Relationship of Vitamin D Receptor Gene Polymorphisms with Advanced Adenocarcinoma of Lung Cancer Susceptibility and Senstivity to Chemotherapy
|School||Chengde Medical College|
|Keywords||Vitamin D receptor Non-small cell lung cancer Gene polymorphism Susceptibility Chemotherapy sensitivity|
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 lungcancer result from genetic mutation,deletion, gene polymorphism and othergenetic factors.There is important significance to investigate the molecularmechanisms of the genetic variation on lung cancer.The research is toinvestigate the relationship between the polymorphism of VDRgene(included Bsm1,Fok1)and genetic susceptibility and chemotherapysensitivity of advanced adenocarcinoma of lung to provide a theoreticalbasis for the clinical diagnosis and treatment pathway.Methods：This is a case-control research, collect5ml vein anticoagulant bloodof172patients with advanced adenocarcinoma of lung (The casegroup)and180healthy cases (the control group),and record their medicalhistory and personal information.Extract the peripheral blood leukocyteDNA.The genotype of VDR gene Bsm1,Fok1loci were detected usingpolymerase chain reaction-restriction fragment lengthpolymorphism(PCR-RFLP).Compare the gene frequency, allelefrequency,haplotype distribution and other relevant clinical data betweenthe two groups.52cases of patients accomplish2cycles of GP/GCprogram chemotherapy and check CT,then assess the efficacy according to RECIST criteria to divide them into：complete remission(CR),partialremission(PR),stability disease(SD),and progression of disease(PD).SetCR+PR for the effective,et SD+PD for the ineffective.UseHardy-Weinberg balance analyze the data in control group.Use SPSSversion13.0software package,there is significant difference ifP<0.05.Compare of distribution of genotypes and allele between the casegroup and control group and different genetype between thechemotherapy efficacy using chi-square test,Linkage disequilibriumanalysis and haploid frequency using the SHEsis software.The relativedegree of risk was expressed by95%confidence interval indicate.Result:1. The proportion of smoking in advanced adenocarcinoma of lunggroup(49.4%)and healthy controls (47.8%), no significant difference.2. Genotype of VDR gene in2healthy control group of2locidistribution was in consistent with Hardy-Weinberg equilibrium (P>0.05).3. There is significant difference in genotype distribution advancedlung adenocarcinoma group VDR gene Bsm1genotype distribution wasstatistically significant (χ~2=8.111,P<0.05) and allele distribution comparedwith the healthy control group was statistically significant (χ~2=6.492,P<0.05).The Fok1genotype distribution in comparison with healthy controlgroup was statistically significant (χ~2=10.379,P<0.05), and its alleledistribution is compared with the healthy control group had no statisticalsignificance (P>0.05).4. According to whether smoking stratified analysis: smoking groups,Bsm1, Fok1loci were not significant in the case group and the control group(P>0.05). Non-smokers, Bsm1genotype distribution was statisticallysignificant and allele distribution compared with the healthy control groupwas statistically significant (χ~2=7.947,P<0.05).The Fok1genotypedistribution in comparison with healthy control group had no statisticalsignificance (P>0.05),and its allele distribution is compared with the healthycontrol group had no statistical significance. 5. Multiple regression analysis showed that sex is a major risk factorfor the occurrence of advanced lung adenocarcinoma.The risk of maleoccurrence of advanced lung adenocarcinoma is feminine0.492times(OR=0.492,95%CI:0.283-0.889).6. Among the VDR genes Bsm1and Fok1does not exist significantlinkage disequilibrium.4kinds of haplotypes in patient group and controlgroup had no statistical significance (P>0.05).7. Between VDR gene2polymorphism and the sensitivity to GP/GCchemotherapy without correlation (P>0.05).Conclusion：1. The VDR associated gene Bsm1polymorphism and advanced lungadenocarcinoma risk.The Bsm1B allele may increase the risk of lungcancer.2. The VDR gene Fok1polymorphism and advanced lungadenocarcinoma risk may be associated with.3. Women are the main risk factors for advanced lung adenocarcinoma.4. Between the VDR gene Bsm1, Fok1does not exist significantlinkage disequilibrium.5. Between the VDR gene Bsm1, Fok1polymorphism andchemosensitivity of no correlation.6. Smoking may not increase the risk of advanced lungadenocarcinoma.