Original Contribution Associations BetweenGenetic Ancestries and Nicotine MetabolismBiomarkers in the Multiethnic Cohort Study

Differences in internal dose of nicotine and tobacco-derived carcinogens among ethnic/racial groups have been observed. In this study, we explicitly examined the relationships between genetic ancestries (genome-wide average) and 19 tobacco-derived biomarkers in smokers from 3 admixed groups in theMultiethnic Cohort Study (1993–present), namely, African ancestry in African Americans (n = 362), Amerindian ancestry in Latinos (n = 437), and Asian and Native Hawaiian ancestries in Native Hawaiians (n = 300). After multiple comparison adjustment, both African and Asian ancestries were significantly related to a greater level of free cotinine; African ancestry was also significantly related to lower cotinine glucuronidation (P ’s < 0.00156). The predicted decrease in cotinine glucuronidation was 8.6% (P = 4.5 × 10) per a 20% increase in African ancestry. Follow-up admixture mapping revealed that African ancestry in a 12-Mb region on chromosome 4qwas related to lower cotinine glucuronidation (P ’s < 2.7 × 10, smallest P = 1.5 × 10), although this is the same region reported in our previous genome-wide association study. Our results implicate a genetic ancestral component in the observed ethnic/racial variation in nicotine metabolism. Further studies are needed to identify the underlying genetic variation that could potentially be ethnic/racial specific.