Relationship Of Polymorphisms Of Vitamin D Receptor Gene And Susceptibility And Sensitivity To Chemotherapy Of Advanced Squamous Cell Carcinoma Of Lung

Objective:Pulmonary malignant tumor is one of the most serious threats to humanhealth, the morbidity and mortality of which in recent years shows a risingtrend. Squamous cell carcinoma of lung (SCC) belongs to one type ofmalignant lung tumor with poor prognosis that accounts for30%-40%of totallung tumor. Several factors can be associated with SCC. With the advent ofindustrial society, besides smoking, the influence of air pollution, professionalworking environment and so on, turns to be apparent. It’s shown from thestudy that muti-factors could not reflect the differences of incidence ofpulmonary malignant tumor between different countries, population groups aswell as regions. Nevertheless, certain susceptible factors that are determinedby genetic basis must be connected with the pathogenesis of pulmonarymalignant tumor. Susceptibility level of pulmonary malignant tumor fromindividuality may be transformed by somatic mutation, random inactivation ofX-chromosome, gene polymorphism and other genetic factors. Therefore,studying on differences in susceptibility resulted from genetic mechanism is ofgreat significance to the occurrence, development and prognosis of seriousdisease. Chemotherapy is the main method to treat advanced SCC. Currentclinical standard chemotherapy regimens are usually combined chemotherapyon the basis of platinum drugs. Moreover, numerous clinical data indicate thatthere are different individual responses to the drugs used in chemotherapy; inaddition, sensitivity of the differences from the same drugs may be determinedby the individual genetic factors.The study of chemotherapy sensitivity in thepatients with lung cancer could provide a scientific basis for the individualizedtherapy for lung cancer patients. Vitamin D, being steroidal derivatives, belongs to fat-soluble vitamin, which is an essential element for the humanbody. It can be obtained not only from food, but also from its precursor afterUV activation. The main active metabolite is1,25(OH)2D3, that hasimportant physiological and biochemical activity including regulation ofcalcium and phosphorus metabolism, regulation of tumor cell proliferation anddifferentiation, inhibition of tumor cell growth as well as induction ofapoptosis, the function of which mediates mainly through the receptor(vitamin D receptor,VDR). Many tumor cells in human body express VDR,through which mediated the tumor cells play a regulatory role. With theincreasing close relationship between research of VDR gene and tumor, lots ofstudies have confirmed VDR gene polymorphism has been strongly linked totumor, but the results are still in controversy. This research aims toinvestigate the relation between polymorphism of VDR gene (including Apa1,Taq1) and susceptibility and chemo-sensitivity of advanced squamous cellcarcinoma of Lung in order to find out potential risk factors from lung cancer,which could provide new theoretical bases for clinical exploration.Methods：Case-control study methods based on hospital has been employed, thatis, collecting62patients with lung squamous carcinoma and70individualintravenous anticoagulant5ml, in the meantime, recording their medicalhistory and personal information. Extract leukocyte DNA from peripheralblood, adopting the method of polymerase chain reaction--restrictionfragment length polymorphism (polymerase chain reaction-restrictionfragment length polymorphism，PCR-RFLP) to test the genotype of Apa1,Taq1in VDR gene. Set the CR+PR effectively, SD+PD is invalid. TakeHardy-Weinberg Genetic Equilibrium to analyze the datum in control group.Use SPSS13.0software package to make statistical analysis, there isstatistical significance if P<0.05. Take chi-square test to analyze thedistribution comparisons of genotype and allelotype in case group andcontrol group and differences in the efficacy of chemotherapy of differentgenotype, besides, compare the genotype frequency, allele frequency, haplotype distributions and relevant clinical data in two groups.46patientsof the total complete the GP/GC program: gemcitabine (GEM)+cisplatin(DDP)/carboplatin (CBP) after2cycle’s chemotherapy by CT, accordingto the RECIST standard, there are complete remission (CR), partialremission (PR). The SHEsis software has been taken to analyze VDR genepolymorphism loci linkage disequilibrium and haplotype frequencies. Theodds ratio (odds ratio, OR) and95%confidence intervals (confidenceinterval, CI) represents the relative risk degree.Result:1Smoking ratio (72.9%) in advanced SCC group is significantlyhigher than that in healthy control group (50.0%), which reveals remarkabledifference.2The genotype distribution of two sites of VDR gene in healthycontrol group is in accordance with Hardy-Weinberg equilibriumdistribution (P>0.05)3There is no statistical significance between genotype distribution ofApa1Taq1site in VDR gene and alleles distribution in advanced SCC incomparison with healthy control group(P>0.05).4Based on stratification analysis of smoking: in smoking group,statistical significance exists in Apa1sites of case group and control group;smokers carrying aa genotype increase incidence risk of SCC comparedwiththe smokers carrying Aa+AA genotype(OR=2.375,95%CI:0.957-5.895).In non-smoking group, smokers carrying Aa+AA genotype increaseincidence risk of SCC compared with the smokers carrying aagenotype(OR=0.100,95%CI:0.020-0.505).5Multi-factor regression analysis shows: smoking and gender are themain risk factors for advanced SCC. The incidence risk of male attacked byadvance SCC is0.491times than that of female (OR=0.491,95%CI:0.269-0.846); the incidence risk of smokers is4.013times higher than thatof non-smokers (OR=4.013,95%CI:2.798-7.261)6There is no remarkable linkage disequilibrium between Apa1and Taq1in VDR gene. Four haplotypes in case group and control group haveno significant difference in frequency distribution (p>0.05).7Two loci polymorphism in VDR gene and sensitivity to GP/GCchemotherapy has no correlation.Conclusion：1Smoking can make the incidence risk of advanced SCC increase.2There may be correlation between Apa1, Taq1in VDR gene andadvanced SCC.3The genotype of aa in Apa1sites can significantly raise the risk ofadvanced SCC in smokers; non-smokers carrying Aa+AA genotype in Apa1sites can augment the risk of advanced SCC.4Male and smoking are the main risk factors for advanced SCC.5There is no obvious linkage disequilibrium between Apa1and Taq1in VDR gene.6The polymorphism of Apa1and Taq1in VDR gene andchemotherapy sensitivity has no connection.