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

Wen Yi Huang, Sonja I. Berndt, Daehee Kang, Nilanjan Chatterjee, Stephen J. Chanock, Meredith Yeager, Robert Welch, Robert S. Bresalier, Joel L. Weissfeld, Richard B. Hayes

Research output: Contribution to journalArticlepeer-review

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 (Pinteraction 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 (Ptrend = 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.

Original languageEnglish (US)
Pages (from-to)306-311
Number of pages6
JournalCancer Epidemiology Biomarkers and Prevention
Volume15
Issue number2
DOIs
StatePublished - Feb 2006

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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