| Objective:Lung cancer is a malignant tumor.Its morbidity and mortality showing arising trend,in which non-small cell lung cancer(NSCLC) accounts for80%to85%,its survival rate is less than15%.Lung cancer is closely related tosmoking,air pollution and some occupational exposure which can’t fullyexplain the differences of incidence between different countries and differentgroups.There are some susceptible factors of some individuals to lung cancerresult from genetic mutation,deletion,gene polymorphism and other geneticfactors.There is important significance to investigate the molecularmechanisms of the genetic variation on lung cancer.Chemotherapy is the mainmethod to treat advanced NSCLC in which combined chemotherapy based onplain is usually used.However,clinical datas show a different reaction to thechemotherapy drugs result from the individual genetic factors,so the researchof sensitivity of chemotherapy can provide a scientific basis for individualizedtreatment.As the main active metabolite1,25(OH)2D3of Vitamin D which isan essential vitamin plays an important role in regulating calcium,phosphorus,tissue cells growth and differentiation,immune response and anti-tumormediated by vitamin D receptor(vitamin D receptor,VDR).It is confirmed thatVDR expressed by tumor cells can inhibit the proliferation anddifferentiation,reduce the size and number of tumor of the tumor afteractivated.Recently,with the researches rising,the relationship between VDRgene polymorphisms and cancer are controversial,and its main activemetabolite1,25(OH)2D3metabolism,regulate tissue cells growth anddifferentiation and,these functions is through vitamin D receptor(vitamin Dreceptor,VDR)mediated.Experiments confirmed that many tumor cells expressthe.after be activated,the receptor can inhibit the proliferation and differentiation of the tumor,reduce tumor size and number,in recent years,thereare more and more research on the relationship between VDR gene anddisease,these studies confirmed that VDR gene polymorphisms and cancer areclosely related,but the results are controversial.The research is to investigatethe relationship between the polymorphism of VDR gene(includedBsm1,Apa1,Taq1)and genetic susceptibility and chemotherapy sensitivity ofNSCLC to provide a theoretical basis for the clinical diagnosis and treatmentpathway.Methods：This is a case-control research,collect5ml vein anticoagulant blood of144patients with advanced NSCLC(The case group)and142healthy cases(the control group),and record their medical history and personal information.Extract the peripheral blood leukocyte DNA.The genotype of VDR geneBsm1,Apa1,Taq1loci were detected using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP).Compare the genefrequency,allele frequency,haplotype distribution and other relevant clinicaldata between the two groups.42cases of patients accomplish2cycles ofGP/GC program chemotherapy and check CT,then assess the efficacyaccording to RECIST criteria to divide them into:completeremission(CR),partial remission(PR),stability disease(SD),and progression ofdisease(PD).Set CR+PR for the effective,Set SD+PD for the ineffective.UseHardy-Weinberg balance analyze the data in control group.Use SPSS version13.0software package,there is significant difference if P<0.05.Compare ofdistribution of genotypes and allele between the case group and control groupand different genetype between the chemotherapy efficacy using chi-squaretest,Linkage disequilibrium analysis and haploid frequency using the SHEsissoftware.The relative degree of risk was expressed by95%confidence intervalindicate.Result:1. The proportion of smoking in advanced NSCLC group(72.9%)wassignificantly higher than in healthy control group(P<0.05). 2. The distribution of3genotype in VDR gene was consistent withHardy-Weinberg equilibrium(P>0.05).3. There is not significant difference in genotype distribution of Bsm1,Apa1,Taq1in VDR gene between advanced NSCLC group and healthy controlgroup(P>0.05).4. Stratified analysis according to smoking:There is difference betweencase group and control group in smokers.The smokers with aa genotype have ahigher risk of incidence than the ones with Aa+AAgenotype(OR=2.272,95%CI:1.223-4.223).5. There is no correlation between polymorphisms of three sites in VDRgene and squamous cell carcinoma and lung adenocarcinoma according to thestratified analysis.6. Multifactor regression analysis showed that smoking,gender are majorrisk factors for lung cancer.One of the men had advanced NSCLC danger is0.502times that of women(OR=0.502,95%CI:0.281-0.897);The danger ofsmokers happen advanced NSCLC is3.678times of smokers(OR=3.678,95%CI:2.068-6.541).7. There is no clear linkage disequilibrium among Bsm1,Apa1and Taq1in VDR gene.The haplotype of bat in control group of theproportion(0.041%)was significantly higher than that in case group(0.005%)(χ2=8.212,P=0.004).8. There is significant difference in chemotherapy efficiency amongpatients with different gender,age,smoking status,pathological type,chemotherapy program(P>0.05),and there is no association between3sites inVDR gene and chemosensitivity.Conclusion：1. Smoking may increase the risk of advanced NSCLC.2. There was no correlation among Bsm1,Apa1,Taq1in VDR gene andadvanced NSCLC.3. The smoker with genotype of aa in Apa1sites have a rising risk ofadvanced NSCLC. 4. Women,smoking are the main risk factor of advanced NSCLC.5. There is no clear linkage disequilibrium among Bsm1,the individualwith Apa1and Taq1in VDR gene and bat haploid type have a low risk ofadvanced NSCLC.6. There is no correlation between the polymorphism of Bsm1,Apa1andTaq1in VDR gene and chemotherapy sensitivity. |
PDF Full Text Request