ERCC2/XPD单核苷酸多态与苯并芘体外诱导DNA加合物损伤的关联性研究

目的评价环境致癌因子苯并芘(Ba]P)所致DNA损伤修复与ERCC2/XPD单核苷酸多态(SNP)的关联。方法收集282例辽宁地区汉族健康人群外周血8ml,常规提取淋巴细胞及DNA,采用Taqman实时定量PCR检测ERCC2/XPDLys751Gln(rs13181),Asp312Asn(rs1799793)和Arg156Arg(rs238406)的基因型;体外培养淋巴细胞,应用Ba]P及S9活化系统,诱导BPDE-DNA加合物的形成;高效液相色谱法检测BPDE-DNA加合物含量;分析BPDE-DNA加合物水平与ERCC2/XPD SNP位点的关联。结果携带ERCC2/XPD Arg156Arg位点AA基因型个体BPDE-DNA加合物水平显著高于CC基因型携带者;50～70岁和≥70岁年龄组人群的加合物水平高于≤30岁年龄组(P<0.05);多元线性回归分析同样显示,ERCC2/XPD Arg156Arg位点SNP及年龄对BPDE-DNA加合物含量的影响有统计学意义(P<0.05)。结论 ERCC2/XPD Arg156Arg位点A等位基因可能与BPDE-DNA加合物的DNA修复能力降低相关联,可能会增加肿瘤易感风险。

Study on association between ERCC2/XPD single nucleotide polymorphisms and DNA adducts damage induced by B [a] P in vitro

Objective To evaluate the association between DNA damage repair capacity induced by environment carcinogen benzoa]pyrene(Ba]P) and ERCC2/XPD single nucleotide polymorphisms(SNP).Methods 8ml peripheral bloods of 282 healthy ethnic Han people from Liao-ning province were collected,isolated lymphocytes and extracted DNA.The genotypes of ERCC2/XPD Lys751Gln(rs13181),Asp312Asn(rs1799793),Arg156Arg(rs238406) were detected by Taqman real time PCR;BPDE-DNA adduct in vitro induced by Ba]P and S9 mixture in lymphocyte were detected by high performance liquid chromatography(HPLC).Results The BPDE-DNA adduct levels of ERCC2/XPD Arg156Arg AA genotype were significantly higher than CC genotype.Compared with ≤30 years,people at age of 50-70years and ≥70 years have higher BPDE-DNA adduct level(P<0.05).Multiple covariates analysis showed SNP of ERCC2/XPD Arg156Arg(rs238406) and age have been related to BPDE-DNA adduct levels closely among all covariates(P<0.05).Conclusion ERCC2/XPD Arg156Arg rs238406 polymorphisms may be associated with DNA repair capacity in excising BPDE-DNA adduct and A allele may increase the risks of cancer susceptibility.