| Bladder cancer(BC)is one of the most common malignant tumors of urinary system.Statistics shows that its recurrence rate and mortality rate are all high,ranking the first in urinary system tumors.In recent years,the number of confirmed cases of bladder cancer in the world has increased by 1.5 times.In our country,the number of cases in China has been found to increase year by year.Environmental and genetic factors have been involved in the development and development of bladder cancer.Cytotoxic T lymphocyte associated antigen 4(Cytotoxic T Lymphocyte-Associated Antigen-4,CTLA-4)gene is located on chromosome 2q33,the expression product of white cell surface antigen CD152 and CD28 by competitive binding ligand B7-1/B7-2,a negative regulator of T cell activation and proliferation,reduce the antitumor immune response low body,thereby increasing the susceptibility of tumor.With the development of human genomics research at home and abroad,many studies show that CTLA-4 single nucleotide polymorphism(single nucleotide polymerphisms,SNPs)is closely related with the genetic susceptibility to liver cancer,gastric cancer,breast cancer and other tumors;at the same time,there are very few foreign research shows that the correlation with the existence of bladder cancer.The purpose of this study is to analyze the distribution of CTLA-4 CT60G/A and-1661A/G polymorphisms in bladder cancer of Han nationality in Sichuan area,and to explore the correlation between CTLA-4 gene polymorphism and bladder cancer risk.Objective: Based on the analysis of CTLA-4 CT60 G/A and-1661 A/G single nucleotide polymorphisms(SNPs)loci in Chinese Han population of Sichuan,we can understand CTLA-4CT60 G/A,-1661 A/G alleles and genotype distribution.To investigate the relationship between the single nucleotide polymorphisms of CTLA-4CT60 G/A and-1661 A/G loci and the genetic susceptibility and clinical characteristics of bladder cancer.Methods :A case-control study was conducted to collect 241 cases of bladder cancer in Sichuan area of China,and 326 cases of healthy people(as control group);The peripheral venous blood of the subjects was collected,and the whole blood DNA was extracted by primer guidance to amplify the target gene.The Polymerase chain reaction restriction fragment length polymorphism(PCR-RFLP)was used to genotype CTLA-4 CT60G/A and-1661 A/G polymorphic loci,and DNA sequencing results were further verified.The distribution of genotypes and alleles of CT60 G/A and-1661 A/G polymorphic loci were identified in the two groups.The data were analyzed by SPSS 22 statistical software,and the relationship between CT60 G/A and-1661 A/G polymorphisms and the susceptibility of bladder cancer in Han nationality of Sichuan area was discussed.Using the t test or X2 test to compare the demographic characteristics,the control group was tested by X2 Hardy-Weinberg and X2 genetic equilibrium test;test case group and control group the corresponding test,comparison of genotype differences;whether there is a link between genetic susceptibility,clinical characteristics and environmental factors in non conditional logistic regression statistical analysis of different genetic model and bladder cancer,statistical results by odds ratio(odds ratio,OR)and 95% confidence interval(confidence interval CI)said,with P < 0.05 was statistically significant.Results:1.There was no significant difference between two groups(P> 0.05)in the age and slso in the gender.Smoking and drinking in the case group and the control group were significantly different(P<0.001,P=0.029).2.For the law of genetic equilibrium test by CTLA-4 on CT60G/A,-1661A/G control group,the statistical results showed no statistically significant P>0.05,two gene loci genotype difference,control group population frequency to meet the Hardy-Weinberg's law of inheritance balance,control group on behalf of good people.3.The distribution of genotype frequencies of 3.CTLA-4 CT60G/A loci in the two groups was statistically significant(X2 = 8.74,P=0.013),and the allele frequency distribution in the two groups was not statistically significant(X2 = 2.783.P=0.095);the genotype frequencies of CTLA-4-1661A/G locus in the two groups were statistically different(X2 = 7.689,P=0.021),and the allele frequency distribution in the two groups was statistically significant(X2 = 7.360,P=0.007).4.CTLA-4 CT60G/A GG can increase the risk of bladder cancer by 1.239 times,and OR(95% CI)is 1.239(1.039,1.478).P=0.017,after correction of confounding factors(such as gender,age,drinking and smoking),OR(95% CI)is 1.289(1.065,1.559),P=0.009.CTLA-4-1661A/G AG+GG can increase the risk of bladder cancer by 1.549 times,OR(95% CI)1.549(1.093~2.195),P=0.014;after correction of confounding factors(such as gender,age,drinking and smoking),OR(95% CI)is 1.696(1.162~2.474),P=0.006.In the allele model,the risk of bladder cancer increased significantly compared with the G allele and A allele,OR(95% CI)was 1.506(1.119~2.027),P value =0.007.5.In the CTLA-4 CT60G/A model further stratified analysis of dominant genes found in the age of more than 65 years of age,AG+AA genotype increased the risk of bladder cancer(P<0.05);the gender stratified analysis of smoking,no results statistical significance(P> 0.05);In the CTLA-4-1661A/G model of dominant genes further stratified analysis by age stratified analysis was not statistically significant(P> 0.05);hierarchical analysis of gender,the male-1661A/G AG+GG genotype increased the risk of bladder cancer(P<0.05);to study whether consumption stratification analysis,the results were not statistically significant(P> 0.05).6.The unconditional logistic regression analysis showed that there was no correlation between CTLA-4 CT60G/A gene models and clinical grading,staging and metastasis of bladder cancer by correcting smoking,drinking,sex and age.P value was not statistically significant(P> 0.05).In the CTLA-4-1661A/G loci,the dominant genotype AG/GG genotype was correlated with the staging and metastasis of bladder cancer.The OR,95% confidence interval and P value were 0.514(0.294~0.899),P=0.02,0.415(0.212~0.812)and P=0.01,respectively.Conclusion: 1.The CTLA-4 CT60 G/A genotype showed a signifi-cant difference in the distribution of the case group and the control group(P < 0.05);Logistic regression analysis showed that CT60G/A GG in bladder cancer risk increased by 1.239 times,P=0.017;A?G allele frequency distribution was not statistically significant(X2 = 2.783,P=0.095);no correlation between different genetic models and bladder cancer clinical grading,staging,metastasis(P > 0.05);it is not found that CTLA-4 CT60 G/A polymorphism is associated with susceptibility to bladder cancer.2.The genotype frequencies of CTLA-4-1661A/G loci were statisti-cally significant in the case group and in the control group(P < 0.05);Logistic regression analysis showed that:-1661A/GAG+GG increased the risk of bladder cancer by 1.696 times,P=0.014,G allele and A allele,the risk of bladder cancer in the population increased significantly(P=0.007);the dominant model was statistically significant with the staging and metastasis of bladder cancer(P<0.05).Therefore,the CTLA-4-1661A/G polymorphism is associated with the genetic susceptibility to bladder cancer in Sichuan Han population,and the AG/GG genotype may be associated with the staging and metastasis of bladder cancer. |
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