Li R X, Shang J H, Sun J F
Department of Gastrointestinal Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Zhonghua Yi Xue Za Zhi. 2021 Mar 23;101(11):759-765. doi: 10.3760/cma.j.cn112137-20200708-02061.
To investigate the influence of X-ray repair cross complementing 1 (XRCC1) gene polymorphism on the prognosis and safety of stage Ⅲ patients with colorectal cancer (CRC) who received oxaliplatin based adjuvant chemotherapy. A total of 218 stage Ⅲ patients 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 with χ test. 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 (=0.905). GA and AA genotypes were merged in the subsequent analysis. The median DFS [ (95%)] 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 (χ²=6.943, =0.008). Furthermore, the median OS [ (95%)] of the two genotypes were 6.0 (5.3-6.7) years and 4.5 (3.9-5.1) years, which was statistically significant (χ²=5.538, =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) (=6.140, <0.001). 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.
探讨X射线修复交叉互补基因1(XRCC1)基因多态性对接受奥沙利铂辅助化疗的Ⅲ期结直肠癌(CRC)患者预后及安全性的影响。纳入2012年3月至2019年12月在郑州大学第一附属医院胃肠外科行R0切除并接受奥沙利铂辅助化疗的218例Ⅲ期CRC患者,收集其基线特征。其中男性125例,女性93例,年龄18~78岁。分别保存结直肠癌患者的外周血及外周血单个核细胞(PBMC)标本,用于XRCC1基因遗传变异的基因分型及XRCC1的mRNA表达检测。采用Kaplan-Meier生存分析方法分析基因型状态与预后的关系,采用χ检验分析基因型状态与不良反应的相关性。中位随访时间为4.9(0.3~7.3)年。218例CRC患者的中位无病生存期(DFS)为4.4年,中位总生存期(OS)为5.5年。218例患者中XRCC1基因rs1799782的基因型分布为:GG基因型62.4%(136/218),GA基因型33.0%(72/218),AA基因型4.6%(10/218),次要等位基因频率为0.21。三种基因型的分布频率符合Hardy-Weinberg平衡(P=0.905)。后续分析中将GA和AA基因型合并。GG基因型和GA/AA基因型的中位DFS[(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(χ²=6.943,P=0.008)。此外,两种基因型的中位OS[(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(χ²=5.538,P=0.010)。GA/AA基因型患者PBMC中XRCC1的mRNA表达为3.8±0.6,显著高于GG基因型患者(2.8±0.7)(t=6.140,P<0.001)。接受奥沙利铂辅助化疗的CRC患者的预后可能受XRCC1 rs1799782影响,其机制可能是通过介导XRCC1的mRNA表达来实现的。