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Variation in PAH-related DNA adduct levels among non-smokers: The role of multiple genetic polymorphisms and nucleotide excision repair phenotype

Etemadi, A. and Islami, F. and Phillips, D.H. and Godschalk, R. and Golozar, A. and Kamangar, F. and Malekshah, A.F.T. and Pourshams, A. and Elahi, S. and Ghojaghi, F. and Strickland, P.T. and Taylor, P.R. and Boffetta, P. and Abnet, C.C. and Dawsey, S.M. and Malekzadeh, R. and Van Schooten, F.J. (2013) Variation in PAH-related DNA adduct levels among non-smokers: The role of multiple genetic polymorphisms and nucleotide excision repair phenotype. International Journal of Cancer, 132 (12). pp. 2738-2747.

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Abstract

Polycyclic aromatic hydrocarbons (PAHs) likely play a role in many cancers even in never-smokers. We tried to find a model to explain the relationship between variation in PAH-related DNA adduct levels among people with similar exposures, multiple genetic polymorphisms in genes related to metabolic and repair pathways, and nucleotide excision repair (NER) capacity. In 111 randomly selected female never-smokers from the Golestan Cohort Study in Iran, we evaluated 21 SNPs in 14 genes related to xenobiotic metabolism and 12 SNPs in eight DNA repair genes. NER capacity was evaluated by a modified comet assay, and aromatic DNA adduct levels were measured in blood by32P-postlabeling. Multivariable regression models were compared by Akaike's information criterion (AIC). Aromatic DNA adduct levels ranged between 1.7 and 18.6 per 108 nucleotides (mean: 5.8 ± 3.1). DNA adduct level was significantly lower in homozygotes for NAT2 slow alleles and ERCC5 non-risk-allele genotype, and was higher in the MPO homozygote risk-allele genotype. The sum of risk alleles in these genes significantly correlated with the log-adduct level (r = 0.4, p < 0.001). Compared with the environmental model, adding Phase I SNPs and NER capacity provided the best fit, and could explain 17 more of the variation in adduct levels. NER capacity was affected by polymorphisms in the MTHFR and ERCC1 genes. Female non-smokers in this population had PAH-related DNA adduct levels three to four times higher than smokers and occupationally-exposed groups in previous studies, with large inter-individual variation which could best be explained by a combination of Phase I genes and NER capacity. Copyright © 2012 UICC.

Item Type: Article
Additional Information: cited By 3
Uncontrolled Keywords: 5,10 methylenetetrahydrofolate reductase (FADH2); arylamine acetyltransferase; myeloperoxidase; polycyclic aromatic hydrocarbon, adult; allele; article; arylamine acetyltransferase gene; comet assay; DNA adduct; DNA determination; environmental exposure; ERCC5 gene; excision repair; female; gene; genetic polymorphism; genetic risk; genetic variability; genotype; human; Iran; methylenetetrahydrofolate reductase gene; myeloperoxidase gene; phenotype; priority journal; single nucleotide polymorphism, Adult; Alleles; Cohort Studies; DNA Adducts; DNA Repair; Female; Genotype; Humans; Iran; Middle Aged; Phenotype; Polycyclic Hydrocarbons, Aromatic; Polymorphism, Single Nucleotide
Subjects: مقالات نمایه شده محققین دانشگاه در سایت ,Web of Science ,Scopus
موارد کلی
Divisions: معاونت تحقیقات و فناوری
Depositing User: GOUMS
Date Deposited: 19 Apr 2015 09:35
Last Modified: 15 Jun 2015 05:44
URI: http://eprints.goums.ac.ir/id/eprint/2548

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