Correlation Between DNA Damage Repair Gene Polymorphism And Prognosis Of Non-small Cell Lung Cancer

Among malignant tumors,lung cancer has the highest incidence and mortality.Nonsmall cell lung cancer accounts for 80.2-85.0% of lung cancer.Compared with small cell lung cancer,non-small cell lung cancer has slower cell growth and division,and the spread and metastasis are relatively late.Therefore,patients with non-small cell lung cancer are mostly advanced and often lose their chance of surgery.In the past 20 years,the treatment of lung cancer has undergone major changes,and targeted therapy and tumor immunotherapy have achieved good results in some patients.The driving gene mutations targeted by targeted therapy mainly include EGFR mutation,ALK gene fusion and ROS1 gene rearrangement.The results of the survey showed that the incidence of EGFR mutations in non-small cell lung cancer patients ranged from 9% to 27%,the incidence of ALK gene fusion was less than 8%,and the incidence of ROS1 gene rearrangement was below 2%.Therapy is more suitable for patients with high expression of the PD-L1 gene.Platinum-based two-drug combination chemotherapy is still the standard means of treating non-small cell lung cancer.Platinum drugs as non-small cell lung cancer chemotherapy drugs,the mechanism of action is that platinum drugs and DNA form intrachain or interchain cross-linking reaction,blocking DNA replication,mitotic stagnation.The adduct formed by the platinum drug and the DNA,after being recognized by the body cells,initiates a repair mechanism to delay or avoid apoptosis of the tumor cells.The polymorphisms associated with DNA repair systems may affect the DNA damage repair function,which in turn affects the DNA damage repair process caused by platinum drugs.Therefore,DNA damage repair gene polymorphism may be associated with the prognosis of platinumbased chemotherapy.Nucleotide excision repair and base excision repair are two important ways in which platinum-based drugs repair DNA after injury.This study included samples from the First People's Hospital of Yunnan Province receiving platinumbased chemotherapy for patients with advanced non-small cell lung cancer,collecting peripheral blood from patients according to the principle of informed consent,extracting DNA by phenol-chloroform method,and nucleosides of 116 patients by SNapShot technique.The 15 SNP loci of the acid excision repair pathway-related genes(ERCC1,ERCC2,ERCC3,ERCC4,ERCC5)and the base excision repair pathway-related genes(XRCC1,XRCC2)were genotyped.This study aims to explore the relationship between polymorphisms related to DNA damage repair system and the prognosis of platinumbased chemotherapy,and provide a theoretical basis for personalized treatment of patients with non-small cell lung cancer.Kaplan-Meier survival curve evaluation showed that the median Progression-free survival of XRCC1 gene rs25489(G>A)wild-type genotype GG was 12.00 months,and the median Progression-free survival time with mutant allele A was present.For 4.20 months,it was shown that wild type had a better prognosis for platinum-based chemotherapy(rs25489 GA+AA vs GG: P=0.009;HR=3.17;95% CI: 1.36-7.09).XRCC1 gene rs1799782(C>T)The median Progression-free survival of wild-type genotype CC was 5.60 months,and the median Progression-free survival with the mutant allele T was 12.90 months.The genotype had a better prognosis for platinum-based chemotherapy(rs1799782 TT+CT vs CC: P=0.048;HR=0.91;95% CI: 0.81-0.99).COX risk proportional regression model adjusted covariates(sickness of disease diagnosis,past disease history,history of smoking,smoking index size,clinical stage,presence or absence of visceral metastasis),XRCC1 gene rs25489(G>A)and rs1799782(C>T There was a statistically significant difference in the median progression-free survival between the wild type and the mutant genotypes(rs25489 GA+AA vs GG: Adjust P=0.045;HR=1.08;95% CI: 0.84-1.39.rs1799782 TT+CT vs CC: Adjust P = 0.040;HR = 0.88;95% CI: 0.78-0.99).Further subgroup analysis: XRCC1 gene rs25489 site in the younger than 65 years old patients with wild-type genotype GG median Progression-free survival of 12.00 months,carrying a mutation-type allele A median Progression-free progression The survival time was 4.20 months,indicating that the wild type is more sensitive to platinumbased chemotherapy and has a better prognosis(rs25489 GA+AA vs GG: P=0.046;HR=2.07;95% CI: 1.03-4.15).The median Progression-free survival of the wild-type genotype GG of the XRCC1 gene rs25489 in the history of smoking was 12.00 months,and the median progression-free survival of the mutant allele A was 5.00 months.The results indicated that the wild-type genotype had a better prognosis for platinum-based chemotherapy(rs25489 GA+AA vs GG: P=0.027;HR=2.37;95% CI: 1.63-3.25).The median Progression-free survival of the wild type genotype GG of the XRCC1 gene rs25489 was 12.00 months in the clinical stage IV patients,and the median Progressionfree survival with the mutant allele A was 5.00 months.The results indicated that the wildtype genotype had a better prognosis for platinum-based chemotherapy(rs25489 GA+AA vs GG: P=0.016;HR=2.30;95% CI: 1.05-5.05).The median Progression-free survival of the wild-type genotype CC in the stage IV patients with XRCC1 gene rs1799782 was 5.60 months,and the median progression-free survival with the mutant allele T was 12.90 months.The results indicated that the mutant genotype had a better prognosis for platinum-based chemotherapy(rs1799782 TT+CT vs CC: P=0.031;HR=0.87;95% CI: 0.76-0.98).In summary,the DNA repair system BER pathway XRCC1 gene polymorphism rs25489 and rs1799782 is associated with chemotherapy prognosis.The XRCC1 gene rs25489 wild-type genotype GG has a better prognosis for platinum in the treatment of advanced non-small cell lung cancer.Patients with non-small cell lung cancer who carry the allele T at the rs1799782 of the XRCC1 gene have a better prognosis for chemotherapy and benefit from platinum-based chemotherapy.