Exposure to meat-derived carcinogens and bulky DNA adduct levels in normal-appearing colon mucosa

Mutat Res. 2017 Sep;821:5-12. doi: 10.1016/j.mrgentox.2017.06.005. Epub 2017 Jul 4.

Abstract

Introduction: Meat consumption is a risk factor for colorectal cancer. This research investigated the relationship between meat-derived carcinogen exposure and bulky DNA adduct levels, a biomarker of DNA damage, in colon mucosa.

Methods: Least squares regression was used to examine the relationship between meat-derived carcinogen exposure (PhIP and meat mutagenicity) and bulky DNA adduct levels in normal-appearing colon tissue measured using 32P-postlabelling among 202 patients undergoing a screening colonoscopy. Gene-diet interactions between carcinogen exposure and genetic factors relevant to biotransformation and DNA repair were also examined. Genotyping was conducting using the MassARRAY® iPLEX® Gold SNP Genotyping assay.

Results: PhIP and higher meat mutagenicity exposures were not associated with levels of bulky DNA adducts in colon mucosa. The XPC polymorphism (rs2228001) was found to associate with bulky DNA adduct levels, whereby genotypes conferring lower DNA repair activity were associated with higher DNA adduct levels than the normal activity genotype. Among individuals with genotypes associated with lower DNA repair (XPD, rs13181 and rs1799179) or detoxification activity (GSTP1, rs1695), higher PhIP or meat mutagenicity exposures were associated with higher DNA adduct levels. Significant interactions between the XPC polymorphism (rs2228000) and both dietary PhIP and meat mutagenicity on DNA adduct levels was observed, but associations were inconsistent with the a priori hypothesized direction of effect.

Conclusion: Exposure to meat-derived carcinogens may be associated with increased DNA damage occurring directly in the colon among genetically susceptible individuals.

Keywords: Colon; DNA adducts; Meat mutagenicity; PhIP; Polymorphism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biotransformation
  • Carcinogens / metabolism
  • Carcinogens / pharmacokinetics
  • Carcinogens / toxicity*
  • Colon / drug effects*
  • Colon / metabolism
  • Colon / pathology
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Colonoscopy
  • Cross-Sectional Studies
  • DNA Adducts / genetics
  • DNA Adducts / metabolism*
  • Diet
  • Female
  • Gene-Environment Interaction
  • Humans
  • Imidazoles / metabolism*
  • Imidazoles / pharmacokinetics
  • Imidazoles / toxicity*
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Irritable Bowel Syndrome / metabolism
  • Irritable Bowel Syndrome / pathology
  • Male
  • Meat / analysis*
  • Middle Aged
  • Polymorphism, Genetic

Substances

  • 2-amino-1-methyl-6-phenolimidazo(4,5-b)pyridine-DNA adduct
  • Carcinogens
  • DNA Adducts
  • Imidazoles
  • 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine