Variation in PAH-related DNA adduct levels among non-smokers: The role of multiple genetic polymorphisms and nucleotide excision repair phenotype.
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Authors
Etemadi, ArashIslami, Farhad
Phillips, David H.
Godschalk, Roger
Golozar, Asieh
Kamangar, Farin
Malekshah, Akbar Fazel-Tabar
Pourshams, Akram
Elahi, Seerat
Ghojaghi, Farhad
Strickland, Paul T.
Taylor, Philip R.
Boffetta, Paolo
Abnet, Christian C.
Dawsey, Sanford M.
Malekzadeh, Reza
van Schooten, Frederik J.
Issue Date
2012-11-23
Metadata
Show full item recordAbstract
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 10(8) 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.Citation
Int. J. Cancer 2013, 132 (12):2738-2747PubMed ID
23175176Additional Links
http://onlinelibrary.wiley.com/doi/10.1002/ijc.27953/abstractType
ArticleLanguage
enISSN
1097-0215Sponsors
Grant sponsor: Environmental Cancer Risk, Nutrition and Individual Susceptibility (ECNIS), a network of excellence operating within the European Union 6th Framework Program [Priority 5: ‘‘Food Quality and Safety’’]; Grant number: 513943;ae974a485f413a2113503eed53cd6c53
10.1002/ijc.27953
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