Bulky DNA adduct levels in normal-appearing colon mucosa, and the prevalence of colorectal adenomas

Vikki Ho*, Sarah Peacock, Thomas E. Massey, Roger W. Godschalk, Frederik J. van Schooten, Janet E. Ashbury, Stephen J. Vanner, Will D. King

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Web of Science)

Abstract

Purpose: Examine the association between bulky DNA adduct levels in colon mucosa and colorectal adenoma prevalence, and explore the correlation between adduct levels in leukocytes and colon tissue. Methods: Bulky DNA adduct levels were measured using P-32-postlabelling in biopsies of normal-appearing colon tissue and blood donated by 202 patients. Multivariable logistic regression was used to examine associations between DNA adducts, and interactions of DNA adduct-DNA repair polymorphisms, with the prevalence of colorectal adenomas. Correlation between blood and tissue levels of DNA adducts was evaluated using Spearman's correlation coefficient. Results: An interaction between bulky DNA adduct levels and XPA rs1800975 on prevalence of colorectal adenoma was observed. Among individuals with lower DNA repair activity, increased DNA adduct levels were associated with increased colorectal adenoma prevalence (OR = 1.41 per SD increase, 95%CI: 0.92-2.18). Conversely, among individuals with normal DNA activity, an inverse association was observed (OR = 0.60 per SD increase, 95%CI: 0.34-1.07). Blood and colon DNA adduct levels were inversely correlated (rho = -0.20). Conclusions: Among genetically susceptible individuals, higher bulky DNA adducts in the colon was associated with the prevalence of colorectal adenomas. The inverse correlation between blood and colon tissue measures demonstrates the importance of quantifying biomarkers in target tissues.
Original languageEnglish
Pages (from-to)735-741
Number of pages7
JournalBiomarkers
Volume23
Issue number8
DOIs
Publication statusPublished - 17 Nov 2018

Keywords

  • Colorectal cancer
  • genotoxicity
  • DNA adducts
  • 32P-postlabelling
  • DNA repair
  • genetic polymorphisms
  • HETEROCYCLIC AROMATIC-AMINES
  • CANCER-RISK
  • MASS-SPECTROMETRY
  • GENETIC POLYMORPHISMS
  • IN-VITRO
  • REPAIR
  • IDENTIFICATION
  • QUANTITATION
  • METABOLISM
  • EXPOSURE

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