Ye Chuanzhong, Cai Qiuyin, Dai Qi, Shu Xiao-ou, Shin Aesun, Gao Yu-Tang, Zheng Wei
Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt Ingram-Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2587, USA.
Cancer. 2007 May 1;109(9):1729-35. doi: 10.1002/cncr.22592.
The ataxia-telangiectasia mutated (ATM) gene plays a critical role in cell-cycle arrest, apoptosis, and DNA repair. However, to date, no study has directly investigated the association between ATM gene expression and breast cancer survival.
ATM gene expression levels were evaluated in tumor and adjacent normal tissue from patients diagnosed with primary breast cancer or BBD using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) assays. Cox regression models were used to evaluate the association of ATM gene expression and survival in a cohort of 471 breast cancer patients.
In breast cancer cases, ATM expression in cancer tissues was decreased by approximately 50% compared with adjacent normal tissues from the same patients. In BBD cases, the expression level of the ATM gene was similar in benign tumor tissue and adjacent normal tissues. No apparent difference was found in ATM gene expression levels in adjacent normal tissues obtained from cancer patients or BBD controls. Compared with patients with the lowest tertile of the ATM mRNA, patients in the upper 2 tertiles had more favorable disease-free survival (hazard ratio [HR]=0.46, 95% confidence interval [CI]: 0.30-0.73 and HR=0.52, 95% CI: 0.33-0.81, respectively) and overall survival (HR=0.56, 95% CI: 0.35-0.92 and HR=0.70, 95% CI: 0.43-1.13, respectively).
The ATM gene expression was down-regulated in breast cancer tissues and a high ATM gene expression level in breast cancer tissue was associated with a favorable prognosis.
共济失调毛细血管扩张症突变（ATM）基因在细胞周期停滞、细胞凋亡和DNA修复中起关键作用。然而，迄今为止，尚无研究直接调查ATM基因表达与乳腺癌生存率之间的关联。
使用定量实时逆转录聚合酶链反应（RT-PCR）检测法，评估原发性乳腺癌或乳腺良性疾病（BBD）患者肿瘤组织及相邻正常组织中的ATM基因表达水平。采用Cox回归模型评估471例乳腺癌患者队列中ATM基因表达与生存率的关联。
在乳腺癌病例中，与同一患者的相邻正常组织相比，癌组织中的ATM表达降低了约50%。在BBD病例中，ATM基因在良性肿瘤组织和相邻正常组织中的表达水平相似。从癌症患者或BBD对照获得的相邻正常组织中，ATM基因表达水平未发现明显差异。与ATM mRNA处于最低三分位数的患者相比，处于最高两个三分位数的患者无病生存率更优（风险比[HR]=0.46，95%置信区间[CI]：0.30 - 0.73；HR=0.52，95% CI：0.33 - 0.81），总生存率也更优（HR=0.56，95% CI：0.35 - 0.92；HR=0.70，95% CI：0.43 - 1.13）。
乳腺癌组织中ATM基因表达下调，乳腺癌组织中高ATM基因表达水平与良好预后相关。
