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

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

Author information

1
University of Montreal Hospital Research Centre (CRCHUM), Tour Saint-Antoine, 850 rue Saint-Denis, 2nd Floor, S02-344, Montréal, Québec, H2X 0A9, Canada. Electronic address: vikki.ho@umontreal.ca.
2
University of Montreal Hospital Research Centre (CRCHUM), Tour Saint-Antoine, 850 rue Saint-Denis, 2nd Floor, S02-424, Montréal, Québec, H2X 0A9, Canada. Electronic address: vanessa.brunetti.chum@ssss.gouv.qc.ca.
3
Department of Public Health Sciences, 2nd Floor Carruthers Hall, Queen's University, Kingston, Ontario, K7L3N6, Canada. Electronic address: sarah.peacock@queensu.ca.
4
Pharmacology and Toxicology Graduate Program, Department of Biomedical and Molecular Sciences, 5th Floor Botterell Hall, Queen's University, Kingston, Ontario, K7L3N6, Canada. Electronic address: masseyt@queensu.ca.
5
Department of Pharmacology and Toxicology, Maastricht University, Maastricht, PO Box 616, 6200 MD Maastricht, The Netherlands. Electronic address: r.godschalk@maastrichtuniversity.nl.
6
Department of Pharmacology and Toxicology, Maastricht University, Maastricht, PO Box 616, 6200 MD Maastricht, The Netherlands. Electronic address: f.vanschooten@maastrichtuniversity.nl.
7
Department of Public Health Sciences, Carruthers Hall, Queen's University, Kingston, Ontario, K7L3N6, Canada. Electronic address: asburyj@queensu.ca.
8
Gastrointestinal Diseases Research Unit (GIDRU), Queen's University, Kingston, ON, K7L 3N6, Canada. Electronic address: vanners@hdh.kari.net.
9
Department of Public Health Sciences, 2nd Floor Carruthers Hall, Queen's University, Kingston,Ontario, K7L3N6, Canada. Electronic address: kingw@queensu.ca.

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

PMID:
28735743
DOI:
10.1016/j.mrgentox.2017.06.005
[Indexed for MEDLINE]

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