Tobacco use is the primary risk factor for lung cancer, the leading cause of cancer deaths in the US. Quitting, however, is challenging due to the addictive nature of nicotine. Thus, preventing lung carcinogenesis in conjunction with smoking cessation may be necessary. Racial disparities also exist - African American (AA) smokers, with the same level of tobacco consumption, are at the highest risk of developing lung cancer. 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is one key carcinogen in tobacco for human lung cancer risk and its differential uptake in AA and CA smokers may contribute to the disparity. AA smokers also have the lowest success rate in quitting. Kava is a daily beverage to help people relax and improve the quality of sleep. It is commercially available in US as a dietary supplement. Epidemiological data suggest that kava consumption may reduce cancer risk. Its relaxing property may help reduce tobacco dependence/use. Our preclinical data showed that kava completely blocked NNK induced tumorigenesis in A/J mice with enhancing NNK detoxification and reducing DNA damage as the potential mechanism. Building upon these, a pilot pre- and post- one-week kava trial was performed among smokers (n = 21). The results showed that kava was well-tolerated with high compliance and there were no signs of adverse effects when rigorous safety measures were implemented. Excitingly, the results suggested that one-week kava intake helped smokers 1) reduce tobacco use; 2) reduce the amounts of urinary DNA adducts; and 3) increase urinary excretion of NNAL. Specifically, urinary Total Nicotine Equivalent (TNE), the sum of nicotine N-oxide, total nicotine, cotinine, and 3-HO-cotinine, was used to estimate tobacco use and one-week kava use led to a 29.8% reduction in TNE (p < 0.001). Urinary 3-methyladenine (3-mA), a NNK-dependent DNA adduct biomarker, was used to estimate NNK-induced DNA damage and one week kava used led to a 33.6% reduction (p = 0.014). Lastly, urinary total NNAL was used as a biomarker for NNK excretion and one-week kava use led to a 95% increase (p = 0.002). Plasma cortisol of smokers, a stress biomarker, decreased by > 40% (p<0.01) after kava use, which may contribute to the reduction in tobacco use. The 21 participants include 13 CA, 7 AA and one American Indian. The impact of kava was also analyzed between AA and CA smokers. The reductions in urinary TNE and 3-mA were more pronounced in AA smokers while the increase in urinary NNAL was higher in AA smokers as well. Consistently, the reduction in plasma cortisol was greater in AA than CA smokers. The results from this pilot trial indicate kava’s potential to reduce lung cancer risk via reducing tobacco use, enhancing NNK/NNAL detoxification, and reducing DNA damage. The results also strongly suggest kava’s unique potential to address the associated racial disparities. Future rigorous trial is needed to confirm these observations.

Note: This abstract was not presented at the meeting.

Citation Format: Chengguo Xing, Yi Wang, Naomi Fujioka, Sreekanth Narayanapillai, Junxuan Lu. Potential of kava in reducing lung cancer risk, tobacco use, and associated disparities [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3333.