[The influence of XRCC1 gene polymorphism on the prognosis and safety of stage â ¢ patients with colorectal cancer who received oxaliplatin based adjuvant chemotherapy].

ABSTRACT

Objective: 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. Methods: 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 χ2 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 (χ²=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 (χ²=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.