Variation in PAH‐related DNA adduct levels among non‐smokers: The role of multiple genetic polymorphisms and nucleotide excision repair phenotype. Issue 12 (17th December 2012)

• Record Type: Journal Article
• 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.
• Is Part Of: International journal of cancer. Volume 132:Issue 12(2013:Jun. 15)
• Page Start: 2738
• Page End: 2747
• Publication Date: 2012-12-17
• Subjects: Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.27953
• Languages: English
• ISSNs: 0020-7136

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>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 by<xref ref-type="link" rid="bib32">32</xref>P‐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<sup>8</sup> nucleotides (mean: 5.8 ± 3.1). DNA adduct level was significantly lower in homozygotes for <italic>NAT2</italic> slow alleles and <italic>ERCC5</italic> non‐risk‐allele genotype, and was higher in the <italic>MPO</italic> homozygote risk‐allele genotype. The sum of risk alleles in these genes significantly correlated with the log‐adduct level (<italic>r</italic> = 0.4, <italic>p</italic> < 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 <italic>MTHFR</italic> and <italic>ERCC1</italic> 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.</p> </abstract>