The Epidemiological Study On The Association Of Survival Factors, DNA Double-strand Break Repair Gene Polymorphisms With Survival In Lung Cancer Patients

[Objective] Lung cancer is the most common cause of cancer-related deathworldwide,also the leading cause of cancer-related death in china.The early diagnosticrate and survival rate in lung cancer is low.Currently, Surgery, chemotherapy andradiotherapy are the main treatment for lung cancer, but the outcome is notsatisfactory. Clinical studies have found that patients with the same clinicalcharacteristics and treatment still have large differences in prognosis. Therefore,exploring the prognostic factors in lung cancer is very important for individualizedtreatment. One aim of this study is to analyze the1-year,3-years and5-year survivalrate of primary non-small cell lung cancer (NSCLC) patients in Fujian area.Based onthis,we also investigated the primary NSCLC patients’ demographic characteristics(age, gender, culture degree of smoking status, etc.);clinical features(histopathologictype,TNM staging, tumor size, lymph node metastasis, etc.) and treatment strategy(surgery,chemotherapy,and radiotherapy) as risk factors on prognosis.We also studiedthe association between DNA double-strand break repair gene（XRCC3、XRCC4、BRCA1、BRCA2、NBS1）polymorphisms in patients with non-small-cell lung cancerprognosis.[Method] A total of1114patients with primary non-small cell lung cancer (NSCLC)were enrollde in this study. Clinical data were collected using “Healthy habits anddisease history questionnaire” by face to face interview and “Lung cancer survivalanalysis questionnaire” by looking up electronic medical record in Record room.5mlblood sample was collected from each patients, the genomic DNA was extracted fromall blood.TaqMan probe technique were used to identify the polymorphism of DSBR gene XRCC3（rs6869366、rs1056503、rs3734091）、XRCC4（rs861539、rs861537、rs1799794）、BRCA1（rs16942）、BRCA2（rs144848）、NBS1（rs1805794、rs2735383）.Telephone follow-up was conducted every six months from the date of diagnosis forpatients,checking the clinical information,treatment and survival status.the deadlineof follow-up was December1,2013. The survival information of patients who werelost contact were seeked from the public security bureau,provincial CDC deathregistration system according to the ID number,or call the local114according to thehome address to contact the local government for survival information.Among all the1114NSCLC patients,1019cases were successfully followed up, accounting for91.5%,95cases were lost, accounting for8.5%.All data was input using a double entry method with Epidata3.1software,SPSS19.0was used to analyze statistics. χ2test was used to describe thedistribution of Demographic characteristics,clinical data and genotype betweensuccessful followed-up lung cancer patients and lost followed-up patients (analysis forclassified variable); Kaplan-Meier was used to draw Survival curve and calculate for1,3,5years of survival rate and the median survival time;Cox proportional hazardmodel was used for single and multiple factors analysis, exploring the prognosticfactors of lung cancer from the aspects of individual factors, tumor clinical features,therapeutic method and genetic factors.[Results]1.1114Patients were recruited from the First Clinical Medical College and theAffiliated Union Hospital of Fujian Medical University and Fuzhou General Hospitalwith bronchoscopy and pathologic confirmation, Since December2006to December2012.Among them,1019cases were successfully followed up, accounting for91.5%,95cases were lost, accounting for8.5%;731cases were dead,accounting for65.6%,288cases were live,accounting for25.9%.Among the679NSCLC cases whowere identified the polymorphism of DSBR gene,there were611cases weresuccessfully followed up, accounting for90.0%,68cases were lost, accounting for10.0%,96cases were live, accounting for14.1%,515cases were dead,accounting for75.8%.General demographic characteristics and clinical data distribution were no Statistically significant differences between successfully followed-up patients and lostpatients,which demonstrated that the samples have certain representativeness.2. The median survival time(Median Survival Time，MST) of NSCLC patientswas25±0.976months(95%CI=23.088-26.912),1,3,5year survival rate was76.5%、36.9%、24.2%respectively。3. Single factor analysis showed: gender,age, BMI, smoking, KPS score, tissuetypes, tumor clinical staging, tumor size, primary transfer,pleural invasion,Pleuraleffusion,lymphatic metastasis, blood line transfer, surgical excision, surgical excisionway, chemotherapy,cycles of chemotherapy, treatment strategy, comprehensivetreatment,Character were the prognostic factors for NSCLC patients.4. Multi-factor analysis showed: smoking,pathological types, tumor Clinicalstaging, tumor size,primary transfer, surgery, chemotherapy,cycles of chemotherapy,Character were independent prognostic factors for NSCLC patients.5. NBS1rs2735383gene polymorphism were the independent prognostic factorsin patients with advanced NSCLC treated with chemotherapy.The median survivaltime for the patients with (GG+GC) genotype was23months (95%CI=19.11-26.89),while21months(95%CI=16.70-25.30) for the patients with CC genotype.The HazardRate(HR) for the patients with CC genotype was1.42times (95%CI=1.01-1.95，P=0.045) than patients with (GG+GC) genotype. More significant association existedin advanced lung squamous cell carcinoma treated with chemotherapy, patients withNBS1rs2735383(GG+GC) genotypes had significantly longer survival time thanpatients with CC genotype(PLog-rank=0.043；HR=1.99；95%CI=1.01-3.94).The HazardRate(HR) for the patients with lung squamous cell carcinoma with CC genotype was1.82times(95%CI=1.07-3.10，P=0.028) than the patients with (GG+GC) genotype.6. BRCA1rs16942gene polymorphism were the independent prognostic factorsin patients with early lung squamous cell carcinomas,early patients treated withchemotherapy,and no-smoking early NSCLC. The hazard rate for patients with earlylung squamous cell carcinomas with (AG+GG) was1.74times (95%CI=1.04-2.93，P=0.037) than patients with AA genotype; For early patients treated withchemotherapy, the hazard rate for patients with (AG+GG) genotype was1.55 times(95%CI=1.05-2.29，P=0.027) than patients with AA genotype. No-smokingearly NSCLC with (AG+GG) genotype had a higher risk of death than patients withAA genotype(HR=1.96,95%CI=1.04-3.70,P=0.038).7. The hazard rate for lung adenocarcinoma patients(Ⅲ period) treated withsurgery with NBS1rs1805794(CG+GG) genotype was0.49times(95%CI=0.23-1.01，P=0.054) than patients with CC genotype.NBS1rs1805794(CG+GG) genotype may be the prognostic favourable factor for lung adenocarcinomapatients(Ⅲ period) treated with surgery.[Conclusion] smoking, pathological types, tumor Clinical staging,tumor size,primarytransfer,surgery, chemotherapy,cycles of chemotherapy,Character were independentprognostic factors for NSCLC patients;NBS1rs2735383and BRCA1rs16942genepolymorphism may affect the survival time for the NSCLC patients treated withchemotherapy,which may be the reference to clinical therapeutic strategy; NBS1rs1805794and NBS1rs2735383gene polymorphism were associated with theprognosis of NSCLC patients treated with surgery,which may be the biomarker forPredicting survival.