The Study Ofchemo-radiotherapy Effect Of Lung Cancer Based On DNA Repair Gene SNPs

Lung cancer is the first in the incidence and mortality in China.At present,surgery,radiotherapy and chemotherapy is still the main treatment of lung cancer.But even the same pathological types and the same period of patients still have a huge difference of curative effect.The central mechanism of radiotherapy and chemotherapy in the treatment of cancer is caused by the DNA damage in the tumor cells,which leads to the irreversible death of the tumor cells.Therefore,it is important to understand the role of DNA repair pathway related genes in tumor radiotherapy and chemotherapy.Single nucleotide polymorphism(SNP)is the third generation of molecular markers of genetic variation,which is mainly used to study the differences in susceptibility of the disease and different agents and treatment methods.Up to now,there is no more comprehensive study of DNA repair genes and the sensitivity of radiotherapy and chemotherapy.This article will study the polymorphism of DNA repair related pathway gene,analyze the correlation of SNPs and radio-chemotherapy,and explore the difference of curative effect based on SNPs of DNA damage repair pathway genes.In this study,the data of patients with lung cancer were analyzed systematically,and the relationship between NSCLC and SCLC and various clinical factors were analyzed firstly.The single factor and multi clinical factor were analyzed on the 175 cases of non-small cell lung cancer(NSCLC)and 147 cases of small cell lung cancer(SCLC).The results proved that the sensitive of radio-chemotherapy are the key factors to determine the efficacy of radio-chemotherapy.Based on the support of clinical data,26 SNPs sites related with DNA damage repair genes were identified by using database screening and literature search.And using MassARRAY iPLEX Sequenom platform for SNP genotyping,26 SNPs loci were obtained from 260 patients with lung cancer in North China.And compared with China Han SNP genotype on HapMap,the results showed that the AA genotype of rs2736098 was significantly lower in the proportion of patients with lung cancer,and AG genotype was significantly increased rates of cancer.In the analysis of the relation between different pathological types and SNPs,rs25406(CT)in small cell carcinoma,rs2735343(GC),rs8073069(CG)and rs2853677(TT)in quamous cell carcinoma and rs2279744(GT),rs2228001(AA)and rs2736098(AG)were higher proportion.Rs1042858(GG)is related with the stage of adenocarcinoma,as so on the rs1801270(CA),rs2279744(GT)with squamous cell carcinoma stage,rs2736098(AG)and rs2132572(AA)with SCLC stage.This study focused on the relationship between DNA damage repair related genes SNPs and NSCLC on the sensitivity,efficacy and survival time,and found that some SNPs of DNA damage repair related genes affect the sensitivity of NSCLC.In squamous cell carcinoma,rs2228000,rs2228001(XPC),rs2273953(TP73),rs2279744(MDM2),rs2299939(PTEN),rs8178085 and rs12334811(DNA-PKcs)affect the sensitivity to chemotherapy.rs8178085 and rs12334811(DNA-PKcs)affect radiotherapy sensitivity.In adenocarcinoma,rs2699887(PI3K)and rs12334811(DNA-PKcs)affect the sensitivity to chemotherapy,and rs2299939 and rs2735343(PTEN)affect the sensitivity to radiotherapy.Further analysis revealed that these SNPs are mainly located in the PI3K/PTEN/AKT/mTOR signaling pathway,NHEJ repair pathway and P53 related pathway.The results of SNPs analysis showed a significant correlation with the survival time of rs2279744,rs1801270,rs2909430 and rs2273953 with NSCLC survival,rs2299939 locus associated with adenocarcinoma,rs12334811 locus associated with squamous cell carcinoma.At the same time,the combination of SNPs can significantly improve the median survival time.Patients with GG genotype of rs12334811 and CC genotype of rs2273953 can increase the median PFS from 14 months to 17 months.Rs2299939 loci with non AA genotype and rs2909430(AA),rs2279744(non GG)and s402710(CC)in patients with adenocarcinoma can increase the median PFS from 10 months to 14 months.In addition,through the eQTLs analysis,we found that rs2228001 and rs2228000 can regulate the XPC gene,rs344781 can regulate the PLAUR gene,rs8073069 can regulate the expression of BIRC5 gene.This suggests that the SNPs mutation may cause the change of the expression of genes related to DNA damage repair,which can affect the sensitivity of tumor cells to radiotherapy and chemotherapy,and the survival time of the patients.Based on the results of NSCLC,the research preliminary analyzes the relationship between SNPs and SCLC chemotherapy sensitivity,curative effect and survival time.The results suggests that there was a significant correlation between rs11516,rs25406,rs2132572,rs2735343,rs10937405 and recurrence time of SCLC more than 90 days as first-line treatment,patients with CC genotype of rs11615 and TT genotype of rs 10937405 can prolong the recurrence time.So SNPs could be used as biological indicators of the treatment and prognosis judgment.According to the relationship between SNPs and survival time of SCLC,in the age of patients,clinical stage unchanged conditions,rs11615,rs1042522,rs1801270,rs2132572,rs2279744,rs2299939 and rs10937405 have significant effects on SCLC progression free survival time.Patients with CC genotype of rs2299939 and CT genotype of rs11615 can significantly influence the median time of patients,increased from 11 months to 18 months.In this study,the clinical first-line data are used as the materials.The study analyzed the relation between efficacy of radiotherapy and chemotherapy and 26 SNPs loci of 260 cases of lung cancer,and systematic research the relationship of DNA damage repair related genes SNPs and efficacy of radiotherapy and chemotherapy.A large amount of data of the study will lay the foundation for the subsequent research on the radiotherapy and chemotherapy and DNA repair pathways,improve the pertinence of individualized chemoradiotherapy,and provide new ideas to improve the efficacy of radiochemotherapy.