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.