Genetic polymorphisms of ataxia telangiectasia mutated affect lung cancer risk

The ataxia telangiectasia mutated (ATM) gene is known to be activated by DNA damage and involved in cell cycle arrest, apoptosis and DNA repair. Therefore, ATM gene polymorphisms may act as important factors predicting individual susceptibility to lung cancer. To evaluate the role of ATM gene polymorphisms in lung cancer development, genotypes of the ATM polymorphisms, -4518A > G, IVS21-77C > T, IVS61-55T > C, and IVS62+60G > A, were determined in 616 lung cancer patients and 616 cancer-free controls. When the effects of selected ATM genotypes were evaluated separately, only one ATM genotype (IVS62+60G > A) showed an association with lung cancer risk. Subjects with the A allele at the site (IVS62+60G > A) have significantly higher risk of lung cancer than those with the G allele [odds ratio (OR)=1.6, 95% confidence interval (CI) 1.1-2.1]. When the haplotypes of four ATM single nucleotide polymorphism sites (-4518A > G, IVS21-77C > T, IVS61-55T > C and IVS62+60G > A) were studied, the ATTA haplotype showed significantly increased risk of lung cancer compared with the GCCA haplotype, the most common haplotype (OR=7.6, 95% CI 1.7-33.5). Furthermore, subjects with the (NN)TA haplotype showed highly significant and increased risk of lung cancer when compared with those without the (NN)TA haplotype (OR=13.2, 95% CI 3.1-56.1). Therefore, our results suggest that polymorphisms or haplotypes of the ATM gene play an important role in the development of lung cancer.