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

• Published in: International journal of cancer 2009-11, Vol.125 (10), p.2418-2424
• Main Authors: Derby, Kiersten S., Cuthrell, Kristine, Caberto, Christian, Carmella, Steven, Murphy, Sharon E., Hecht, Stephen S., Le Marchand, Loïc
• Format: Article
• Language: English
• Subjects: Aged; Asian Americans; carcinogens; Carcinogens - administration & dosage; Cross-Sectional Studies; Ethnic Groups; ethnic/racial groups; European Continental Ancestry Group; Female; Follow-Up Studies; Glucuronates - urine; Hawaii; Humans; Inactivation, Metabolic; lung cancer; Lung Neoplasms - ethnology; Lung Neoplasms - urine; Male; Middle Aged; Nicotine - urine; Nitrosamines - administration & dosage; Nitrosamines - urine; Prognosis; Pyridines - urine; Risk Factors; Smoking - adverse effects; Survival Rate; tobacco
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.24585

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 + 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′‐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