Dissemin is shutting down on January 1st, 2025

Published in

American Association for Cancer Research, Cancer Research, 8_Supplement(72), p. 2646-2646, 2012

DOI: 10.1158/1538-7445.am2012-2646

Links

Tools

Export citation

Search in Google Scholar

Abstract 2646: Genetic determinants of PAH-DNA adduct level and nucleotide excision repair among non-smokers in a high risk area for esophageal squamous cell carcinoma

This paper was not found in any repository, but could be made available legally by the author.
This paper was not found in any repository, but could be made available legally by the author.

Full text: Unavailable

Green circle
Preprint: archiving allowed
Orange circle
Postprint: archiving restricted
Red circle
Published version: archiving forbidden
Data provided by SHERPA/RoMEO

Abstract

Abstract Background: Polycyclic aromatic hydrocarbons (PAHs) play a role in esophageal squamous cell carcinoma in high risk areas where even non-smokers are highly exposed to these compounds. Their early biological effect is the formation of DNA adducts, mediated by phase 1 and 2 pathways and nucleotide excision repair (NER). We aimed at finding a genetic model to explain inter-individual variations in PAH-DNA adduct level among people with similar exposures. Methods: In 111 randomly-selected female non-smokers from the Golestan Cohort Study in Iran, 21 SNPs in 14 genes related to xenobiotic metabolism and 13 SNPs in 9 DNA repair genes were studied (Table). NER capacity was evaluated by a comet assay, and DNA adduct level was measured by 32p-postlabelling. Multivariate regression was used to assess the effects of the number of risk alleles, NER capacity, and environmental exposures on the log-transformed PAH-DNA adduct levels. Models were compared by Akaike's information criterion (AIC). Results: Mean PAH-DNA adduct level was 5.76+3.13 per 108 nucleotides (range: 1.71 - 18.57). The level of PAH-DNA adducts was significantly lower in homozygotes for N-acetyltransferase 2 (NAT2) slow alleles and excision repair cross-complementing (ERCC)-5 T/T genotype, and higher in individuals with myeloperoxidase (MPO) G/G genotype. The sum of risk alleles in these genes had a significant correlation with the log-adduct level (r=0.4, p<0.001). The table shows gene level coefficients for multivariate analysis. The model including environmental exposures, phase 1 SNPs and NER capacity had the best fit (AIC=93.7). NER capacity itself was affected by a polymorphism in the methylenetetrahydrofolate reductase gene. Conclusion: We observed a high level of PAH-DNA adducts with great inter-individual variation, which could be best explained by a combination of environmental factors, number of polymorphisms in phase 1 genes and DNA repair capacity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2646. doi:1538-7445.AM2012-2646