Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan, R.O.C.
Int J Mol Med. 2010 Jan;25(1):165-70.
Polymorphisms in DNA repair genes may be associated with differences in repair capacity of DNA damage and may thereby influence an individual's susceptibility to lung cancer. We investigated the association between the -93G-->A polymorphism in the mismatch repair hMLH1 gene for its role in the susceptibility and survival of non-small cell lung cancer (NSCLC) patients. Using a case-control study design, 165 NSCLC patients and 193 controls with similar range for age, gender and smoking habit distributions were subjected to genotype analysis. The risk of lung cancer was estimated by logistic regression analysis. The Kaplan-Meier method was used to estimate the probability of survival and the log-rank test was used to assess the significance of the difference between survival probabilities. The homozygous variant A/A genotype was associated with a significantly increased risk for lung cancer compared with the other genotypes (Crude analysis P=0.003, Adjusted analysis P=0.011, using the logistic regression model). The patients with a homozygous variant A/A genotype had a trend toward poorer prognoses compared with other patients, especially smoking (P=0.05, by log-rank test), male (P=0.06), or squamous carcinoma (P=0.08) patients. This is the first case-control study to show a significant association between the hMLH1-93G-->A polymorphism and the susceptibility to and prognosis of lung cancer. The results herein may be useful for risk assessment and disease monitoring of NSCLC.
DNA 修复基因的多态性可能与 DNA 损伤修复能力的差异有关，并可能影响个体对肺癌的易感性。我们研究了错配修复 hMLH1 基因中的-93G-->A 多态性与非小细胞肺癌（NSCLC）患者易感性和生存的关系。采用病例对照研究设计，对 165 例 NSCLC 患者和 193 例年龄、性别和吸烟习惯分布相似的对照进行基因型分析。使用逻辑回归分析估计肺癌的风险。Kaplan-Meier 法估计生存概率，对数秩检验评估生存概率差异的显著性。与其他基因型相比，杂合子变异 A/A 基因型与肺癌的风险显著增加（粗分析 P=0.003，调整分析 P=0.011，使用逻辑回归模型）。与其他患者相比，具有纯合子变异 A/A 基因型的患者预后较差，尤其是吸烟（P=0.05，对数秩检验）、男性（P=0.06）或鳞状细胞癌（P=0.08）患者。这是第一项表明 hMLH1-93G-->A 多态性与肺癌易感性和预后之间存在显著关联的病例对照研究。本研究结果可能有助于 NSCLC 的风险评估和疾病监测。
