DNA repair and cell cycle control genes and the risk of young-onset lung cancer
DNA repair and cell cycle control genes and the risk of young-onset lung cancer
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DOI：
10.1158/0008-5472.can-06-1039
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发表时间：
2006-11-15
期刊：
影响因子：
11.2
通讯作者：
Brennan, Paul
中科院分区：
文献类型：
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作者：
Landi, Stefano;Gemignani, Federica;Brennan, Paul
接触烟草烟雾和诱变性异生物质可能会导致肺细胞中各种类型的 DNA 损伤，如果不通过 DNA 修复系统进行纠正，可能会导致细胞周期失调，并最终导致癌症。因此，遗传变异可能是决定烟草诱发肺癌易感性的一个重要因素，与一般人群相比，遗传易感性在年轻发病病例中发挥着更大的作用。因此，我们研究了来自中欧和东欧六个国家的 299 例 50 岁之前诊断的肺癌病例和 317 例对照中 34 个关键 DNA 修复和细胞周期控制基因的 102 个单核苷酸多态性 (SNP)。我们发现肺癌风险与细胞周期控制、单链/双链断裂修复或碱基切除修复相关基因的多态性没有关联。与 DNA 损伤感知 (ATM) 相关的基因的多态性以及编码参与错配修复的蛋白质（LIG1、LIG3、MLH1 和 MSH6）的四个基因的多态性发现了显着关联（P < 0.05）。与 LIG1 -7C > T 的杂合子携带者观察到最强的关联[比值比 (OR)，1.73； 95% 置信区间 (95% CI), 1.13-2.64] 和 LIG3 rs1052536 纯合子携带者 (OR, 2.05; 95% CI, 1.25-3.38)。考虑到评估的标记物数量相对较多，削弱了这些发现的重要性；因此，这些 SNP 应被视为有希望在其他独立人群中进行进一步研究的候选者。
Exposure to tobacco smoke and to mutagenic xenobiotics can cause various types of DNA damage in lung cells, which, if not corrected by DNA repair systems, may lead to deregulation of the cell cycle and, ultimately, to cancer. Genetic variation could thus be an important factor in determining susceptibility to tobacco-induced lung cancer with genetic susceptibility playing a larger role in young-onset cases compared with that in the general population. We have therefore studied 102 single-nucleotide polymorphisms (SNP) in 34 key DNA repair and cell cycle control genes in 299 lung cancer cases diagnosed before the age of 50 years and 317 controls from six countries of Central and Eastern Europe. We have found no association of lung cancer risk with polymorphisms in genes related to cell cycle control, single-strand/double-strand break repair, or base excision repair. Significant associations (P < 0.05) were found with polymorphisms in genes involved in DNA damage sensing (ATM) and, interestingly, in four genes encoding proteins involved in mismatch repair (LIG1, LIG3, MLH1, and MSH6). The strongest associations were observed with heterozygote carriers of LIG1 -7C > T [odds ratio (OR), 1.73; 95% confidence interval (95% CI), 1.13-2.64] and homozygote carriers of LIG3 rs1052536 (OR, 2.05; 95% CI, 1.25-3.38). Consideration of the relatively large number of markers assessed diminishes the significance of these findings; thus, these SNPs should be considered promising candidates for further investigation in other independent populations.