XRCC1基因多态性对接受奥沙利铂为基础辅助化疗的Ⅲ期结直肠癌患者预后及安全性的影响

The influence of XRCC1 gene polymorphism on the prognosis and safety of stage Ⅲ patients with colorectal cancer who received oxaliplatin based adjuvant chemotherapy

目的探讨X射线修复交叉互补1(XRCC1)基因多态性对接受奥沙利铂为基础辅助化疗的Ⅲ期结直肠癌患者预后及安全性的影响。方法回顾性分析2012年3月至2019年12月郑州大学第一附属医院胃肠外科218例R0切除术后接受奥沙利铂为基础辅助化疗的Ⅲ期结直肠癌患者的临床资料。其中男125例,女93例,年龄18~78岁。留取患者的外周血及外周血单核细胞(PBMC)分别用来进行XRCC1多态性基因分型及XRCC1基因的mRNA表达分析。通过Kaplan-Meier生存分析方法分析基因型和预后的相关性,通过χ^(2)检验分析方法探讨基因型和不良反应的相关性。结果218例结直肠癌患者的中位随访时间为4.9(0.3~7.3)年,中位无疾病生存期(DFS)为4.4年,中位总生存期(OS)为5.5年。XRCC1基因rs1799782位点的分布频率为:GG基因型占62.4%(136/218),GA型占33.0%(72/218),AA型占4.6%(10/218),最小等位基因频率为0.21,3种基因型分布频率符合哈迪温伯格平衡(P=0.905)。后续的分析将GA和AA型患者合并,GG基因型和GA/AA基因型患者的DFS[M(95%CI)]分别为5.2(4.5~5.9)年和3.8(3.2~4.4)年,差异有统计学意义(χ^(2)=6.943,P=0.008)。两种基因型患者的OS[M(95%CI)]分别为6.0(5.3~6.7)年和4.5(3.9~5.1)年,差异有统计学意义(χ^(2)=5.538,P=0.010)。GA/AA基因型患者的PBMC中XRCC1基因mRNA的表达水平为3.8±0.6,高于GG型患者的2.8±0.7,差异有统计学意义(t=6.140,P<0.001)。结论XRCC1基因rs1799782位点可能通过介导XRCC1基因mRNA的表达,从而影响接受奥沙利铂为基础辅助化疗的结直肠癌患者的预后。

Objective To investigate the influence of X-ray repair cross complementing 1(XRCC1)gene polymorphism on the prognosis and safety of stageⅢpatients with colorectal cancer(CRC)who received oxaliplatin based adjuvant chemotherapy.Methods A total of 218 stageⅢpatients with CRC after R0 resection and received oxaliplatin based adjuvant chemotherapy in the department of gastrointestinal surgery of the First Affiliated Hospital of Zhengzhou University from March 2012 to December 2019 were included and the baseline characteristics were collected.There were 125 male and 93 female patients,aged from 18 to 78 years.Peripheral blood and peripheral blood mononuclear cell(PBMC)specimens of the colorectal cancer patients were preserved for genotyping of XRCC1 gene genetic variation and mRNA expression of XRCC1,respectively.The association between genotype status and prognosis was analyzed by Kaplan-Meier survival analysis.And the correlation between genotype status and adverse reactions was performed withχ^(2) test.Results The median follow-up time were 4.9(0.3-7.3)years.The median disease-free survival(DFS)of the 218 patients with CRC was 4.4 years and the median overall survival(OS)was 5.5 years.The prevalence of rs1799782 in XRCC1 gene among the 218 patients was:GG genotype 62.4%(136/218),GA genotype 33.0%(72/218)and AA genotype 4.6%(10/218),minor allele frequency was 0.21.And the distribution frequencies of the three genotypes were in accordance with the hardy-weinberg equilibrium(P=0.905).GA and AA genotypes were merged in the subsequent analysis.The median DFS[M(95%CI)]of GG genotype and GA/AA genotype was 5.2(4.5-5.9)years and 3.8(3.2-4.4)years,which was statistically significant(χ^(2)=6.943,P=0.008).Furthermore,the median OS[M(95%CI)]of the two genotypes were 6.0(5.3-6.7)years and 4.5(3.9-5.1)years,which was statistically significant(χ^(2)=5.538,P=0.010).The mRNA expression of XRCC1 in PBMC of the patients with GA/AA genotypes was 3.8±0.6,which was significantly higher than that of the GG genotype patients(2.8±0.7)(t=6.140,P<0.001).Conclusion The prognosis of patients with CRC who received oxaliplatin based adjuvant chemotherapy may be influenced by XRCC1 rs1799782 through mediating the mRNA expression of XRCC1.