十分罕见，但 AT 杂合子估计占人口的 1.4%，并显示 乳腺癌的家族倾向。此外，流行病学 Swift 的研究表明，超过 7% 的乳腺癌患者 癌症可能是ATM的杂合子。杂合子患者 ATM 可能对暴露于高剂量电离辐射更敏感， 构成有辐射并发症风险的亚群。 最近通过定位克隆产生了 (ATM) 基因序列，即 AT 患者中发生突变，为实验提供了巨大的机会 解决有关 ATM 在乳腺癌流行病学中的作用的问题，以及 其对诊断和治疗电离辐射的重要性 乳腺癌患者。 我们建议评估突变基因（ATM）的存在 200 名接受放射治疗的患者参与的前瞻性临床试验 乳腺癌。我们将监测急性皮肤反应，并且 使用 RT-PCR、SSCP、PTT 和序列分析识别 ATM 突变。我们 将临床观察与分子发现相关联，以提供 支持或反对以下假设的证据：(1) AT 杂合子 包括更加“辐射敏感”的患者群体，并且 (2) 乳腺癌患者AT杂合性发生率较高。 此外，ATM 突变与急性辐射呈正相关 反应将构成 ATM 的基础，作为可能的预测分析 接受放射诊断和治疗的乳腺癌患者 应用程序。