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

Abstract

<div>Abstract<p><b>Background:</b> 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 in urine as the corresponding N-acetylcysteine conjugates. We hypothesize that single nucleotide polymorphisms (SNPs) in BD-metabolizing genes may change the balance of BD bioactivation and detoxification in White, Japanese American, and African American smokers, potentially contributing to ethnic differences in lung cancer risk.</p><p><b>Methods:</b> We measured the levels of BD metabolites, 1- and 2-(<i>N</i>-acetyl-L-cysteine-S-yl)-1-hydroxybut-3-ene (MHBMA) and <i>N</i>-acetyl-<i>S</i>-(3,4-dihydroxybutyl)-L-cysteine (DHBMA), in urine samples from a total of 1,072 White, Japanese American, and African American smokers and adjusted these values for body mass index, age, batch, and total nicotine equivalents. We also conducted a genome-wide association study to identify genetic determinants of BD metabolism.</p><p><b>Results:</b> We found that mean urinary MHBMA concentrations differed significantly by ethnicity (<i>P</i> = 4.0 × 10<sup>−25</sup>). African Americans excreted the highest levels of MHBMA followed by Whites and Japanese Americans. MHBMA levels were affected by <i>GSTT1</i> gene copy number (<i>P</i> < 0.0001); conditional on <i>GSTT1</i>, no other polymorphisms showed a significant association. Urinary DHBMA levels also differed between ethnic groups (<i>P</i> = 3.3 × 10<sup>−4</sup>), but were not affected by <i>GSTT1</i> copy number (<i>P</i> = 0.226).</p><p><b>Conclusions:</b> <i>GSTT1</i> gene deletion has a strong effect on urinary MHBMA levels, and therefore BD metabolism, in smokers.</p><p><b>Impact:</b> Our results show that the order of MHBMA levels among ethnic groups is consistent with their respective lung cancer risk and can be partially explained by <i>GSTT1</i> genotype. <i>Cancer Epidemiol Biomarkers Prev; 26(7); 1034–42. ©2017 AACR</i>.</p></div>