Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Cancer Epidemiol Biomarkers Prev. 2013 Jan;22(1):135-45. doi: 10.1158/1055-9965.EPI-12-0435. Epub 2012 Nov 29.
Although tobacco exposure is the predominant risk factor for lung cancer, other environmental agents are established lung carcinogens. Measuring the genotoxic effect of environmental exposures remains equivocal, as increases in morbidity and mortality may be attributed to coexposures such as smoking.
We evaluated genetic instability and risk of lung cancer associated with exposure to environmental agents (e.g., exhaust) and smoking among 500 lung cancer cases and 500 controls using the cytokinesis-blocked micronucleus (CBMN) assay. Linear regression was applied to estimate the adjusted means of the CBMN endpoints (micronuclei and nucleoplasmic bridges). Logistic regression analyses were used to estimate lung cancer risk and to control for potential confounding by age, gender, and smoking.
Cases showed significantly higher levels of micronuclei and nucleoplasmic bridges as compared with controls (mean ± SEM = 3.54 ± 0.04 vs. 1.81 ± 0.04 and mean ± SEM = 4.26 ± 0.03 vs. 0.99 ± 0.03, respectively; P < 0.001) with no differences among participants with or without reported environmental exposure. No differences were observed when stratified by smoking or environmental exposure among cases or controls. A difference in lung cancer risk was observed between nonexposed male and female heavy smokers, although it was not statistically significant (I(2) = 64.9%; P value for Q statistic = 0.09).
Our study confirms that the CBMN assay is an accurate predictor of lung cancer and supports the premise that heavy smoking may have an effect on DNA repair capacity and in turn modulate the risk of lung cancer.
Identifying factors that increase lung cancer risk may lead to more effective prevention measures.
尽管烟草暴露是肺癌的主要危险因素，但其他环境因素也是已确定的肺癌致癌物。衡量环境暴露的遗传毒性效应仍然存在争议，因为发病率和死亡率的增加可能归因于吸烟等共同暴露。
我们使用细胞分裂阻断微核（CBMN）试验评估了 500 例肺癌病例和 500 例对照者暴露于环境因素（如废气）和吸烟与遗传不稳定性和肺癌风险的关系。线性回归用于估计 CBMN 终点（微核和核质桥）的调整均值。逻辑回归分析用于估计肺癌风险，并控制年龄、性别和吸烟的潜在混杂因素。
与对照组相比，病例组的微核和核质桥水平显著升高（均值±SEM=3.54±0.04 对 1.81±0.04 和均值±SEM=4.26±0.03 对 0.99±0.03；P<0.001），且在报告有或没有环境暴露的参与者之间无差异。在病例或对照者中，按吸烟或环境暴露分层时，未观察到差异。在非暴露的男性和女性重度吸烟者中观察到肺癌风险存在差异，尽管差异无统计学意义（I²=64.9%；Q 统计量的 P 值=0.09）。
我们的研究证实，CBMN 试验是肺癌的准确预测指标，并支持重度吸烟可能影响 DNA 修复能力，从而调节肺癌风险的前提。
确定增加肺癌风险的因素可能会导致更有效的预防措施。
