title: Benzene Uptake and Glutathione S-transferase T1 Status as Determinants of S-Phenylmercapturic Acid in Cigarette Smokers in the Multiethnic Cohort.
abstract: 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.
authors.affiliation: Department of Preventive Medicine and Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90032, United States of America.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Haiman
authors.affiliation: Department of Preventive Medicine and Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90032, United States of America.
authors.forename: Yesha M
authors.initials: YM
authors.lastname: Patel
authors.affiliation: Department of Preventive Medicine and Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90032, United States of America.
authors.forename: Daniel O
authors.initials: DO
authors.lastname: Stram
authors.affiliation: Masonic Cancer Center, University of Minnesota, Minneapolis, MN, 55105, United States of America.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Carmella
authors.affiliation: Masonic Cancer Center, University of Minnesota, Minneapolis, MN, 55105, United States of America.
authors.forename: Menglan
authors.initials: M
authors.lastname: Chen
authors.affiliation: Epidemiology Program, Cancer Research Center of Hawai'i, University of Hawai'i, Honolulu, HI, 96813, United States of America.
authors.forename: Lynne R
authors.initials: LR
authors.lastname: Wilkens
authors.affiliation: Epidemiology Program, Cancer Research Center of Hawai'i, University of Hawai'i, Honolulu, HI, 96813, United States of America.
authors.forename: Loic
authors.initials: L
authors.lastname: Le Marchand
authors.affiliation: Masonic Cancer Center, University of Minnesota, Minneapolis, MN, 55105, United States of America.
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Hecht
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000378:metabolism; D000368:Aged; D001554:Benzene / Q000378:metabolism*; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D005982:Glutathione Transferase / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011786:Quality Control; D012307:Risk Factors; D012907:Smoking / Q000378:metabolism*
chemical_list: C053003:S-phenyl-N-acetylcysteine; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase; D001554:Benzene; D000111:Acetylcysteine