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

Int J Cancer. 2009 Nov 15;125(10):2418-24. 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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

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


  • 4-((methylnitrosoamino)-1-(3-pyridyl)but-1-yl)beta-omega-glucosiduronic acid
  • Carcinogens
  • Glucuronates
  • Nitrosamines
  • Pyridines
  • Nicotine
  • 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone
  • 4-(methylnitrosamino)-1-(3-pyridyl)-1-butan-1-ol