Journal Article

Genotypes and haplotypes of <i>ERCC1</i> and <i>ERCC2/XPD</i> genes predict levels of benzo[<i>a</i>]pyrene diol epoxide-induced DNA adducts in cultured primary lymphocytes from healthy individuals: a genotype–phenotype correlation analysis

Hui Zhao, Li-E Wang, Donghui Li, Robert M. Chamberlain, Erich M. Sturgis and Qingyi Wei

in Carcinogenesis

Volume 29, issue 8, pages 1560-1566
Published in print August 2008 | ISSN: 0143-3334
Published online July 2008 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgn089
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

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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.

Journal Article.  5136 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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