Variation in Levels of the Lung Carcinogen NNAL and its Glucuronides in the Urine of Cigarette Smokers from Five Ethnic Groups with Differing Risks for Lung Cancer
Menée aux Etats-Unis à partir des données d"une cohorte multiethnique incluant 2 252 participants fumeurs, cette étude analyse les disparités ethniques dans l'association entre les niveaux de 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) et ses glucuronides mesurés dans les urines et le risque de cancer du poumon
Background: Results of the Multiethnic Cohort study (MEC) demonstrated that, for the same quantity of cigarettes smoked, African Americans (AfrAm) and Native Hawaiians (NH) have a higher risk of lung cancer compared to Whites, whereas Latinos (LA) and Japanese Americans (JA) have a lower risk. We hypothesize that the uptake and/or metabolism of the lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) could explain the differences in lung cancer risk. Methods: We measured urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronides and their sum (total NNAL), biomarkers of NNK uptake, in 2,252 smokers from the MEC. Ethnic-specific geometric means were compared adjusting for age at urine collection, sex, creatinine and total nicotine equivalents, a marker of total nicotine uptake. Results: AfrAm had the highest median total NNAL levels (1.80 pmol/ml urine) and JA the lowest (0.914 pmol/ml urine), with intermediate values in the other three groups. Geometric mean of total NNAL in AfrAm was also highest and in JA was lowest; JA geometric mean was statistically different from Whites (P=0.004). Conclusions: AfrAm had higher levels of total NNAL per ml urine than Whites while JA had lower levels, consistent with lung cancer risk among smokers in these groups. However, our data were not consistent with the high and low lung cancer risks of NH and LA smokers, respectively. Impact: The higher lung cancer susceptibility of AfrAm smokers and the lower susceptibility of JA smokers compared to Whites can be explained in part by exposure to the potent lung carcinogen NNK.