Neil2 Gene Rs8191670 Polymorphism(T/C) Is Associated With Chemotherapy Sensitivity Of Non-Small Cell Lung Cancer

BackgroundLung cancer,with the highest morbidity and mortality in the world today,has become a major public health problem worldwide.In our country,lung cancer is the most common malignant tumor in men,and the second most common malignant tumor in females,just next to breast cancer.At present,the incidence and death rate of lung cancer in China has been developing rapidly,and the incidence of the disease has increased nearly five times in the last 30 years.It is the first cause of leading to death in the urban population.About 600,000 people in China have died of lung cancer every year.Cisplatin-based combination chemotherapy is the first line of treatment for advanced non-small cell lung cancer.While,the response rate of patients to chemotherapy was different,which differs from 26% to 60%.A variety of factors affect the efficacy of chemotherapy for the tumor,including the tumor cells' tolerance to chemotherapeutic drugs,the metabolic level of chemotherapy drugs in the body,and the changes of DNA repair capacity.The gene polymorphisms of DNA repair enzyme system plays an important role in the response to platinum-based chemotherapy.It is possible to obtain prognostic predictors for the efficacy of chemotherapy by detecting the DNA repair gene polymorphism loci.Prediction of response to chemotherapy before treatment makes it possible to select those patients who are likely to benefit from the treatment.Clarification of the mechanism of resistance to chemotherapy is an important task to improve prognosis.ObjectiveTo reveal the correlation between the Neil2 gene rs8191670 polymorphism(T/C)and the sensitivity of cisplatin for non-small cell lung cancer.MethodsThe pathologic data of 206 patients with advanced NSCLC diagnosed in the First Affiliated Hospital of Zhengzhou University,which were involved and followed up from May 2011 to January 2017,were retrospectively reviewed.Taken 2ml peripheral venous blood of advanced NSCLC patients,then use RT-PCR and DNA sequencing detect the mutation of Neil2 mRNA 3'UTR in peripheral blood of NSCLC patients.Using multivariate analysis of variance analyse the relationship between clinical pathological features and mPFS of NSCLC patients.Kaplan-Meier method was used for survival analysis.The associations between the polymorphism of rs8191670 and sensitivity of platinum-based chemotherapy and security were evaluated by the log-rank test.Results1.T/C polymorphism was found in the rs8191670 site of Neil2 gene.Among 206 cases,There are 110 "T/T" homozygote cases,42 "C/C" homozygote cases and 54 “T/C” heterozygote cases.2.Multivariate analysis of variance results show that the clinicopathological features and chemotherapy regimens of NSCLC patients have no correlation with mPFS(P> 0.05),only gene types in rs8191670 loci have relation with mPFS(P = 0.02).3.Follow-up shows that the median PFS of patients bearing "T/T" homozygote on Neil2 gene rs8191670 were 6.1 months,significantly better than that of the "T/C" heterozygous patients(mPFS = 4.9 months,P < 0.01),and "C/C" homozygous patients(mPFS = 4.5 months,P < 0.01).4.The follow-up statistics result shows that three groups have no statistical difference in the incidence of adverse reactions(nausea,vomiting,diarrhea,leukopenia,anemia,thrombocytopenia,fever related-leukopenia)during chemotherapy treatment(P>0.05).ConclusionNeil2 gene rs8191670 have T/C polymorphisms,and change the damage repair capacity of DNA may through regulating the expression of Neil2 protein,thus affecting the efficacy of cisplatin chemotherapy.