Biological Impact of E-Cigarettes on Lung Carcinogenesis
Initial Award Abstract
There is an urgent need to quickly identify new tobacco products that pose a serious health risk to consumers. We have focused on electronic cigarettes (ECIGs) due to their rapidly growing popularity despite the absence of data on whether or not they cause cancer. The ECIG is a battery-powered electronic nicotine delivery system (ENDS) designed to deliver nicotine without combusting tobacco. Since nicotine is not generally viewed to cause cancer, ECIGs have been advertised to be a safer alternative to tobacco cigarettes (TCIGs). While the tobacco industry has intensified the development and marketing of these products, the FDA has not been able to regulate ECIGs due to the lack of information on the long-term health effects of ECIGs. Lung cancer researchers must test whether ECIGs cause cancer to inform the FDA as it makes several key decisions: Are ECIGs (1) a safe alternative to TCIGs, (2) a less harmful version of TCIGs, (3) a useful stop-smoking tool, or (4) a new product just as harmful as TCIGs that may encourage more people to start smoking.
The main goal of this research is to determine whether normal lung epithelial cells exposed to ECIGs turn into cancer cells. Our novel findings suggest that exposure to ECIGs with high nicotine content contributes to the aggressive behavior of lung epithelial cells that have mutations in P53 and KRAS, which are commonly observed in the airways of former and current smokers. Our preliminary data indicate that in one human cell line exposure to ECIGs with high nicotine content enhances the tumor-initiating capacity of P53/KRAS-mutated lung epithelial cells. This ECIG exposure also induces gene expression patterns similar to those resulting from TCIG exposure. These finding suggest exposure to ECIGs may be as harmful as TCIGs in promoting cancer in the lung epithelial cells.
The specific aims of this study are: (1) to further assess the effect of ECIG exposure on tumor formation and motility in multiple human epithelial cell lines to determine if our initial observations are consistent across subjects; (2) to identify the genetic changes caused in lung epithelial cells exposed to ECIGs; (3) to determine if the genetic changes caused by ECIG exposure are sufficient to turn normal lung epithelial cells into cancer cells. By doing this work, we expect to be the first group to determine if ECIGs have the potential to cause cancer and to identify which smokers will have negative health responses to ECIGs. Our findings have the potential to impact the number of people who develop lung cancer in the US and worldwide, therefore our studies are directly related to cancer prevention.