Exposure to the carcinogen 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone (NNK) in smokers from 3 populations with different risks of lung cancer

Abstract

Native Hawaiian smokers are at higher risk and Japanese-American smokers at lower risk of lung cancer (LC), compared with white smokers, even after accounting for smoking history. Because variation in carcinogen exposure/metabolism may occur separately of smoking amount, we compared urinary biomarkers of uptake and detoxification of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-a potent lung carcinogen-among 578 smokers in these ethnic/racial groups in Hawaii. We measured the NNK metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronide (NNAL-Gluc) and examined total NNAL (NNAL 1 NNAL-Gluc) and the NNAL detoxification ratio (NNAL-Gluc:NNAL). Native Hawaiians and Japanese-Americans had lower age-and sex-adjusted mean total NNAL, compared with whites. When further adjusting for urinary nicotine equivalents (the sum of nicotine, cotinine, trans-3 0 -hydroxycotinine and their respective glucuronides), only the difference between Japanese-Americans and whites was eliminated. Therefore, consistent with their lower LC risk, a lower cigarette smoke exposure explains the lower NNK dose of Japanese-Americans, but it does not explain that of Native Hawaiians. The mean detoxification ratio was also lower in Native Hawaiians and Japanese-Americans, compared with whites, even after adjusting for nicotine equivalents (p < 0.0001). Lower NNAL glucuronidation in Native Hawaiians might contribute to their increased LC risk; however, this is inconsistent with the low glucuronidation ratio similarly observed in the low-risk Japanese-American group and because Native Hawaiians had lower total NNAL levels. Thus, exposure and detoxification of NNK are unlikely to explain, by themselves, the differences in LC risk among the 3 populations studied. ' 2009 UICC

Secondhand smoke exposure within semi-open air cafes and tobacco specific 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) concentrations among nonsmoking employees

“…One of the most extensively investigated TSNAs in tobacco products is NNK (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone), a potent carcinogen that is metabolized in the liver to form NNAL (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanonol) [2,3]. NNAL concentrations within subjects have been associated with a higher risk for developing lung cancer among smokers, indicating its use as a biomarker of lung cancer risk among smokers [4,5]. While research has extensively associated secondhand smoke (SHS) concentrations with particulate matter less than 2.5 microns (PM 2.5 ) and human biomarkers, the impact of occupational exposure to SHS in semiopen cafes and TSNA uptake remains relatively unexplored [6][7][8].…”

Racial Differences in the Relationship Between Number of Cigarettes Smoked and Nicotine and Carcinogen Exposure

“…Similarly, Derby et al (2009) found in a study of Native Hawaiian, White, and Japanese American smokers that racial differences were seen in the relationship between CPD and urine NNAL, but these racial differences were eliminated when the relationship between urine nicotine equivalents and NNAL was examined. Roethig et al (2009) reported a strong correlation between urine nicotine equivalents and urine NNAL but did not compare the relationship between CPD and urine NNAL.…”

Tobacco carcinogen NNK-induced lung cancer animal models and associated carcinogenic mechanisms

“…For example, NNK-induced miRNA changes should been studied in lung cancer models [147][148][149]. A whole genome and transcriptome analysis should be performed in NNK-induced lung cancers, which will provide information of a new paradigm of mechanism of NNK-induced carcinogenesis, and help to explain the differences of lung cancer risk among different individuals and populations [150][151][152]. In addition, these NNK-induced lung cancer animal models should be further improved because of their relatively long latency.…”