Exposure to the carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in smokers from 3 populations with different risks of lung cancer.
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.
Derby
Kiersten S
KS
Epidemiology Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu, HI 96813, USA.
Cuthrell
Kristine
K
Caberto
Christian
C
Carmella
Steven
S
Murphy
Sharon E
SE
Hecht
Stephen S
SS
Le Marchand
Loïc
L
D000368:Aged; D001213:Asian; D002273:Carcinogens / Q000008:administration & dosage*; D003430:Cross-Sectional Studies; D005006:Ethnicity; D005260:Female; D005500:Follow-Up Studies; D005965:Glucuronates / Q000652:urine*; D006254:Hawaii; D006801:Humans; D008658:Inactivation, Metabolic; D008175:Lung Neoplasms / Q000208:ethnology* / Q000652:urine*; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000652:urine; D009602:Nitrosamines / Q000008:administration & dosage* / Q000652:urine*; D011379:Prognosis; D011725:Pyridines / Q000652:urine*; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D015996:Survival Rate; D044465:White People
C099564:4-((methylnitrosoamino)-1-(3-pyridyl)but-1-yl)beta-omega-glucosiduronic acid; D002273:Carcinogens; D005965:Glucuronates; D009602:Nitrosamines; D011725:Pyridines; D009538:Nicotine; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; C099565:4-(methylnitrosamino)-1-(3-pyridyl)-1-butan-1-ol