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The Association Of IL-8,10 Polymorphisms With Breast Cancer Risk In A Chinese Han Population

Posted on:2019-02-12Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y Z HeFull Text:PDF
GTID:1364330545998383Subject:Surgery
Abstract/Summary:PDF Full Text Request
Part One Association between IL-8-251A/T,-353A/T and+396T/G polymorphisms and risk of breast cancer in a population of ChinaBackgroud:1 The incidence of breast cancer is increasing gradually with the increasing pace of people's life.The pathogenesis of breast cancer is unknown at this stage,and the main diseases are due to environmental factors and genetic factors.It plays a role in the occurrence and development of breast cancer.IL-8 as regulating factor exists in the immune system,and its gene single nucleotide polymorphisms of gene transcription and protein expression will has some impact,its role in the immune condition,in turn,affects the occurrence and development of tumor.2 With the continuous development of biological engineering and molecular biology technology,gene analysis technology is widely used in the study of biological characteristics of breast cancer,making the treatment of breast cancer into the age of gene therapy.There are a lot of studies showing that breast cancer has a unique gene site.In order to provide an important reference for improving the therapeutic effect of breast cancer,the relevant analysis of the corresponding gene loci and the risk factors of breast cancer can be made in order to formulate the individualized treatment plan.3 Interleukin 8(Interleukin-8,IL-8)is a human physiological and pathological development plays an important role in the process of cytokines,numerous studies show that the factors in the occurrence,proliferation and metastasis of malignant tumor,and many other play a crucial role in the process,and participate in the entity formation and growth of malignant tumor blood vessels.Objective:1 A randomized controlled study of IL-8-251,-353,and +396 loci for breast cancer and the same number of normal population at the same time was conducted to analyze the correlation between the loci and breast cancer,providing a new genotype for the prevention and control of breast cancer.2 To research the relationship of IL-8 for breast cancer in the general population with the menarche age,body mass index,time,physical exercise and birth lactation time and the occurrence of breast cancer research analysis,providing a new method for breast cancer.Methods:This experiment mainly used the pathology-comparison research method,in terms of research object mainly chose Inner Mongolia people's hospital and wuhan university people's hospital of 411 cases of mammary gland surgical breast cancer patients and 411 healthy controls in China,based on the epidemiological investigation.For patients with peripheral venous blood,then need to extract genomic DNA patients,the case group and the control group using PCR technique to IL-8-251 gene loci,and-353 gene loci + 396 gene loci of single nucleotide polymorphisms were analyzed.And analyzes the distribution of genotypes in the case group and the control group,this experiment mainly used the chi square test,Logistic regression and other methods,the correlation of multiple genes and breast cancer risk.Breast cancer group and normal control group were using EDTA anticoagulant tube collecting peripheral venous blood,from the whole blood chromosome DNA was extracted by phenol chloroform method,using each specimen with NanoDrop and qualitative and quantitative detection of DNA gel electrophoresis method,testing after-80? temp-erature storage place.After hybridization of i1-8-251A/T,-353 A/T and +396G/T,the amplification results were detected by 2%agarose gel electrophoresis.Results:1 411 cases of breast cancer and 411 healthy controls were selected;The mean age of the group was 57.47 plus or minus 9.69 years,and the mean age of the control group was 58.10 plus or minus 8.55 years.There was no statistically significant difference between the two groups of menopausal status,reproductive history,breast-feeding,smoking and drinking history.The average body mass index of the case group was 23.42 plus or minus 3.07(kg/m2),and the control group was 22.10 plus or minus 3.14(kg/m2).The mean age of the initial wave was 12.48 plus or minus 2.24 years,and the control group was 13.41 plus or minus 2.60 years old.The case group had lower physical activity;The mean age of the first pregnancy was 25.73 plus or minus 3.24 years,and 24.77 plus or minus 3.24 years in the control group.In the case group,the breast-feeding time was 5.27,plus or minus 2.71 months,and the control group was 6.34 plus or minus 2.87 months.There were 91 cases and 58 cases in the control group.The duration of hormone use in the case group was 8.33 plus or minus 3.30 months,and the control group was 4.38 plus or minus 1.63 months.The difference was statistically significant.2 -251 A/T locus TT genotype frequency in the proportion of breast cancer cases in the concrete is 38.69%,TA genotype frequency in the proportion of breast cancer cases in the concrete is 43.55%,AA genotype frequency in the proportion of breast cancer cases in the concrete is 17.76%;Healthy controls,the TT genotype frequency in healthy control group 50.36%proportion of concrete,TA genotype frequency in the proportion of specific health control group was 39.42%,AA genotype frequency in the proportion of specific health control group was 10.22%.The difference was statistically significant.3 -353 A/T siteTT genotype frequency in the proportion of breast cancer cases in the concrete is 47.69%,the AT genotype frequency in the proportion of breast cancer cases in the concrete is 40.39%,AA genotype frequency in the proportion of breast cancer cases in the concrete is 11.92%;Healthy controls,-353 A/T loci TT genotype frequency in healthy control group share of 48.66%,specific site AT genotype frequency in the proportion of specific health control group was 43.07%,AA genotype frequency in the proportion of specific health control group was 8.27%,the difference is statistically significant.4 + 396 T/G loci TT genotype frequency in the proportion of breast cancer cases in the concrete is 86.86%,TG genotype frequency in the proportion of breast cancer cases in the concrete is 12.17%,GG genotype frequency in the proportion of breast cancer cases in the concrete is 0.97%;Healthy controls,+ 396 T/G loci TT genotype frequency in the proportion of specific health control group was 89.05%,TG genotype frequency in the proportion of specific health control group was 10.46%,GG genotype frequency in the proportion of specific health control group was 0.49%,the difference is not statistically significant.Conclusion:IL-8-251 A/T polymorphic loci associated to A great extent Chinese female breast cancer susceptibility crowd,mutation of A gene for breast cancer in women have A higher risk,see it as A molecular marker for screening.The results of polymorphism ofIL-8-353A/T,+396T/G gene locus showed that the risk of breast cancer was not associated with Chinese women.Part Two Association between Gene Polymorphisms of Interleukin-8 and Interleukin-10 and Breast Cancer Susceptibility:Evidence Based on a Meta-analysisObjective:To explore Breast cancer susceptibility means only a small number of women are diagnosed with breast cancer in the same living condition.SNP is the change of single nucleotide sequence,a large number of genetic markers appear,and then the genome sequence appears polymorphism.This paper mainly studies the association between interleukin il-8,251A/T and il-10 819T/C polymorphism and the susceptibility of breast cancer,providing an important reference for the prevention and treatment of breast cancer.Methods:Consulting the literature,data analysis,Q test and 12 statistics and other methods of investigation and analysis combined.PubMed,CNKI and EMBASE have a large number of data about IL-8 and IL-10 polymorphisms and breast cancer.Through literature quality comparison and screening,the data and data related to the research are obtained,and the data are retrieved in January 2018 25th deadline.The data were analyzed by STATA 12.0 software,and the relationship between IL-8 251A/T and IL-10 819T/C gene polymorphism and breast cancer infection was studied mainly from two indexes.Two The indexes were Odds ratio(OR)and 95%confidence interval(CI)respectively,and were analyzed respectively from race and control groups.The heterogeneity of the study was obtained by performing Q test and 12 statistic on the data.In addition,sensitivity analysis was carried out.Finally,Begg's funnel chart and Egger's test were used to evaluate the bias.Results:1 Meta-analysis of the association between IL-8 and breast cancer showed that IL-8 gene polymorphism was not associated with susceptibility to breast cancer;correlation analysis at race level showed that the T allele of the population is negatively correlated with both breast cancer susceptibility(T vs.A:OR=0.73,95%CI=0.62-0.86;TT vs.AA:OR = 0.54,95%CI=0.40-0.74;AT+TT vs.AA:OR = 0.73,95%CI = 0.57-0.95;TT vs.AT+AA:OR = 0.60,95%CI = 0.46-0.77).From the control group level correlation analysis showed that people carrying the T allele and breast cancer susceptibility both negatively correlated(T vs.A:OR=0.03,95%CI=0.70-0.98;AT+TT vs.AA:OR=0.78,95%CI=0.65-0.94).In addition,the genetic model of each genotype does not have obvious publication bias,to a certain extent,that the results obtained by the above analysis is more reliable.2 Meta-analysis of the association between IL-10 and breast cancer showed that there was no significant correlation between IL-10 gene polymorphism and susceptibility to breast cancer.And the results showed that There was no significant correlation between genotype genetic model and breast cancer(C vs.T:OR=1.02,95%CI = 0.90-1.16;TC vs.TT:OR = 1.04,95%CI = 0.86-1.26;CC vs.TT:OR = 1.11,95%CI = 0.85-1.44;TC+CC vs.TT:OR = 1.04?95%CI = 0.87-1.25;TT vs.TC+TT:OR = 1.02,95%CI = 0.82-1.27).In addition,the genetic model of each genotype does not have obvious publication bias,to a certain extent,that the results obtained by the above analysis is more reliable.Conclusion:Meta-analysis of the data obtained IL-8 251A/T and IL-10 819T/C gene polymorphisms and breast cancer susceptibility was not significantly associated;but from the race and the control group showed that both levels of IL-8 There is a direct relationship between genotype TT and breast cancer.The study has some limitations,so the conclusions still need to be further examined.
Keywords/Search Tags:IL-8-251A/T, IL-8-353A/T, IL-8+396T/G, Polymorphism, Breast cancer, Susceptibility, Interleukin 8, Interleukin 10, Meta-analysis
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