Mercapturic acids derived from the toxicants acrolein and crotonaldehyde in the urine of cigarette smokers from five ethnic groups with differing risks for lung cancer

Sungshim L. Park, Steven G. Carmella, Menglan Chen, Yesha Patel, Daniel O. Stram, Christopher A. Haiman, Loic Le Marchand, Stephen S. Hecht

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47 Scopus citations


The Multiethnic Cohort epidemiology study has clearly demonstrated that, compared to Whites and for the same number of cigarettes smoked, African Americans and Native Hawaiians have a higher risk for lung cancer whereas Latinos and Japanese Americans have a lower risk. Acrolein and crotonaldehyde are two important constituents of cigarette smoke which have well documented toxic effects and could play a role in lung cancer etiology. Their urinary metabolites 3-hydroxypropylmercapturic acid (3-HPMA) and 3-hydroxy-1- methylpropylmercapturic acid (HMPMA), respectively, are validated biomarkers of acrolein and crotonaldehyde exposure. We quantified levels of 3-HPMA and HMPMA in the urine of more than 2200 smokers from these five ethnic groups, and also carried out a genome wide association study using blood samples from these subjects. After adjusting for age, sex, creatinine, and total nicotine equivalents, geometric mean levels of 3-HPMA and HMPMA were significantly different in the five groups (P<0.0001). Native Hawaiians had the highest and Latinos the lowest geometric mean levels of both 3-HPMA and HMPMA. Levels of 3- HPMA and HMPMA were 3787 and 2759 pmol/ml urine, respectively, in Native Hawaiians and 1720 and 2210 pmol/ml urine in Latinos. These results suggest that acrolein and crotonaldehyde may be involved in lung cancer etiology, and that their divergent levels may partially explain the differing risks of Native Hawaiian and Latino smokers. No strong signals were associated with 3-HPMA in the genome wide association study, suggesting that formation of the glutathione conjugate of acrolein is mainly non-enzymatic, while the top significant association with HMPMA was located on chromosome 12 near the TBX3 gene, but its relationship to HMPMA excretion is not clear.

Original languageEnglish (US)
Article numbere0124841
JournalPloS one
Issue number6
StatePublished - Jun 8 2015

Bibliographical note

Funding Information:
This study was supported by grant no. CA-138338 and in part by grant no. CA-14089 from the U.S. National Cancer Institute ( ). Mass spectrometry was carried out in the Analytical Biochemistry Shared Resource of the Masonic Cancer Center, supported in part by National Cancer Institute Cancer Center Support grant no. CA-77598.

Publisher Copyright:
© 2015 Park et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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