| Objective:Lung cancer is one of the malignant tumors that has serious threat to human’s health. It has high morbidity, poor treatment outcome, and high death rate. Squamous Cell Carcinoma of Lung(SCC) accounts for about 1/3 of lung cancer. As its rapid disease progression and relatively poor prognosis, exploring the related prognostic factors in SCC has become a research hot spot.Many patients with advanced SCC have lost the chance of operation, platinum-based combination chemotherapy is the standard first-line chemotherapeutic regimen. Vitamin D receptor(VDR) can inhibit tumor proliferation, reduce the volume of tumor, reduce the number of tumor cells and so on. It generally exists in every tissue cell in the human body, lymphocytes, colon and lung cells with over level expression. This research investigates the relationship between polymorphism of VDR gene(including Apa1, Taq1) and susceptibility, chemotherapeutic effect and prognosis of SCC in order to find out the potential risk factors and the influence factors of chemotherapeutic effect and prognosis for SCC, which could provide new theoretical bases for clinical exploration.Methods:Individual elbow venous blood 5ml was collected, and then was treated with anticoagulation sodium citrate.The blood samples were collected from 288 cases of patients with SCC and 284 healthy individuals, recording their medical history and personal information. Leukocyte DNA from peripheral blood was extracted. The method of polymerase chain reaction--restriction fragment length polymorphism(PCR-RFLP) was applied to test the genotype of Apa1, Taq1 in VDR gene.SPSS17.0 statistical software was used to make statistical analysis.The distribution comparisons of genotype and allelotype in case group and control group were analyzed by chi-square test.The main risk factors of SCC were analyzed by logistic multifactor regression. The odds ratio(OR) and 95% confidence intervals(95%CI) represent the relative risk degree. Hardy-Weinberg Genetic Equilibrium was taken to analyze the datum in control group. The SHEsis software was taken to analyze polymorphism loci linkage disequilibrium and haplotype. 4 cycle’s GP/GC chemotherapy were accepted by 54 patients. The recent curative effect was evaluated according to 1.1 Response Evaluation Criteria in Solid Tumors(RECIST 1.1). Chi-square test was taken to detect the difference of chemotherapeutic efficay between patients with different clinical features and difference among different genotypes.92 cases of patients with SCC were successfully followed up to do prognosis analysis. Kaplan-Meier survival analysis and Log-rank test were taken to analyze the relationship between two loci of different genotypes and survival time of patients with SCC.Cox regression model was used to analyze the influence factors of the prognosis of patients with SCC.Result:1. Susceptibility analysis: Logistic regression analysis shows: VDR Taq1 gene polymorphisms and smoking are risk factors of SCC. The SCC risk of tt+Tt genotype carriers is 0.556 times than the TT genotype carriers(OR=0.556,95%CI:0.393-0.785); The SCC risk of smokers is 1.622 times than non-smokers(OR=2.2392,95%CI:1.660-3.449).Based on stratification analysis of smoking: In smoking group, there is statistical significance in Taq1 gene polymorphisms; the SCC risk of tt+Tt genotype carriers is 0.049 times than the TT genotype carriers(OR=0.049,95%CI:0.259-0.929).There is statistical significance in t allele and T allele; the SCC risk of t allele carriers is 0.444 times than the T allele carriers(OR=0.444,95%CI:0.241-0.817).2. Efficacy analysis of chemotherapy: The difference of VDR Apa1 in genotype frequencies between disease control group and disease progression group has no statistical significance(χ2=0.548,p=0.459); The difference of VDRTaq1 in genotype frequencies between disease control group and disease progression group has no statistical significance(χ2=0.699,p=0.403).3. Prognostic analysis: there are no significant correlations between the VDR Apa1 gene polymorphism and other Clinical features(including gender, smoking, age, lymph node metastasis, clinical stage, operation and chemotherapy). VDR Taq1 gene polymorphism is not associted with other clinical features referred in the research.Kaplan-Meier survival analysis, Logrank test results show that VDR Apa1 gene polymorphism is associated with the median survival time of patients with SCC(χ2=3.968,p=0.046);compared with Aa+AA genotype carriers, aa genotype carriers have longer median survival time(24 months VS 16 months).Cox regression analysis shows that VDR Apa1 polymorphisms, clinical stage, operation and chemotherapy influence the prognosis of patients with SCC. The relative risk Exp(B) is 1.002, 0.519, 2.690, 4.779 and 4.358. Corresponding 95% confidence intervals are [0.676~1.487], [1.606~4.508], [1.414~20.772] and [2.387~20.487]. The risk of death in aa genotype carriers is 0.712 times than the Aa+AA genotype carriers. The risk of death in patients with early SCC is 0.519 times than the patients with advanced SCC. The risk of death in non- surgical patients is 4.779 times than the surgical patient. The risk of death in patients without chemotherapy is 4.358 times than the patients undergoing chemotherapy. There is no significant correlation between Taq1 polymorphism and the prognosis of patients with SCC.Conclusion:1. Taq1 polymorphism is related to genetic susceptibility of SCC. The tt+Tt gene reduces the risk of SCC. The t allele is negatively correlated with the risk of SCC. Smokers with tt+Tt gene are significantly reduced the risk of SCC.2. There is no significant correlation between VDR Apa1, Taq1 genetic polymorphisms and the efficacy in patients undergoing chemotherapy.3. There is correlation between VDR Apa1 gene polymorphisms and the prognosis of patients with SCC. The aa genotype is related with the better prognosis of patients with SCC. There is no significant correlation between Taq1 gene polymorphism and the prognosis of patients with SCC. |
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