Abstract 1015: Potential of kava in reducing lung cancer risk and associated disparities: Mechanism-based biomarker discovery and analysis
Authors: Xing Chengguo , Freeman Breanne , Mamallapalli Jessica , Lynch Allison , Fujioka Naomi , Salloum Ramzi G. , Malaty John , Orlando Frank , Huo Zhiguang 
Published: March 2024

Background: Lung cancer is the leading cause of cancer-related deaths. Tobacco smoke is well-recognized as the dominant risk factor. Stress, lung inflammation, air pollution and other factors also contribute to the risk of developing lung cancer Racial/ethnic disparities in lung cancer risks exit as well. The quantitative contributions of different these risk factors to lung cancer and associated disparities, however, have not been systematically characterized. One major barrier is the lack of tools to non-invasively and objectively quantify these risk factors, which precludes the identification of high-risk individuals and the development of effective prevention. Data from our group, particularly results from a pilot clinical trial, suggest that kava, traditionally consumed in the South Pacific Islands as a beverage to reduce stress and promote relaxation, may holistically reduce lung cancer risk by impacting multiple factors that contribute to lung cancer risk.

Aim: This study aims to discover mechanism-based non-invasive biomarkers reflective of different lung cancer risk factors and explore their potential roles in lung cancer risk disparities. Such biomarkers are also employed to characterize the holistic effects of kava in reducing lung cancer risk and its potential in mitigating associated disparities.

Results and Analysis: One-week of kava significantly reduced the level of nicotine exposure among smokers, quantified by the Total Nicotine Equivalents (TNE) in the 24-h urine sample. Excitingly the reduction in TNE appeared to be higher among African American smokers in comparison to participants of other race/ethnicity. Biomarkers for stress (plasma cortisol and urinary total cortisol equivalents (TCE)) were significantly reduced upon one-week kava use, which may mechanistically contribute to the reductions in tobacco use. The reduction in plasma cortisol and TCE were higher among African American smokers as well. One-week kava exposure also increased urinary excretion of total NNAL and reduced urinary 3-methyladenine (3-mA) in participants, suggestive of its ability to reduce the carcinogenicity of nicotine-derived nitrosamine ketone (NNK). Kava effects on NNAL and 3mA were again more pronounced among African American smokers.

Conclusion and future directions: These results demonstrate the potential of mechanism-based biomarkers in investigating lung cancer risks and associated disparities. Such biomarkers may also facilitate the translational development of effective and targeted interventions, such as kava, which may not only reduce lung cancer risk but also mitigate the associated disparities. Additional mechanism-based biomarkers on other tobacco carcinogens and inflammation are currently under development. Two clinical trials are ongoing that the current clinical samples will help validate these discoveries.

Citation Format: Chengguo Xing, Breanne Freeman, Jessica Mamallapalli, Allison Lynch, Naomi Fujioka, Ramzi G. Salloum, John Malaty, Frank Orlando, Zhiguang Huo. Potential of kava in reducing lung cancer risk and associated disparities: Mechanism-based biomarker discovery and analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1015.