The Correlation Study Between SNPs Of MTHFD1、MTR、MTRR、XRCC1 Gene And Efficacy Of Pemetrexed Combind Platinum Chemotherapy In Lung Adenocarcinoma

Background and Obiective:Lung cancer is currently the leading cause of cancer-related deaths in both men and women worldwide.Non-small cell lung cancer(NSCLC)accounts for about 85%of all lung cancer types,and about 40%of the pathological types are adenocarcinomas.The treatment options for advanced lung cancer are limited,and advanced NCSLC without a driver gene is still dominated by systemic chemotherapy.The combination of pemetrexed with cisplatin(PP)is currently one of the first choices for the treatment of advanced lung adenocarcinoma.However,it has been clinically discovered that a large proportion of patients have the same histopathology and clinical stage,but the efficiency of chemotherapy and the prognosis exist.Significant differences.Studies have shown that this difference is associated with single nucleotide polymorphisms(SNPs)associated with pemetre xed-targe t folate-metabolizing enzyme genes and platinum-targeted genes,and SNPs respond well to individuals.Differences from the crowd.Currently,there are methionine synthase gene(MTR),methionine synthetase reductase(MTRR),methylenetetrahydrofolate dehydrogenase 1(MTHFD1)and DNA repair gene X-ray interlaced complementary There are few studies on the efficacy and prognosis of advanced lung adenocarcinoma chemotherapy with first-line SNP and PP regimens of the repair gene(XRCC1).This study investigated the SNPs of the folic acid metabolic enzyme genes MTR rs3768160,MTRR rs2966952/rs 1532268,MTHFD1 rs2236225/rs 1950902,and XRCC1 rs25487/rs 1799782 to investigate the efficacy of first-line SNP of each locus and late-stage lung adenocarcinoma in the treatment of first-line chemotherapy with PP.The relationship between disease control rate and progression-free survival time(PFS),finding relevant beneficial indicators,expecting to be able to better select the dominant population of chemotherapy for PP regimens,and truly achieving accurate individualized chemotherapy for patients with advanced lung adenocarcinoma.Methods:The blood samples of 60 patients with advanced lung adenocarcinoma who underwent first-line chemotherapy of the PP protocol for the first time in the Department of Oncology in the First Affiliated Hospital of Dalian Medical University from January 2016 to January 2017 were collected and followed up to January 2018.The SNPs of each gene locus were detected by Snapshot sequencing and all data were statistically analyzed using SPSS19.0 software.The correlations between clinicopathological characteristics and chemotherapy efficacy and disease control law were tested using X2 test or Fish’s exact test;genotype and chemotherapy The relation between the efficiency and the disease control law was analyzed by disordered multi-class Logistic regression analysis.The relationship between genotype and PFS was analyzed by log-rank.The survival curve was plotted by kaplan-meier method and COX regression analysis was performed.P<0.05 was used as the difference.Statistically significant.Result:1.The frequencies of MTR rs3768160,MTRR is2966952/rs532268,MTHFD1 rs2236225/rs 1950902 and XRCC1 rs25487/rs 1799782 gene loci were all consistent with Hardy-Weinberg genetic balance(P>0.05).2.The effective rates of chemotherapy for patients with GG,GA,and AA genotypes in MTRR rs2966952 were 42.3%,20.8%,and 10.0%,respectively;for wild-type GG,the effective rate of GA+AA genotypes was 17.6%.Chemotherapy was performed in GG patients.The effective rate was higher than that of patients with GA+AA type(P=0.040).After adjusting for age,gender,and degree of differentiation by multivariate regression analysis,the GA+AA genotype chemotherapy response rate was 0.251 times that of GG type(P=0.028).Chemotherapy with patients with A alleles is less effective than non-carriers.3.Median PFS(7.0 months)in patients with GG+GA genotype in MTRR rs2966952 was longer than median PFS in patients with AA(4.0 months)(P=0.015);after adjusting for age,gender,and degree of differentiation,GG+GA type There was no significant difference in the median PFS between patients and AA patients(P=0.079).4.Median PFS(7.0 months)in patients with GG genotype in XRCC1 rs25487 was longer than median PFS in patients with GA+AA(3.0 months)(P = 0.013).After adjusting for age,sex,and differentiation,the risk of progression in patients with XRCC1 rs25487 GA+AA was 1.405 times higher than in patients with GG(P=0.033),ie,patients with the A allele were more likely to have progress.5.The SNPs of MTR rs3768160,MTRR rs532268,MTHFD1 rs2236225/rs 1950902,and XRCC1 rs 1799782 may not be significantly associated with chemotherapy efficiency,disease control rate,and PFS(P>0.05).Conclusion:1.The MTRR rs2966952 gene polymorphism may be related to the efficiency of chemotherapy,and patients with A allele have low chemosensitivity;2.The MTRR rs2966952 gene polymorphism may be an independent factor of PFS,and patients carrying the A allele may progress faster;3.XRCC1 rs25487 polymorphism may be an independent factor for PFS,and patients carrying the A allele may progress faster;4.The polymorphisms of MTR rs3768160,MTRR rs532268,MTHFD1 rs2236225/rs 1950902 and XRCC1 rs 1799782 may not be significantly associated with chemotherapy efficacy,disease control rate and PFS.