Shen Hongbing, Spitz Margaret R, Qiao Yawei, Guo Zhaozheng, Wang Li-E, Bosken Carol H, Amos Christopher I, Wei Qingyi
Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Int J Cancer. 2003 Oct 20;107(1):84-8. doi: 10.1002/ijc.11346.
Tobacco-related carcinogens cause a variety of DNA damage that is repaired by different enzymatic pathways, suggesting that DNA repair plays an important role in tobacco-induced carcinogenesis. In a large hospital-based case-control study, we investigated DNA repair capacity (DRC) as a biomarker for susceptibility to nonsmall cell lung cancer (NSCLC) and evaluated the possible interaction between DRC and tobacco smoke in 467 newly diagnosed NSCLC patients and 488 cancer-free controls. We measured DRC in cultured peripheral lymphocytes using the host-cell reactivation assay with a reporter gene damaged by an activated tobacco carcinogen, benzo[a]pyrene diol epoxide. The results showed that current smokers exhibited the highest DRCs as compared to former and nonsmokers both among patients and control subjects. There were no differences of DRC among 3 different histopathologic types of NSCLC. Logistic regression analysis revealed that suboptimal DRC and pack-years smoked were independent predictors of NSCLC risk. The overall 15.5% reduction in DRC observed in the cases (7.84%) compared to the controls (9.28%) (p<0.001) was associated with an approximately 2-fold increased risk of NSCLC (adjusted odds ratio (OR) = 1.85, 95% confidence interval (CI) 1.42-2.42). There was a significant dose-response association between decreased DRC and increased risk of lung cancer. Furthermore, we observed a nonstatistically significant additive but not multiplicative interaction between DRC and pack-years smoked on lung cancer risk, particularly in the histopathologic types of NSCLC other than adenocarcinoma. The results suggest that suboptimal DRC is associated with increased risk of NSCLC and DRC may modulate the risk of lung cancer associated with smoking but the latter needs to be verified in larger studies.
烟草相关致癌物会导致多种DNA损伤，这些损伤通过不同的酶促途径进行修复，这表明DNA修复在烟草诱导的致癌过程中起着重要作用。在一项基于大型医院的病例对照研究中，我们调查了DNA修复能力（DRC）作为非小细胞肺癌（NSCLC）易感性的生物标志物，并评估了467例新诊断的NSCLC患者和488例无癌对照中DRC与烟草烟雾之间可能存在的相互作用。我们使用宿主细胞再激活试验，通过一个被活化的烟草致癌物苯并[a]芘二醇环氧化物损伤的报告基因，来测量培养的外周血淋巴细胞中的DRC。结果显示，无论是在患者还是对照受试者中，与既往吸烟者和不吸烟者相比，目前吸烟者的DRC最高。在NSCLC的3种不同组织病理学类型之间，DRC没有差异。逻辑回归分析显示，DRC欠佳和吸烟包年数是NSCLC风险的独立预测因素。与对照组（9.28%）相比，病例组（7.84%）中观察到的DRC总体降低15.5%（p<0.001）与NSCLC风险增加约2倍相关（调整后的优势比（OR）=1.85，95%置信区间（CI）1.42 - 2.42）。DRC降低与肺癌风险增加之间存在显著的剂量反应关系。此外，我们观察到DRC与吸烟包年数在肺癌风险上存在非统计学显著的相加但非相乘相互作用，特别是在腺癌以外的NSCLC组织病理学类型中。结果表明，DRC欠佳与NSCLC风险增加相关，DRC可能调节与吸烟相关的肺癌风险，但后者需要在更大规模的研究中得到验证。
