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标题：Biomarkers of Tobacco Smoke Exposure in Racial/Ethnic Groups at High Risk for Lung Cancer
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作者：Pebbles Fagan ; Eric T. Moolchan ; Pallav Pokhrel 等
期刊名称：American journal of public health
印刷版ISSN：0090-0036
出版年度：2015
卷号：105
期号：6
页码：1237-1245
DOI：10.2105/AJPH.2014.302492
语种：English
出版社：American Public Health Association
摘要：Objectives. We examined biomarkers of tobacco smoke exposure among Native Hawaiians, Filipinos, and Whites, groups that have different lung cancer risk. Methods. We collected survey data and height, weight, saliva, and carbon monoxide (CO) levels from a sample of daily smokers aged 18–35 (n = 179). Mean measures of nicotine, cotinine, cotinine/cigarettes per day ratio, trans 3′ hydroxycotinine, the nicotine metabolite ratio (NMR), and expired CO were compared among racial/ethnic groups. Results. The geometric means for cotinine, the cotinine/cigarettes per day ratio, and CO did not significantly differ among racial/ethnic groups in the adjusted models. After adjusting for gender, body mass index, menthol smoking, Hispanic ethnicity, and number of cigarettes smoked per day, the NMR was significantly higher among Whites than among Native Hawaiians and Filipinos (NMR = 0.33, 0.20, 0.19, P ≤ .001). The NMR increased with increasing White parental ancestry. The NMR was not significantly correlated with social–environmental stressors. Conclusions. Racial/ethnic groups with higher rates of lung cancer had slower nicotine metabolism than Whites. The complex relationship between lung cancer risk and nicotine metabolism among racial/ethnic groups needs further clarification. Cigarette smoking is the leading cause of preventable death in the United States and causes more than 90% of all lung cancers. 1 Native Hawaiians and Filipinos have higher lung cancer morbidity and mortality rates than Whites, 2 and why these disparities exist is unclear. For example, Native Hawaiians and African Americans have disproportionately higher lung cancer risk than Whites and Japanese, even among those smoking 10 cigarette per day. 3 One study showed lower quit rates and higher rates of nicotine dependence among Native Hawaiian smokers than among White adult smokers, but racial/ethnic disparities in lung cancer remain largely unexplained. 4 Nicotine is the primary addictive substance in cigarettes that maintains smoking, but the evidence is insufficient to conclude that it causes cancer in humans. 5 However, the 2014 Surgeon General’s Report concluded that the evidence is sufficient to infer that nicotine activates multiple biological pathways through which smoking increases the risk of disease. 5 An important biological pathway to examine is the elimination of nicotine from the body because its presence in the body triggers cellular pathways involved in carcinogenesis. Nicotine metabolism is primarily mediated by the enzyme cytochrome P450 2A6 (CYP2A6) in the liver. 6 CYP2A6 is responsible for 70% to 80% of nicotine metabolism. 7 Nearly 80% of nicotine is metabolized to cotinine (COT), 6,8 and 50% to 60% of COT is then metabolized to trans 3′ hydroxycotinine (3HC). 7–10 Because most of the renal clearance of nicotine is through 3HC, 7 recent studies have examined the nicotine metabolite ratio (NMR), the ratio of 3HC to COT, as a valid measure of nicotine metabolic activity. 9–11 The NMR is highly correlated with the CYP2A6 genotype 12–15 and the oral clearance of nicotine in smokers ( r = .90). 11 Studies have generally shown that among smokers, the higher the NMR ratio is, the greater the nicotine clearance. 16 Several studies have suggested that CYP2A6 may be responsible for not only the metabolic pathways of nicotine but also the bioactivation of tobacco-specific nitrosamines, 7,17 including 4-(methyl-nitrosamino)-1-(3pyridyl)-1-butanone (NNK), which has been associated with lung cancer, 18 and N ′-nitrosonornicotine (NNN). 19 Studies have suggested that people with low levels of CPY2A6 activity may be less efficient in bioactivating tobacco smoke precarcinogens to carcinogens and are at less risk for lung cancer. 20–22 However, studies have not confirmed a clear link among CYP2A6 activity, cancer, and nicotine. Previous studies have suggested that African Americans, 23–26 Asians, 23,26,27 Hispanics, 23–25 and people of mixed ethnicity have slower nicotine metabolic rates than Whites. 23 However, it is unclear why we consistently observe slower rates of nicotine metabolism 23–26 but higher rates of lung cancer 28,29 among African Americans. Previous studies have not included samples of Native Hawaiians, whose lung cancer disparities are similar to those of African Americans and Filipinos, who also have higher lung cancer morbidity and mortality rates than Whites. 2 To help clarify what is known about nicotine metabolic rates in racial/ethnic groups with higher lung cancer rates, we compared biomarkers of tobacco smoke exposure in Native Hawaiian, Filipino, and White young adult daily smokers. We hypothesized that Native Hawaiians and Filipinos would have slower nicotine metabolism than Whites.