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 8 DNA repair genes. NER capacity was evaluated by a modified comet assay, and aromatic DNA adduct levels were measured in blood by (32) P-postlabelling. 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 3-4 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. (c) 2012 Wiley Periodicals, Inc.
Original language | English |
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Pages (from-to) | 2738-2747 |
Number of pages | 10 |
Journal | International Journal of Cancer |
Volume | 132 |
Issue number | 12 |
DOIs | |
Publication status | Published - 15 Jun 2013 |
Keywords
- polycyclic aromatic hydrocarbons
- DNA adducts
- nucleotide excision repair
- polymorphism
- POLYCYCLIC AROMATIC-HYDROCARBONS
- 1-HYDROXYPYRENE GLUCURONIDE CONCENTRATIONS
- PULMONARY EPITHELIAL-CELLS
- GRANDE-DO-SUL
- ESOPHAGEAL CANCER
- HEALTHY-SUBJECTS
- HIGH-RISK
- EXPOSURE
- GSTM1
- LUNG