Publications Repository

Publications Repository

View item 
  •   Home
  • ICR Divisions
  • Closed Research Teams
  • View item
  • Home
  • ICR Divisions
  • Closed Research Teams
  • View item
JavaScript is disabled for your browser. Some features of this site may not work without it.

A single nucleotide polymorphism tags variation in the arylamine N-acetyltransferase 2 phenotype in populations of European background.

Thumbnail
Date
2011-04
ICR Author
Garcia-Closas, Montserrat
Author
García-Closas, M
Hein, DW
Silverman, D
Malats, N
Yeager, M
Jacobs, K
Doll, MA
Figueroa, JD
Baris, D
Schwenn, M
Kogevinas, M
Johnson, A
Chatterjee, N
Moore, LE
Moeller, T
Real, FX
Chanock, S
Rothman, N
Show allShow less
Type
Journal Article
Metadata
Show full item record
Abstract
The 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.
URI
https://repository.icr.ac.uk/handle/internal/2336
DOI
https://doi.org/10.1097/fpc.0b013e32833e1b54
Collections
  • Closed Research Teams
Subject
Humans
Arylamine N-Acetyltransferase
Case-Control Studies
Genotype
Haplotypes
Phenotype
Polymorphism, Single Nucleotide
European Continental Ancestry Group
New England
Vermont
Spain
Research team
Molecular Epidemiology
Language
eng
License start date
2011-04
Citation
Pharmacogenetics and genomics, 2011, 21 (4), pp. 231 - 236

Browse

All of ICR repositoryICR DivisionsBy issue dateAuthorsTitlesPublication TypesThis collectionBy issue dateAuthorsTitlesPublication Types
  • Login
  • Registered office: The Institute of Cancer Research, 123 Old Brompton Road, London, SW7 3RP
    A Charity, Not for Profit. Company Limited by Guarantee.
    Registered in England No. 534147. VAT Registration No. GB 849 0581 02.