1,3-Butadiene Exposure and Metabolism among Japanese American, Native Hawaiian, and White Smokers

Abstract

Background We hypothesize that the differences in lung cancer risk in Native Hawaiians (NH), whites and Japanese Americans (JA), may in part be due to variation in the metabolism of 1,3-butadiene (BD), one of the most abundant carcinogens in cigarette smoke. Methods We measured two biomarkers of BD exposure, monohydroxybutyl mercapturic acid (MHBMA) and dihydroxybutyl mercapturic acid (DHBMA) in overnight urine samples among 585 NH, JA 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 JA. 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 JA are consistent with the higher lung cancer risk in the former. However, the excretion levels of MHBMA in NH are not consistent with and, thus, unlikely to explain, their high risk of lung cancer.

Genetic Determinants of 1,3-Butadiene Metabolism and Detoxification in Three Populations of Smokers with Different Risks of Lung Cancer

“…This is consistent with our recent small study of White, Native Hawaiian, and Japanese smokers, which also reported the lowest MHBMA levels from individuals with the GSTT1 deletion, followed by those with one and two copies of the gene (9). Adjusting for GSTT1 deletion explained the difference in urinary MHBMA between Japanese Americans and Whites; however, the difference between Whites and African Americans remained (Table 4).…”

“…Urinary concentrations of MHBMA and DHBMA were determined using previously published HPLC-ESI - -MS/MS methods described in Supplement S1 (9,53). Samples that showed no MHBMA or DHBMA signal were assigned a value corresponding to the limit of detection divided by 2 (0.1 ng/mL urine for MHBMA [9 samples] and 2.5 ng/mL urine for DHBMA [2 samples]).…”

Isotope Dilution nanoLC/ESI+-HRMS3 Quantitation of Urinary N7-(1-Hydroxy-3-buten-2-yl) Guanine Adducts in Humans and Their Use as Biomarkers of Exposure to 1,3-Butadiene

“…These results are similar to those previously reported by our laboratory, in which European American smokers were found to have significantly higher urinary concentrations of MHBMA as compared to Native Hawaiian and Japanese American smokers, whereas urinary DHBMA concentrations did not significantly differ between these groups. 53 …”

Tobacco, e-cigarettes, and child health

“…This is a situation where biomarkers studies might provide insight into the tobacco smoke chemicals that are contributing to the adverse birth outcomes. For example, GSTT1 null genotype influences the levels of urinary benzene and 1,3-butadiene metabolites in smokers [22,23]. CYP1A1 and GSTT1 variants affect metabolite levels of a model polycyclic aromatic hydrocarbon, phenanthrene [24,25].…”