Research article summary (published 13 Nov 2009):

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

Full 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 + 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.

Author information

Author/s: Derby, Kiersten S (KS); Cuthrell, Kristine (K); Caberto, Christian (C); Carmella, Steven (S); Murphy, Sharon E (SE); Hecht, Stephen S (SS); Le Marchand, Loïc (L);

Affiliation: Epidemiology Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu, HI 96813, USA.

Grants: R01 CA 85997 (Agency:NCI NIH HHS)

Journal and publication information

Publication Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural

Journal: International journal of cancer. Journal international du cancer (Int J Cancer), published in United States. (Language: eng)

Reference: 2009-Nov; vol 125 (issue 10) : pp 2418-24

Dates: Created 2009/09/28; Completed 2009/11/05;

PMID: 19598261, status: MEDLINE (last retrieval date: 11/5/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Aged Asian Americans Carcinogens - administration & dosage Cross-Sectional Studies Ethnic Groups European Continental Ancestry Group Female Follow-Up Studies Glucuronates - urine Hawaii Humans

Lung Neoplasms - ethnology; urine Male Metabolic Detoxication, Drug Middle Aged Nicotine - urine Nitrosamines - administration & dosage; urine Prognosis Pyridines - urine Risk Factors Smoking - adverse effects Survival Rate

Associated Chemicals: 4-((methylnitrosoamino)-1-(3-pyridyl)but-1-yl)beta-omega-glucosiduronic acid (0) ; 4-(methylnitrosamino)-1-(3-pyridyl)-1-butan-1-ol (0) ; Carcinogens (0) ; Glucuronates (0) ; Nitrosamines (0) ; Pyridines (0) ; Nicotine (54-11-5) ; 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (64091-91-4)

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