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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 ofin vitroBPDE-induced DNA adducts and genotypes of single-nucleotide polymorphisms (SNPs) of the NER genesERCC1(rs3212986 and rs11615) andERCC2/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 (P  trend = 0.0107). The median DNA adduct levels for theERCC2rs1799793 GG, GA and AA genotypes were 23, 29 and 30, respectively (P  trend = 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 genotypesERCC1rs3212986TT [odds ratio (OR) = 1.89, 95% confidence interval (CI) = 1.03–3.48] andERCC2/XPDrs238406AA (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 ofERCC2/XPD, TC ofERCC1and CACTC ofERCC2/XPDandERCC1were significantly associated with high levels of DNA adducts compared with their most common haplotypes. Our findings suggest that the genotypes and haplotypes ofERCC1andERCC2/XPDmay have an effect onin vitroBPDE-induced DNA adduct levels.

carcinogenesis

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