Cytokinesis-blocked micronucleus cytome assay and spectral karyotyping as methods for identifying chromosome damage in a lung cancer case-control population.

Lung cancer is the leading cause of all cancer-related deaths in the US. The need to develop more accurate cancer risk assessment tools is imperative to improve the ability to identify individuals at greatest risk of developing disease. The Cytokinesis-Blocked Micronucleus Cytome Assay (CBMNcyt) presents a sensitive and specific method of assessing DNA damage. We have previously reported that this assay is sensitive to genetic damage caused by the tobacco-specific nitrosamine 4-(methylnitrosamino)−1-(3-pyridyl)−1-butanone (NNK), and that binucleated cells with micronuclei, nucleoplasmic bridges and nuclear buds are strong predictors of lung cancer risk. The current study confirmed our previous findings and sought to identify the specific chromosomes involved in lung carcinogenesis. Spectral karyotyping was conducted on a subset of lung cancer cases [n = 116] and cancer-free controls [n = 126] with the highest CBMNcyt endpoints, on baseline and NNK-treated blood lymphocytes. After adjusting for age, gender, race/ethnicity, smoking status, and pack and smoke years, consistent significant associations between chromosome: 9, 19, 22, X, at baseline; chromosome: 3, 4, and 16 after NNK-induction; and chromosome: 1, 13, and 17 at both baseline and NNK-induction; and lung cancer risk (all P ≤ 0.05) were observed. Several of these chromosomes harbor critical genes involved in lung carcinogenesis, such as the FHIT gene, CDKN2A, PADPRP, and TP53. Our results indicate that the CBMNcyt assay when used in conjunction with other cytogenetic methodologies can increase our ability to identify specific chromosomal regions associated with DNA damage, thereby improving our understanding of the underlying mechanisms involved in individual cancer predisposition. © 2013 Wiley Periodicals, Inc.