ATM GENE IN BREAST CANCER--PROSPECTIVE CLINICAL TRIAL

共济失调毛细血管扩张症(AT)是一种多方面的常染色体疾病 受影响的纯合子个体的癌症发病率很高， 辐射敏感度。虽然AT病是一种罕见的疾病，但AT 杂合子可能占人口的1.4%，并显示出 患乳腺癌的家族倾向。此外，流行病学 SWIFT的研究表明，超过7%的乳房患者 癌症可能是ATM的杂合子。携带杂合子的患者 ATM可能对暴露在高剂量电离辐射下更敏感， 构成了有辐射并发症风险的亚群。 位置克隆最近产生了(ATM)基因序列，即 AT患者的突变，为实验打开了一个巨大的机会 回答有关ATM在乳腺癌流行病学中的作用的问题，以及 它在诊断和治疗电离辐射中的意义 乳腺癌患者。 我们建议评估一个突变基因(ATM)在一个 200例放射治疗患者的前瞻性临床试验 乳房的癌症。我们将监测急性皮肤反应，以及 用RT-PCR、SSCP、PTT和序列分析鉴定ATM突变。我们 将把临床观察与分子发现联系起来，以提供 支持或反对以下假设的证据：(1)AT杂合子 包括对辐射更敏感的患者队列，以及(2) 乳腺癌患者AT杂合子的发生率较高。 此外，ATM突变与急性辐射呈正相关 反应将构成ATM的基础，作为一种可能的预测分析 接受诊断和治疗的乳腺癌患者 申请。

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.