title: Use of the cytokinesis-blocked micronucleus assay to detect gender differences and genetic instability in a lung cancer case-control study.
abstract: 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 coexposures 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 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).
  
  
  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.
  
  
  CONCLUSIONS
  Identifying factors that increase lung cancer risk may lead to more effective prevention measures.
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Michelle K
authors.initials: MK
authors.lastname: McHugh
authors.forename: Mirtha S
authors.initials: MS
authors.lastname: Lopez
authors.forename: Chung-Han
authors.initials: CH
authors.lastname: Ho
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Spitz
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Etzel
authors.forename: Randa A
authors.initials: RA
authors.lastname: El-Zein
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D016022:Case-Control Studies; D016001:Confidence Intervals; D048749:Cytokinesis / Q000235:genetics*; D004249:DNA Damage; D004781:Environmental Exposure / Q000009:adverse effects*; D005260:Female; D042822:Genomic Instability / Q000235:genetics*; D006801:Humans; D016014:Linear Models; D016015:Logistic Models; D008175:Lung Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D008297:Male; D015162:Micronucleus Tests / Q000379:methods; D008875:Middle Aged; D015999:Multivariate Analysis; D016273:Occupational Exposure / Q000009:adverse effects; D012016:Reference Values; D018570:Risk Assessment; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects*