Determining the best model to explain inter-individual variations in PAH-DNA adduct levels among non-smokers

Tuesday, October 25, 2011 — Poster Session II
Noon – 2:00 p.m.	Natcher Conference Center	NCI	GEN/GENOM-5

Authors

• A Etemadi
• F Islami
• FJ van Schooten
• D Phillips
• F Kamangar
• C Abnet
• A Golozar
• R Godschalk
• P Boffetta
• R Malekzadeh
• S Dawsey

Abstract

The aim of this study was to assess the genetic and environmental factors affecting inter-individual variability in the blood level of polycyclic aromatic hydrocarbon (PAH)-DNA adducts. Among participants in the Golestan Cohort Study, 111 female non-smokers were randomly selected. Twenty-one SNPs in 14 genes related to xenobiotic metabolism and 12 SNPs in eight DNA repair genes were studied. NER capacity was evaluated by the comet assay, and DNA adduct level was measured by 32-p postlabeling. Multivariate regression was used to assess the simultaneous effects of the number of mutant SNPs in each gene, NER capacity, and environmental exposures on the PAH-DNA adduct levels. Models were compared by Akaike’s information criterion (AIC). The model including environmental exposures, phase 1 xenobiotic metabolism SNPs and NER capacity had the lowest AIC. Among all SNPs, NA2 (b=-0.21; p<0.05), myeloperoxidase (b=-0.17; p<0.05) and ERCC-5 genes (b=0.15, p<0.05) had significant associations with PAH-DNA adduct levels. NER capacity itself was affected by a polymorphism in the methylenetetrahydrofolate reductase gene (b=0.41, p<0.01). A combination of environmental factors, number of polymorphisms in phase 1 xenobiotic metabolism genes and DNA repair capacity can best explain inter-individual variability in PAH-DNA adduct levels.

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