Institute of Population Health Sciences, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County 350, Taiwan.
Lung Cancer. 2010 Aug;69(2):148-54. doi: 10.1016/j.lungcan.2009.11.007. Epub 2009 Dec 11.
The ataxia-telangiectasia mutated (ATM) gene, an important caretaker of overall genome stability, is thought to play a role in the development of human malignancy. Therefore, we hypothesized that sequence variants in ATM may influence the disposition to lung cancer. In this hospital-based matched case-control study, nine ATM single nucleotide polymorphisms (rs189037, rs228597, rs228592, rs664677, rs609261, rs599558, rs609429, rs227062, and rs664982) were genotyped in 730 lung cancer patients and 730 healthy controls. Pairwise linkage disequilibrium among nine polymorphisms in the ATM gene was very high. None of the main effects of any of the ATM polymorphisms were related to the risk of lung cancer. Interestingly, ATM polymorphisms were significantly associated with lung cancer among never smokers, and the association was modulated by low-level exposure to carcinogens such as environmental tobacco smoke. When the haplotypes of nine ATM polymorphism sites were studied, no overall association between ATM haplotypes and risk of lung cancer was found. However, the frequency distribution of haplotypes between lung cancer cases and controls was significant in the never smokers (P=0.009), demonstrating that haplotypes have a significant effect on the risk of lung cancer. In conclusion, we found that never smokers with sequence variants of the ATM gene may be at increased risk for lung cancer. Our data also suggest this association may be further modified by exposure to environmental tobacco smoke. This study suggests support to the literature that ATM polymorphisms and environmental tobacco smoke exposure have a role in lung carcinogenesis among never smokers.
共济失调毛细血管扩张突变基因（ATM）是一种重要的基因组稳定性“守护者”，被认为在人类恶性肿瘤的发生发展中发挥作用。因此，我们假设 ATM 中的序列变异可能会影响肺癌的易感性。在这项基于医院的匹配病例对照研究中，对 730 名肺癌患者和 730 名健康对照者的 ATM 单核苷酸多态性（rs189037、rs228597、rs228592、rs664677、rs609261、rs599558、rs609429、rs227062 和 rs664982）进行了基因分型。ATM 基因中九个多态性之间的连锁不平衡非常高。任何 ATM 多态性的主要作用都与肺癌的风险无关。有趣的是，ATM 多态性与从不吸烟者的肺癌显著相关，并且这种相关性受到环境烟草烟雾等致癌物质低水平暴露的调节。当研究九个 ATM 多态性位点的单倍型时，没有发现 ATM 单倍型与肺癌风险之间存在总体关联。然而，在从不吸烟者中，肺癌病例和对照组之间的单倍型频率分布存在显著差异（P=0.009），表明单倍型对肺癌的风险有显著影响。总之，我们发现 ATM 基因序列变异的从不吸烟者可能患肺癌的风险增加。我们的数据还表明，这种关联可能进一步受到环境烟草烟雾暴露的影响。这项研究支持了文献中关于 ATM 多态性和环境烟草烟雾暴露在从不吸烟者肺癌发生中的作用的观点。
