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

2.50
Hdl Handle:
http://hdl.handle.net/10146/269639
Title:
Variation in PAH-related DNA adduct levels among non-smokers: The role of multiple genetic polymorphisms and nucleotide excision repair phenotype.
Authors:
Etemadi, Arash; Islami, 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.
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 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):2738-2747
Journal:
International Journal of Cancer. Journal international du cancer
Issue Date:
23-Nov-2012
URI:
http://hdl.handle.net/10146/269639
DOI:
10.1002/ijc.27953
PubMed ID:
23175176
Additional Links:
http://onlinelibrary.wiley.com/doi/10.1002/ijc.27953/abstract
Type:
Article
Language:
en
ISSN:
1097-0215
Sponsors:
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;
Appears in Collections:
Articles

Full metadata record

DC FieldValue Language
dc.contributor.authorEtemadi, Arashen_GB
dc.contributor.authorIslami, Farhaden_GB
dc.contributor.authorPhillips, David H.en_GB
dc.contributor.authorGodschalk, Rogeren_GB
dc.contributor.authorGolozar, Asiehen_GB
dc.contributor.authorKamangar, Farinen_GB
dc.contributor.authorMalekshah, Akbar Fazel-Tabaren_GB
dc.contributor.authorPourshams, Akramen_GB
dc.contributor.authorElahi, Seeraten_GB
dc.contributor.authorGhojaghi, Farhaden_GB
dc.contributor.authorStrickland, Paul T.en_GB
dc.contributor.authorTaylor, Philip R.en_GB
dc.contributor.authorBoffetta, Paoloen_GB
dc.contributor.authorAbnet, Christian C.en_GB
dc.contributor.authorDawsey, Sanford M.en_GB
dc.contributor.authorMalekzadeh, Rezaen_GB
dc.contributor.authorvan Schooten, Frederik J.en_GB
dc.date.accessioned2013-02-15T13:56:33Z-
dc.date.available2013-02-15T13:56:33Z-
dc.date.issued2012-11-23-
dc.identifier.citationInt. J. Cancer 2013, 132 (12):2738-2747en_GB
dc.identifier.issn1097-0215-
dc.identifier.pmid23175176-
dc.identifier.doi10.1002/ijc.27953-
dc.identifier.urihttp://hdl.handle.net/10146/269639-
dc.description.abstractPolycyclic 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.en_GB
dc.description.sponsorshipGrant 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;en_GB
dc.languageENG-
dc.language.isoenen
dc.relation.urlhttp://onlinelibrary.wiley.com/doi/10.1002/ijc.27953/abstracten_GB
dc.rightsArchived with thanks to International journal of cancer. Journal international du canceren_GB
dc.subjectPolycyclic aromatic hydrocarbonsen_GB
dc.subjectDNA adductsen_GB
dc.subjectPolymorphismen_GB
dc.subjectNucleotide excision repairen_GB
dc.subject.meshAdult-
dc.subject.meshAlleles-
dc.subject.meshCohort Studies-
dc.subject.meshDNA Adducts-
dc.subject.meshDNA Repair-
dc.subject.meshFemale-
dc.subject.meshGenotype-
dc.subject.meshHumans-
dc.subject.meshIran-
dc.subject.meshMiddle Aged-
dc.subject.meshPhenotype-
dc.subject.meshPolycyclic Hydrocarbons, Aromatic-
dc.subject.meshPolymorphism, Single Nucleotide-
dc.titleVariation in PAH-related DNA adduct levels among non-smokers: The role of multiple genetic polymorphisms and nucleotide excision repair phenotype.en
dc.typeArticleen
dc.identifier.journalInternational Journal of Cancer. Journal international du canceren_GB

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