Genotypes and haplotypes of ERCC1 and ERCC2/XPD genes predict levels of benzo[a]pyrene diol epoxide-induced DNA adducts in cultured primary lymphocytes from healthy individuals: a genotype-phenotype correlation analysis
Open Access
- 1 July 2008
- journal article
- research article
- Published by Oxford University Press (OUP) in Carcinogenesis: Integrative Cancer Research
- Vol. 29 (8), 1560-1566
- https://doi.org/10.1093/carcin/bgn089
Abstract
Benzo[ a ]pyrene diol epoxide (BPDE)-induced DNA adducts are a risk factor for tobacco-related cancers. Excision repair cross-complementing complementation group 1 (ERCC1) and excision repair cross-complementing complementation group 2/xeroderma pigmentosum D (ERCC2/XPD) participate in the nucleotide excision repair (NER) pathway that removes BPDE–DNA adducts; however, few studies have provided population-based evidence for this association. Therefore, we assayed for levels of in vitro BPDE-induced DNA adducts and genotypes of single-nucleotide polymorphisms (SNPs) of the NER genes ERCC1 (rs3212986 and rs11615) and ERCC2/XPD (rs13181, rs1799793 and rs238406) in 707 healthy non-Hispanic whites. The linear trend test of increased adduct values in never to former to current smokers was statistically significant ( Ptrend = 0.0107). The median DNA adduct levels for the ERCC2 rs1799793 GG, GA and AA genotypes were 23, 29 and 30, respectively ( Ptrend = 0.057), but this trend was not observed for other SNPs. After adjustment for covariates, adduct values larger than the median value were significantly associated with the genotypes ERCC1 rs3212986TT [odds ratio (OR) = 1.89, 95% confidence interval (CI) = 1.03–3.48] and ERCC2/XPD rs238406AA (OR = 0.64, 95% CI = 0.41–0.99) and rs238406CA (OR = 0.63, 95% CI = 0.45–0.89) compared with their corresponding wild-type homozygous genotypes. The results of haplotype analysis further suggested that haplotypes CAC and CGA of ERCC2/XPD , TC of ERCC1 and CACTC of ERCC2/XPD and ERCC1 were significantly associated with high levels of DNA adducts compared with their most common haplotypes. Our findings suggest that the genotypes and haplotypes of ERCC1 and ERCC2/XPD may have an effect on in vitro BPDE-induced DNA adduct levels.Keywords
This publication has 36 references indexed in Scilit:
- Polymorphisms in Nucleotide Excision Repair Genes, Polycyclic Aromatic Hydrocarbon-DNA Adducts, and Breast Cancer RiskCancer Epidemiology, Biomarkers & Prevention, 2007
- Haplotype Analysis of theHSD17B1Gene and Risk of Breast Cancer: A Comprehensive Approach to Multicenter Analyses of Prospective Cohort StudiesCancer Research, 2006
- Nucleotide Excision RepairProgress in Nucleic Acid Research and Molecular Biology, 2005
- Polymorphism in the nuclear excision repair geneERCC2/XPD: association between an exon 6-exon 10 haplotype and susceptibility to cutaneous basal cell carcinomaHuman Mutation, 2005
- Nucleotide excision repair as a marker for susceptibility to tobacco-related cancers: A review of molecular epidemiological studiesMolecular Carcinogenesis, 2005
- DNA Repair Capacity of Lymphoblastoid Cell Lines From Sisters Discordant for Breast CancerJNCI Journal of the National Cancer Institute, 2005
- Deficient Nucleotide Excision Repair Capacity Enhances Human Prostate Cancer RiskCancer Research, 2004
- A Comparison of Bayesian Methods for Haplotype Reconstruction from Population Genotype DataAmerican Journal of Human Genetics, 2003
- Molecular epidemiology studies of carcinogenic environmental pollutantsMutation Research, 2003
- Sequential Assembly of the Nucleotide Excision Repair Factors In VivoMolecular Cell, 2001