BACKGROUND: Identifying sources of variation in the @entity1239 and @entity22463 metabolic inactivation pathways is important to understanding the relationship between smoking and @entity5 risk. Numerous UGT1A and UGT2B enzymes are implicated in @entity1239 and @entity22463 metabolism in vitro; however, little is known about their roles in vivo. METHODS: Within UGT1A1, UGT1A4, UGT1A9, UGT2B7, UGT2B10, and UGT2B17, 47 variants were genotyped, including UGT2B10*2 and UGT2B17*2. The association between variation in these UGTs and glucuronidation activity within European and African American current smokers (n = 128), quantified as urinary ratios of the glucuronide over unconjugated compound for @entity1239 , @entity4874 , @entity5943 , and @entity68152 (NNAL), was investigated in regression models assuming a dominant effect of variant alleles. RESULTS: Correcting for multiple testing, three UGT2B10 variants were associated with @entity4874 glucuronidation, @entity68153 and @entity68154 in European Americans and @entity68155 in African Americans (P  <= 0.0002). Additional variants predominantly in UGT2B10 were nominally associated with @entity1239 (P = 0.008-0.04) and @entity4874 (P = <0.001-0.02) glucuronidation in both ethnicities in addition to UGT2B10*2 in European Americans (P = 0.01, P < 0.001). UGT2B17*2 (P = 0.03) in European Americans and UGT2B7 variants (P = 0.02-0.04) in African Americans were nominally associated with 3HC glucuronidation. UGT1A (P = 0.007-0.01), UGT2B10 (P = 0.02), and UGT2B7 (P = 0.02-0.03) variants in African Americans were nominally associated with NNAL glucuronidation. CONCLUSIONS: Findings from this initial in vivo study support a role for multiple UGTs in the glucuronidation of @entity286 -related compounds in vivo, in particular UGT2B10 and @entity4874 glucuronidation. IMPACT: Findings also provide insight into ethnic differences in glucuronidation activity, which could be contributing to ethnic disparities in the risk for smoking-related @entity5 . Cancer Epidemiol Biomarkers Prev; 24(1); 1-11.   2014 AACR.

UGT1A and UGT2B Genetic Variation Alters XXXX and @entity22463 Glucuronidation in European and African American Smokers.

@entity286 :: ('4097', 'Species') :: ['tobacco'] @entity68155 :: ('rs835309', 'SNP') :: ['rs835309'] @entity68152 :: ('MESH:C475721', 'Chemical') :: ['4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol'] @entity68153 :: ('rs2331559', 'SNP') :: ['rs2331559'] @entity5 :: ('MESH:D009369', 'Disease') :: ['cancers', 'cancer'] @entity1239 :: ('MESH:D009538', 'Chemical') :: ['nicotine'] @entity4874 :: ('MESH:D003367', 'Chemical') :: ['cotinine'] @entity5943 :: ('MESH:C001381', 'Chemical') :: ["trans-3'-hydroxycotinine"] @entity22463 :: ('CHEBI:35803', 'Chemical') :: ['nitrosamine'] @entity68154 :: ('rs11726322', 'SNP') :: ['rs11726322']
@entity1239 :: (MESH:D009538,Chemical) :: ['Nicotine']
