X线修复交叉互补基因1多态性对FOLFOX4方案治疗转移性结直肠癌疗效及毒副作用的影响

Effects of XRCC1 gene polymorphisms on efficacy and toxicity of FOLFOX4 chemotherapy for metastati ccolorectal cancer

目的探索X线修复交叉互补基因(XRCC1)多态性与奥沙利铂联合氟尿嘧啶和亚叶酸钙(FOLFOX4)方案治疗转移性结直肠癌有效率及毒副反应的关系。方法利用聚合酶链反应-连接酶检测反应(PCR-LDR)等方法对159例转移性结直肠癌患者进行XRCC1基因多态性检测。所有研究对象均接受4个周期以上的FOLFOX4方案化疗,满4个周期后全面评价疗效和毒副反应。结果159例转移性结直肠癌患者中,携带XRCC1 G/G、G/A和A/A基因型患者所占比例分别为52.2%、40.3%和7.6%;携带XRCC1 G/G型患者和携带G/A或A/A基因型患者的治疗有效率分别为60.2%和34.2%,2组之间差异有统计学意义(P<0.01);XRCC1 G/G基因型携带者的临床受益率明显高于G/A或A/A型携带者(P<0.01);XRCC1 G/G基因型患者恶心、呕吐的发生率明显低于G/A或A/A型患者(P<0.01),其余毒副反应各基因型患者之间差异无统计学意义(P>0.05)。结论转移性结直肠癌患者XRCC1基因多态性与FOLFOX4治疗方案疗效及毒副反应具有相关性。

Objective To study the effects of XRCC1 gene polymorphisms on efficacy and toxicity of FOLFOX4 protocol for metastatic eolorectal cancer （MCC）. Methods Polymerase chain reaction-ligation detection reaction （PCR-LDR） was employed to detect the XRCC1 gene polymorphisms in 159 patients with MCC who were treated with FOLFOX4 chemotherapy protocol for 4 weeks or more. This entailed comprehensive evaluation of the effi- cacy and toxicity following cessation of treatment. Results Of 159 cases with MCC, the frequencies of XRCC1 G/G, G/A and A/A genotypes were 52.2%, 40.3% and 7.6%, respectively. The responsive rates to therapy were 60.2% and 34.2% in patients with XRCC1 G/G genotype and G/A or A/A genotype, respectively （P〈0.01）. Carriers of XRCC1 G/G genotype had a remarkably higher clinical beneficial rate （CR＋PR＋SD） than carriers of G/A or A/A genotype （both P〈0.01）. Compared with G/A or A/A genotype carriers, the incidence of nausea and vomiting was significantly lower in XRCC1 G/G genotype carriers （P〈0.01）. The difference in toxicity among remaining types of carriers was un- remarkable （P〉0.05）. Conclusion XRCC1 gene polymorphisms are associated with the efficacy and toxicity of FOL- FOX4 chemotherapy for MCC.