碱基切除修复基因多态性与晚期非小细胞肺癌铂类药物化疗敏感性

目的：探讨DNA碱基切除修复通路中XRCC1 Arg399Gln和ADPRT Val762Ala基因多态性与晚期非小细胞肺癌（NSCLC）铂类药物化疗敏感性的关联，并与先前报道的XRCC1 T-77C、Argl94Trp联合分析其预测作用。方法：收集接受铂类药物为基础化疗的晚期NSCLC患者107例，用PCR—RFLP法检测基因型，分析各基因型与铂类药物化疗有效率的关联，并以非条件Logistic回归模型对患者年龄、性别、病理类型、临床分期和治疗方案进行校正。结果：对XRCC1 Arg399Gln多态性进行单因素分析时，发现携带至少1个Gln等位基因的患者的化疗有效率是携带Arg／Arg基因型者的0．42倍（95％CI：0．19—0．93），差异具有统计学意义；经多因素校正后发现携带至少1个Gln等位基因的患者的化疗有效率是携带Arg／Arg基因型者的0．52倍（95％CI：0．22—1．26），但差异不再具有统计学意义。对ADPRT Val762Ala多态性进行多因素分析时，发现携带至少1个Ala等位基因的患者的化疗有效率是携带Val／Val基因型者的1．57倍（95％CI：0．67—3．66）。联合分析各患者4个多态性位点的铂类药物敏感基因型的总数目与铂类药物化疗有效率的关联，并经多因素分析校正后，发现携带3—4个铂类药物敏感基因型的患者的化疗有效率是具有0—2个铂类药物敏感基因型者的4．15倍（95％CI：1．54—11．19），差异具有统计学意义。结论：XRCC1 Arg399Gln多态性与铂类药物化疗敏感性的关系需进一步确认，似乎携带野生型Arg／Arg者对铂类药物化疗更敏感；但未能发现ADPRT Val762Ala多态性与锥苑矧别眇德魄牲存在明显关联；4个多态性位点联合分析的预测效能高于单个位点。

Predictive value of base -excision repair gene polymorphisms in advanced non -small cell lung cancer patients receiving platinum -based chemotherapy

Objective：To investigate the association between XRCC1 Arg399Gln and ADPRT Va1762Ala polymorphisms and chemotherapy sensitivity in advanced non - small cell lung cancer patients receiving platinum - based chemotherapy,and also analyze the combined predictive effect with the previous reported XRCCI T- 77C ,Arg194Trp polymorphisms. Methods： A total of 107 advanced lung cancer patients receiving platinum - based chemotherapy were involved. Genotypes were detected by PCR - RFLP method. The association between genotype and response rate was evaluated. Logistic regression was used to adjust for sex, year, pathological type, clinical stage, and therapeutic regimen. Results：For XRCC1 Arg399Gln polymorphism, XRCC1 399 Gin carriers had a lower response rate than the wild genotype carriers （ crude OR = 0.42,95 % CI ： 0.19 - 0.93 ; adjusted OR = 0.52,95 % CI：0.22 - 1.26）. For ADPRT Va1762Ala polymorphism,ADPRT 762Ala carriers had a higher response rate than the wild genotype carriers （adjusted OR = 1.57,95% CI：0.67 -3.66）. Compared with the carriers with sensitive alleles to platinum - based chemotherapy less than three,the carriers with three or four drug sensitive alleles were more sensitive to platinum - based chemotherapy （ adjusted OR = 4.51,95% CI ： 1.54 - 11.19 ）. Conclusion： The predictive value of XRCC1 Arg399Gln polymorphism needed further confirmation, it seemed that the Arg/Arg carriers were more sensitive to platinum - based chemotherapy. However, no association was found for ADPRT Va1762Ala polymorphism and response rate. The combined predictive values of four polymorphisms may be more powerful than single one.