Linked Life Data

12376500

Source:http://linkedlifedata.com/resource/pubmed/id/12376500

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10 Pt 1
pubmed:dateCreated
2002-10-11
pubmed:abstractText
Cigarette smoking is the main risk factor for bladder cancer, accounting for at least 50% of bladder cancer in men. Cigarette smoke is a rich source of arylamines, which are detoxified by the NAT2 enzyme and activated by the NAT1 enzyme to highly reactive species that can form bulky adducts on DNA. DNA damage from such adducts is mainly repaired by the nucleotide excision repair pathway, in which the XPD protein functions in opening the DNA helix. We hypothesized that an XPD codon 751 polymorphism (Lys-to-Gln amino acid change) could affect the repair of smoking-induced DNA damage and could be associated with bladder-cancer risk. We also hypothesized that allelic variants of the NAT1 and NAT2 genes might modify the effect of the XPD codon 751 polymorphism on smoking-associated bladder-cancer risk. We determined the XPD codon 751 genotype for 228 bladder-cancer cases and 210 controls who were frequency-matched to cases by age, sex, and ethnicity, and we used our previously published data on the NAT1 and NAT2 genotypes for these same individuals (J. A. Taylor et al., Cancer Res., 58: 3603-3610, 1998). We found a slight decrease in risk for the XPD codon 751 Gln/Gln genotype (adjusted odds ratio: 0.8; 95% confidence interval: 0.4-1.3) compared with subjects with the Lys/Lys or Lys/Gln genotypes. The analysis with smoking showed that smokers with the Lys/Lys or Lys/Gln genotypes were twice as likely to have bladder cancer than smokers with the Gln/Gln genotype (test of interaction P = 0.03). The combined presence of the NAT1/NAT2 high-risk genotype and the XPD Lys/Lys or Lys/Gln genotypes ignoring smoking had an odds ratio that was only slightly higher than expected, assuming no genotype-genotype interaction (P = 0.52). We found little evidence for a gene-gene-exposure, three-way interaction among the XPD codon 751 genotype, smoking, and the NAT1/NAT2 genotype.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1055-9965
pubmed:author
pubmed:issnType
Print
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1004-11
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:12376500-Aged, pubmed-meshheading:12376500-Arylamine N-Acetyltransferase, pubmed-meshheading:12376500-Case-Control Studies, pubmed-meshheading:12376500-DNA Adducts, pubmed-meshheading:12376500-DNA Damage, pubmed-meshheading:12376500-DNA Helicases, pubmed-meshheading:12376500-DNA Repair, pubmed-meshheading:12376500-DNA-Binding Proteins, pubmed-meshheading:12376500-Female, pubmed-meshheading:12376500-Genetic Predisposition to Disease, pubmed-meshheading:12376500-Genotype, pubmed-meshheading:12376500-Humans, pubmed-meshheading:12376500-Isoenzymes, pubmed-meshheading:12376500-Male, pubmed-meshheading:12376500-Middle Aged, pubmed-meshheading:12376500-Odds Ratio, pubmed-meshheading:12376500-Polymorphism, Genetic, pubmed-meshheading:12376500-Proteins, pubmed-meshheading:12376500-Risk Factors, pubmed-meshheading:12376500-Smoking, pubmed-meshheading:12376500-Transcription Factors, pubmed-meshheading:12376500-Urinary Bladder Neoplasms, pubmed-meshheading:12376500-Xeroderma Pigmentosum Group D Protein
pubmed:year
2002
pubmed:articleTitle
XPD codon 751 polymorphism, metabolism genes, smoking, and bladder cancer risk.
pubmed:affiliation
Molecular and Genetic Epidemiology Section, Laboratory of Molecular Carcinogenesis and the National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina, 27709, USA.
pubmed:publicationType
Journal Article