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Nucleotide excision repair gene polymorphisms and risk of advanced colorectal adenoma: XPC polymorphisms modify smoking-related risk

Cited 74 time in Web of Science Cited 77 time in Scopus
Authors
Huang, Wen-Yi; Berndt, Sonja I.; Kang, Daehee; Chatterjee, Nilanjan; Chanock, Stephen J.; Yeager, Meredith; Welch, Robert; Bresalier, Rober S.; Weissfeld, Joel L.; Hayes, Richard B.
Issue Date
2006-02-24
Publisher
American Association for Cancer Research
Citation
Cancer Epidemiol Biomarkers Prev. 2006 Feb;15(2):306-11.
Keywords
Adenoma/*geneticsAgedAllelesCase-Control StudiesColorectal Neoplasms/*geneticsDNA Helicases/geneticsDNA Repair/*geneticsDNA-Binding Proteins/*geneticsFemaleGenotypeHumansLinkage DisequilibriumLogistic ModelsMaleMiddle AgedMultivariate Analysis*Polymorphism, Single NucleotideRisk FactorsSmoking/adverse effects/*genetics
Abstract
OBJECTIVES: Nucleotide excision repair enzymes remove bulky damage caused by environmental agents, including carcinogenic polycyclic aromatic hydrocarbons found in cigarette smoke, a risk factor for colorectal adenoma. Among participants randomized to the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, we studied the risk of advanced colorectal adenoma in relation to cigarette smoking and selected single nucleotide polymorphisms (SNP) in the nucleotide excision repair pathway.METHODS: Cases (n = 772) were subjects with left-sided advanced adenoma (>1 cm in size, high-grade dysplasia, or villous characteristics). Controls (n = 777) were screen-negative for left-sided polyps by sigmoidoscopy. DNA was extracted from blood samples and 15 common nonsynonymous SNPs in seven-nucleotide excision repair genes [XPC, RAD23B (hHR23B), CSB (ERCC6), XPD (ERCC2), CCNH, XPF (ERCC4), and XPG (ERCC5)] were genotyped.RESULTS: None of the studied SNPs were independently associated with advanced adenoma risk. Smoking was related to adenoma risk and XPC polymorphisms (R492H, A499V, K939Q) modified these effects (P(interaction) from 0.03-0.003). Although the three XPC variants were in linkage disequilibrium, a multivariate logistic regression tended to show independent protective effects for XPC 499V (P(trend) = 0.06), a finding supported by haplotype analysis (covariate-adjusted global permutation P = 0.03).CONCLUSIONS: Examining a spectrum of polymorphic variants in nucleotide excision repair genes, we found evidence that smoking-associated risks for advanced colorectal adenoma are modified by polymorphisms in XPC, particularly haplotypes containing XPC 499V.
ISSN
1055-9965 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16492920

https://hdl.handle.net/10371/28303
DOI
https://doi.org/10.1158/1055-9965.EPI-05-0751
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College of Medicine/School of Medicine (의과대학/대학원)Preventive Medicine (예방의학전공)Journal Papers (저널논문_예방의학전공)
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