Use of the Cytokinesis-Blocked Micronucleus Assay (CBMN) to Detect Gender Differences and Genetic Instability in a Lung Cancer Case-Control Study
Mené sur 500 patients atteints d'un cancer du poumon et sur 500 témoins, cet essai analyse la performance d'un test des micronoyaux avec blocage de la cytokinèse pour évaluer l'instabilité génétique et le risque de cancer du poumon associés au tabagisme ou à une exposition à des agents environnementaux
Background: 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 co-exposures such as smoking. Methods: 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. Results: Cases showed significantly higher levels of micronuclei and nucleoplasmic bridges as compared to 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 non-exposed male and female heavy smokers, although it was not statistically significant (I2=64.9%; P-value for Q statistic=0.09). Conclusions: 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. Impact: Identifying factors that increase lung cancer risk may lead to more effective prevention measures.
Cancer Epidemiology Biomarkers & Prevention , résumé, 2012