Existing data show that lung cancer disparities are not explained by cigarette smoking dose and duration alone. Data from the Multiethnic Cohort Study show that Native Hawaiians and African Americans who smoked 10 cigarettes per day have an elevated risk of lung cancer compared to Japanese American, White, and Latino smokers. Prior studies also suggest that African Americans have slower nicotine metabolism compared to Whites. It remains unclear why we consistently observe slower rates of nicotine metabolism among African Americans, but higher rates of lung cancer since studies suggest that smokers with low levels of CPY2A6 activity may be less efficient in bioactivating tobacco smoke pre-carcinogens to carcinogens. Little is known about nicotine metabolism among Native Hawaiians and Filipinos who have disproportionate and unexplained lung cancer rates like African Americans.

This study compares biomarkers of tobacco smoke exposure in Native Hawaiian, Filipino, and White young adult daily smokers. We hypothesized that Native Hawaiians and Filipinos, like African Americans, would have slower nicotine metabolism compared to Whites. We collected data on sociodemographics, smoking history, and psychosocial risk factors among young adult daily smokers aged 18-35. We measured height, weight, and carbon monoxide levels among all smokers. A saliva sample was collected from each smoker using standard passive drool procedures. The geometric means were calculated for nicotine, cotinine, trans 3' hydroxycotinine, the nicotine metabolite ratio, and expired carbon monoxide and the data were compared among racial/ethnic groups. Two analysis of covariance models tested biomarker differences among racial/ethnic groups. Model 1, the unadjusted model, contained no covariates. Model 2 included gender, body mass index (BMI), menthol smoking status, Hispanic ethnicity, and the number of cigarettes smoked per day as covariates.

The sample included 44% Native Hawaiians, 16% Filipinos, and 40% Whites (n=186). Twenty-four percent of young adults were of Hispanic origin, 48% were females, and smokers had a mean BMI of 28. Forty-one percent of Filipino smokers reported Hispanic ethnicity compared to 27% of Native Hawaiian and 15% of White smokers (p< 0.02). Native Hawaiians had a higher BMI than Filipinos and Whites (31.9, 24.5, 24.8, p<0.001). Eighty-seven percent of Native Hawaiians, 72% of Filipinos, and 48% of White young adults reported menthol cigarette use. There were no differences in smoking duration or smoking consumption among racial/ethnic groups. Smokers had smoked daily for 1.5 years and smoked a mean of 14.4 cigarettes per day.

In the unadjusted and adjusted models, cotinine levels were higher among Native Hawaiians compared to Whites, but these differences were not significant among racial/ethnic groups. In the unadjusted model, the nicotine metabolic ratio was significantly lower in Native Hawaiian and Filipino smokers compared to White smokers (NMR: 0.17, 0.15, 0.27, p<0.001). In the adjusted model, the nicotine metabolite ratio remained significantly lower in Native Hawaiian and Filipino smokers compared to White smokers (NMR: 0.20, 0.19, 0.33, p<0.001).

In summary, our data show that Native Hawaiian and Filipino daily smokers have slower nicotine metabolism than White daily smokers as indicated by the nicotine metabolite ratio. Studies show that the nicotine metabolite ratio is a reliable phenotypic marker for CYP2A6 activity. However, is it not clear whether the algorithm suggesting that slow nicotine metabolizers have reduced lung cancer risk applies to all racial/ethnic groups. Resolving the complex problem of lung cancer disparities requires further investigation of multiple biological pathways to determine which lung cancer risk algorithms apply to specific racial/ethnic groups. Such investigations will allow to us to improve community, clinical, and policy-based interventions to reduce disparities.

Citation Format: Pebbles Fagan, Eric T. Moolchan, Pallav Pokhrel, Thaddeus Herzog, Kevin Cassel, Ian Pagano, Adrian Franke, Joseph Keawe'aimoku Kaholokula, Angela Sy, Linda A. Alexander, Dennis R. Trinidad, Kari-Lyn Sakuma, Carl Anderson Johnson, Alyssa M. Antonio, Dorothy Jorgensen, Tania Lynch, Crissy Kawamoto, Mark S. Clanton. Resolving the complex problem of tobacco-caused lung cancer disparities in the U.S. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr IA47.