Abstract LB-185: Cytokinesis-blocked micronuclei Assay (CBMN) as a biological cancer risk assessment tool

Abstract

Abstract Lung cancer is the leading cause of all cancer-related deaths in the US. Given the lack of effective of screening modalities, the need to develop more accurate cancer risk assessment tools is imperative to improve the ability to identify individuals that are at greatest risk of developing this disease. The Cytokinesis-Blocked Micronuclei Assay (CBMN) presents a sensitive, specific, and rapid method of assessing DNA damage, a hallmark of cancer. We have previously reported that this assay is extremely sensitive to genetic damage caused by the tobacco specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and that the binucleated cells with micronuclei, nucleoplasmic bridges, and nuclear buds in lymphocytes (chromosome damage endpoints measured by the assay) are strong predictors of lung cancer risk. To further identify the specific chromosomes involved in lung carcinogenesis, we conducted Spectral Karyotyping (SKY) on a population of n=116 cases and n=126 controls on whom CBMN data are available. SKY was performed on both baseline and NNK-treated blood lymphocytes. After adjusting for age, gender, race/ethnicity, smoking status, pack years (intensity), and smoke years (duration), we observed consistent significant results for damage on chromosomes 1, 3, 4, 9, 13, 16, 17, 19, 22, and X (all p's ≤ 0.05) and lung cancer risk. Several of these identified chromosomes are well known to harbor critical genes involved in lung carcinogenesis, such as the FHIT gene (chromosome 3), p16/CDKN2A (chromosome 9), PADPRP (chromosome 13) and TP53 (chromosome 17). Our results support the utilization of CBMN as a cancer risk assessment tool, and when used in conjunction with other cytogenetic methodologies can increase our ability to identify specific regions of DNA damage, thereby improving our understanding of the underlying mechanisms involved in individual cancer predisposition. This work was supported by the following: Kellogg Health Scholars Program (W.K. Kellogg Foundation P0117943) NIMHS P60 MD000503 CA129050 NIHS P30 ES007784 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-185. doi:1538-7445.AM2012-LB-185