title: Associations Between Genetic Ancestries and Nicotine Metabolism Biomarkers in the Multiethnic Cohort Study.
abstract: 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 the Multiethnic 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(-6)) per a 20% increase in African ancestry. Follow-up admixture mapping revealed that African ancestry in a 12-Mb region on chromosome 4q was related to lower cotinine glucuronidation (P's < 2.7 × 10(-7), smallest P = 1.5 × 10(-9)), 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.
authors.forename: Hansong
authors.initials: H
authors.lastname: Wang
authors.forename: Sungshim L
authors.initials: SL
authors.lastname: Park
authors.forename: Daniel O
authors.initials: DO
authors.lastname: Stram
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Haiman
authors.forename: Lynne R
authors.initials: LR
authors.lastname: Wilkens
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Hecht
authors.forename: Laurence N
authors.initials: LN
authors.lastname: Kolonel
authors.forename: Sharon E
authors.initials: SE
authors.lastname: Murphy
authors.forename: Loïc
authors.initials: L
authors.lastname: Le Marchand
mesh_terms: D001741:Black or African American / Q000235:genetics; D000368:Aged; D044466:Asian People / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D003367:Cotinine / Q000097:blood; D005260:Female; D006801:Humans; D007198:Indians, North American / Q000235:genetics; D008297:Male; D008875:Middle Aged; D044468:Native Hawaiian or Pacific Islander / Q000235:genetics; D009538:Nicotine / Q000378:metabolism*; D009602:Nitrosamines / Q000097:blood; D044469:Racial Groups / Q000235:genetics*; D012907:Smoking / Q000097:blood; D044465:White People / Q000235:genetics
chemical_list: D015415:Biomarkers; D009602:Nitrosamines; D009538:Nicotine; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; D003367:Cotinine
keywords: Hispanics; Pacific Islanders; association study; blacks; health disparity; nicotine addiction