Kim Jin Hee, Kim Heon, Lee Kye Young, Choe Kang-Hyeon, Ryu Jeong-Seon, Yoon Ho Il, Sung Sook Whan, Yoo Keun-Young, Hong Yun-Chul
Department of Preventive Medicine, Seoul National University College of Medicine, Republic of Korea.
Hum Mol Genet. 2006 Apr 1;15(7):1181-6. doi: 10.1093/hmg/ddl033. Epub 2006 Feb 23.
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.
共济失调毛细血管扩张症突变（ATM）基因已知可被DNA损伤激活，并参与细胞周期停滞、细胞凋亡和DNA修复。因此，ATM基因多态性可能是预测个体患肺癌易感性的重要因素。为了评估ATM基因多态性在肺癌发生中的作用，我们测定了616例肺癌患者和616例无癌对照者的ATM多态性位点-4518A>G、IVS21-77C>T、IVS61-55T>C和IVS62+60G>A的基因型。当分别评估所选ATM基因型的影响时，只有一种ATM基因型（IVS62+60G>A）与肺癌风险相关。该位点（IVS62+60G>A）携带A等位基因的受试者患肺癌的风险显著高于携带G等位基因的受试者[比值比（OR）=1.6，95%置信区间（CI）1.1-2.1]。当研究四个ATM单核苷酸多态性位点（-4518A>G、IVS21-77C>T、IVS61-55T>C和IVS62+60G>A）的单倍型时，与最常见的单倍型GCCA相比，ATTA单倍型显示患肺癌的风险显著增加（OR=7.6，95%CI 1.7-33.5）。此外，与没有（NN）TA单倍型的受试者相比，携带（NN）TA单倍型的受试者患肺癌的风险显著增加（OR=13.2，95%CI 3.1-56.1）。因此，我们的结果表明，ATM基因的多态性或单倍型在肺癌发生中起重要作用。
