1,3-Butadiene exposure and metabolism among Japanese American, Native Hawaiian, and White smokers

Background: We hypothesize that the differences in lung Cancer risk in Native Hawaiians, whites, and Japanese Americans may, in part, be due to variation in the metabolism of 1,3-butadiene, one of the most abundant carcinogens in cigarette smoke.

Methods: We measured two biomarkers of 1,3-butadiene exposure, monohydroxybutyl mercapturic acid (MHBMA) and dihydroxybutyl mercapturic acid (DHBMA), in overnight urine samples among 584 Native Hawaiians, Japanese Americans, and white smokers in Hawaii. These values were normalized to creatinine levels. Ethnic-specific geometric means were compared adjusting for age at urine collection, sex, body mass index, and nicotine equivalents (a marker of total nicotine uptake).

Results: We found that mean urinary MHBMA differed by race/ethnicity (P = 0.0002). The values were highest in whites and lowest in Japanese Americans. This difference was only observed in individuals with the GSTT1-null genotype (P = 0.0001). No difference across race/ethnicity was found among those with at least one copy of the GSTT1 gene (P ≥ 0.72). Mean urinary DHBMA did not differ across racial/ethnic groups.

Conclusions: The difference in urinary MHBMA excretion levels from cigarette smoking across three ethnic groups is, in part, explained by the GSTT1 genotype. Mean urinary MHBMA levels are higher in whites among GSTT1-null smokers.

Impact: The overall higher excretion levels of MHBMA in whites and lower levels of MHBMA in Japanese Americans are consistent with the higher lung Cancer risk in the former. However, the excretion levels of MHBMA in Native Hawaiians are not consistent with their disease risk and thus unlikely to explain their high risk of lung Cancer.