As one of the DNA repair genes, ataxia-telangiectasia mutated gene which is responsible for the multisystem autoxomal recessive disorder ataxia-telangiectasia, plays a crucial role in the recognition, signaling and repair of DNA damage, especially DNA double-strand breaks. The ATM protein is a member of phosphoinositide 3-kinase and can be activated by DSBs caused by ionizing radiation or reactive oxygen intermediates. Once activated, ATM can phosphorylate various downstream substates that function in cell cycle arrest, apoptosis and DNA repair, such as p53, NBS1, BRCA1 and Chk2. Therefore,EPI-001 genetic variants in ATM gene may lead to the structure and function change of the protein and act as important factors indicating individual susceptibility to cancer. ATM – 111G.A resides in the promoter of ATM gene. Increasing studies have shown that variations in the DNA promoter sequence may potentially alter the affinities of multiple regulatory proteins-DNA interactions or the specificity of the transcriptional process. Although this polymorphism makes no amino acid change, the alleles may have different binding affinity to the transcription factor and exhibit different levels of mRNA expression. Zhang et al. PCS1055 dihydrochloride declared that ATM rs189037 AA genotype was associated with a lower ATM mRNA levels than GG genotype in lung tissue samples. Their results showed that the G-to-A change might create a transcriptional inhibitor-binding site for ATM rs189037 A allele promoter and subsequently reduce the ATM mRNA expression. Consequently, lower expression of ATM might cause elevated sensitivity to ionizing radiation, defects in the activation of cell cycle checkpoints, a reduced capacity for DNA repair and abnormal apoptosis. All of these features would contribute to increased individual cancer susceptibility. In recent years, a number of studies have evaluated the association between this polymorphism and cancer risk, such as thyroid carcinoma, oral cancer, breast cancer, leukemia, nasopharyngeal carcinoma, glioma and lung caner. Previous studies of ATM rs189037 have included cigarette smokers as cases and controls that made it difficult to judge whether this polymorphism were associated with lung cancer or tobacco use.