Benzene Uptake and Glutathione S-transferase T1 Status as Determinants of S-Phenylmercapturic Acid in Cigarette Smokers in the Multiethnic Cohort

PLoS One. 2016 Mar 9;11(3):e0150641. doi: 10.1371/journal.pone.0150641. eCollection 2016.


Research from the Multiethnic Cohort (MEC) demonstrated that, for the same quantity of cigarette smoking, African Americans and Native Hawaiians have a higher lung cancer risk than Whites, while Latinos and Japanese Americans are less susceptible. We collected urine samples from 2,239 cigarette smokers from five different ethnic groups in the MEC and analyzed each sample for S-phenylmercapturic acid (SPMA), a specific biomarker of benzene uptake. African Americans had significantly higher (geometric mean [SE] 3.69 [0.2], p<0.005) SPMA/ml urine than Whites (2.67 [0.13]) while Japanese Americans had significantly lower levels than Whites (1.65 [0.07], p<0.005). SPMA levels in Native Hawaiians and Latinos were not significantly different from those of Whites. We also conducted a genome-wide association study in search of genetic risk factors related to benzene exposure. The glutathione S-transferase T1 (GSTT1) deletion explained between 14.2-31.6% (p = 5.4x10-157) and the GSTM1 deletion explained between 0.2%-2.4% of the variance (p = 1.1x10-9) of SPMA levels in these populations. Ethnic differences in levels of SPMA remained strong even after controlling for the effects of these two deletions. These results demonstrate the powerful effect of GSTT1 status on SPMA levels in urine and show that uptake of benzene in African American, White, and Japanese American cigarette smokers is consistent with their lung cancer risk in the MEC. While benzene is not generally considered a cause of lung cancer, its metabolite SPMA could be a biomarker for other volatile lung carcinogens in cigarette smoke.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetylcysteine / analogs & derivatives*
  • Acetylcysteine / metabolism
  • Aged
  • Benzene / metabolism*
  • Female
  • Genome-Wide Association Study
  • Genotype
  • Glutathione Transferase / metabolism*
  • Humans
  • Male
  • Middle Aged
  • Quality Control
  • Risk Factors
  • Smoking / metabolism*


  • S-phenyl-N-acetylcysteine
  • glutathione S-transferase T1
  • Glutathione Transferase
  • Benzene
  • Acetylcysteine