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dc.contributor.authorGarcía-Closas, Men_US
dc.contributor.authorHein, DWen_US
dc.contributor.authorSilverman, Den_US
dc.contributor.authorMalats, Nen_US
dc.contributor.authorYeager, Men_US
dc.contributor.authorJacobs, Ken_US
dc.contributor.authorDoll, MAen_US
dc.contributor.authorFigueroa, JDen_US
dc.contributor.authorBaris, Den_US
dc.contributor.authorSchwenn, Men_US
dc.contributor.authorKogevinas, Men_US
dc.contributor.authorJohnson, Aen_US
dc.contributor.authorChatterjee, Nen_US
dc.contributor.authorMoore, LEen_US
dc.contributor.authorMoeller, Ten_US
dc.contributor.authorReal, FXen_US
dc.contributor.authorChanock, Sen_US
dc.contributor.authorRothman, Nen_US
dc.identifier.citationPharmacogenetics and genomics, 2011, 21 (4), pp. 231 - 236en_US
dc.description.abstractThe arylamine N-acetyltransferase 2 (NAT2) slow acetylation phenotype is an established risk factor for urinary bladder cancer. We reported earlier on this risk association using NAT2 phenotypic categories inferred from NAT2 haplotypes based on seven single nucleotide polymorphisms (SNPs) in a study in Spain. In a subsequent genome-wide scan, we have identified a single common tag SNP (rs1495741) located in the 3' end of NAT2 that is also associated with bladder cancer risk. The aim of this report is to evaluate the agreement between the common tag SNP and the 7-SNP NAT2 inferred phenotype. The agreement between the 7-SNP NAT2 inferred phenotype and the tag SNP, rs1495741, was initially assessed in 2174 individuals from the Spanish Bladder Cancer Study (SBCS), and confirmed in a subset of individuals from the Main and Vermont component the New England Bladder Cancer Study (NEBCS). We also investigated the association of rs1495741 genotypes with NAT2 catalytic activity in cryopreserved hepatocytes from 154 individuals of European background. We observed very strong agreement between rs1495741 and the 7-SNP inferred NAT2 phenotype: sensitivity and specificity for the NAT2 slow phenotype was 99 and 95%, respectively. Our findings were replicated in an independent population from the NEBCS. Estimates for the association between NAT2 slow phenotype and bladder cancer risk in the SBCS and its interaction with cigarette smoking were comparable for the 7-SNP inferred NAT2 phenotype and rs1495741. In addition, rs1495741 genotypes were strongly related to NAT2 activity measured in hepatocytes (P<0.0001). A novel NAT2 tag SNP (rs1495741) predicts with high accuracy the 7-SNP inferred NAT2 phenotype, and thus can be used as a sole marker in pharmacogenetic or epidemiological studies of populations of European background. These findings illustrate the utility of tag SNPs, often used in genome-wide association studies (GWAS), to identify novel phenotypic markers. Further studies are required to determine the functional implications of rs1495741 and the structure and evolution of the haplotype on which it resides.en_US
dc.format.extent231 - 236en_US
dc.subjectArylamine N-Acetyltransferaseen_US
dc.subjectCase-Control Studiesen_US
dc.subjectPolymorphism, Single Nucleotideen_US
dc.subjectEuropean Continental Ancestry Groupen_US
dc.subjectNew Englanden_US
dc.titleA single nucleotide polymorphism tags variation in the arylamine N-acetyltransferase 2 phenotype in populations of European background.en_US
dc.typeJournal Article
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfPharmacogenetics and genomicsen_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Molecular Epidemiology
pubs.embargo.termsNot knownen_US
icr.researchteamMolecular Epidemiologyen_US
dc.contributor.icrauthorGarcia-Closas, Montserraten_US

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