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，其中 纯合子受影响的个体具有高的癌症发病率和极端的 辐射敏感性虽然AT疾病是一种罕见的实体， 杂合子可能构成估计的1.4%的人口，并显示 乳腺癌的家族遗传倾向此外，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， 构成了有辐射并发症风险的亚群。 定位克隆最近已经产生了（ATM）基因序列， 在AT患者中发生突变，为实验性地 解决ATM在乳腺癌流行病学中的作用问题， 它对诊断和治疗电离辐射的意义， 乳腺癌患者。 我们建议评估一个突变基因（ATM）的存在， 200例接受放射治疗的患者的前瞻性临床试验， 乳腺癌我们将监测急性皮肤反应， 采用RT-PCR、SSCP、PTT和序列分析鉴定ATM突变。我们 将临床观察结果与分子发现相关联， 支持或反对以下假设的证据：（1）AT杂合子 包括更“辐射敏感”的患者群，以及（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， 反应将形成ATM作为可能的预测分析的基础， 接受诊断和治疗放射的乳腺癌患者 应用.

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.