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

摘要: Background: 1,3-Butadiene (BD) is an important carcinogen in tobacco smoke that undergoes metabolic activation to DNA-reactive epoxides. These species can be detoxified via glutathione conjugation and excreted urine as the corresponding N-acetylcysteine conjugates. We hypothesize single nucleotide polymorphisms (SNPs) BD-metabolizing genes may change balance of BD bioactivation detoxification White, Japanese American, African American smokers, potentially contributing ethnic differences lung cancer risk. Methods: measured levels metabolites, 1- 2-( N -acetyl-L-cysteine-S-yl)-1-hydroxybut-3-ene (MHBMA) -acetyl- S -(3,4-dihydroxybutyl)-L-cysteine (DHBMA), samples from a total 1,072 smokers adjusted these values for body mass index, age, batch, nicotine equivalents. also conducted genome-wide association study identify genetic determinants metabolism. Results: found mean urinary MHBMA concentrations differed significantly by ethnicity ( P = 4.0 × 10 −25 ). Americans highest followed Whites Americans. were affected GSTT1 gene copy number , no other showed significant association. Urinary DHBMA between groups 3.3 −4 ), but not 0.226). Conclusions: deletion has strong effect on levels, therefore metabolism, smokers. Impact: Our results show order among consistent with their respective risk partially explained genotype. Cancer Epidemiol Biomarkers Prev; 26(7); 1–9. ©2017 AACR.