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

Background: Results of the Multiethnic Cohort (MEC) study demonstrated that, for the same quantity of cigarettes smoked, African Americans and Native Hawaiians have a higher risk of lung cancer compared with whites, whereas Latinos and Japanese Americans 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: African Americans had the highest median total NNAL levels (1.80 pmol/mL urine) and Japanese Americans had the lowest (0.914 pmol/mL urine), with intermediate values in the other three groups. Geometric mean of total NNAL in African Americans was also highest, and in Japanese Americans it was lowest; Japanese American geometric mean was statistically different from whites (P = 0.004). Conclusions: African Americans had higher levels of total NNAL per mL urine than whites, while Japanese Americans 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 Native Hawaiian and Latino smokers, respectively. Impact: The higher lung cancer susceptibility of African-American smokers and the lower susceptibility of Japanese-American smokers compared with whites can be explained in part by exposure to the potent lung carcinogen NNK.