Abstract 1878: Evidence for the indirect relationship between self-reported exposure to environmental agents and smoking in the assessment of lung cancer risk
Authors: McHugh Michelle K. , Ho Chung-Han , Lopez Mirtha S. , Spitz Margaret R. , Etzel Carol J. , El-Zein Randa A. 
Published: August 2014

Genetic factors play a role in determining individual susceptibility to cancer. Accumulation of multiple genetic alterations leads to cancer development and is cytogenetically detectable. Our group has applied the Cytonkinesis-Blocked Micronucleus assay (CBMN) as a sensitive predictor of individual susceptibility to lung cancer (LC). The objective of this study was to investigate whether self-reported exposure to ≥1 environmental agents (asbestos, fibers, paints, dust, exhaust, bleach, solvents) is associated with increased genetic instability and/or elevated risk of LC.

We recruited 490 LC cases from an ongoing study at the University of Texas MD Anderson Cancer Center. Controls (n=500) were recruited from a large multispecialty physician group practice and frequency matched to cases by age (±5 years) and sex. Peripheral blood lymphocytes were collected and cytogenetic cultures prepared. One thousand binucleated cells per participant were scored and the frequencies of micronucleus (BN-MN), nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) were recorded. Linear regression analyses were applied to estimate the adjusted means of the CBMN. Odds ratios and 95% confidence intervals were calculated using logistic regression and to control for confounding.

We did not detect elevated odds of LC when exposure was assessed by self-report to ≥1 of the seven environmental agents. When stratified by smoking status, we found heavy smokers with ≥1 exposure had a 58% increased risk of LC compared to never smokers without exposure; yet heavy smokers with no exposure had a 79% increased risk compared to the referent group. Even though LC cases showed significantly higher frequencies than controls for all three CBMN endpoints, there were no significant differences in cases with or without exposure (p=0.15). However in controls, the differences were indirectly related to exposure. Mean BN-MN for controls without exposure (mean +SE = 2.68±0.07) was higher than the mean BN-MN for controls with ≥1 exposure (mean +SE = 2.44±0.07). We also found an indirect relationship between mean BN-MN levels and smoking among controls: never smokers (mean +SE = 2.81±0.09), light (mean +SE=2.76±0.11, moderate (mean +SE=2.51±0.11) and heavy smokers (mean +SE=2.26±0.10; p for trend=&lt;0.0001).

These results confirm our previous studies that found the CBMN assay to be a valuable tool for predicting LC risk; however, the risk confirmed by this biomarker is not related to exposure to the seven agents under study. Our new findings that CBMN frequencies were higher in the controls that were never or light smokers support the hypothesis that heavy smokers may develop a more robust DNA repair machinery due to the constant exposure to smoking-related carcinogens. These findings warrant the need for further studies to identify the underlying mechanisms involved in genetic susceptibility to lung cancer.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1878. doi:10.1158/1538-7445.AM2011-1878