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The Potential Functional Variants In TLR4Promoter Region And Gene-environment Interactions Contribute To Genetic Susceptibility Of Primary Liver Cancer: A Case-control Study In Shunde Area

Posted on:2015-05-03Degree:MasterType:Thesis
Country:ChinaCandidate:Y Y LiaoFull Text:PDF
GTID:2284330452953754Subject:Epidemiology and Health Statistics
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Objective1. To investigate the risk factors related to environment in primary liver cancer (PLC)of Shunde area.2. To investigate the association between toll-like receptor4genetic variation inpotential function and primary liver cancer.3. Comprehensive analysis of the gene-environment interactions with primary livercancer in Shunde population.MethodsThis hospital-based case-control study population included480patients with newlydiagnosed PLC, identified by the Shunde First People’s Hospital. The480cancer-freecontrols we included in the same period were randomly selected from the same hospitals,and were matched to the cases by sex, age, region. We used the unconditional logisticregression analysis to investigate the correlation of TLR4single nucleotide polymorphismsand the risk of primary liver cancer. We also applied a multiplicative model and additivemodel to investigate the role of gene-environment interactions in PLC.Results1. The multiplicative analysis of the risk factors related to environment in primaryliver cancer. We found factors including The type of occupation, BMI index, history ofdrinking, experience of drinking pond-ditch water, participating in sports, HBV infectious,the family history of HBV,the family history of PLC and the family history ofcarcinoma which have some association with PLC by multifactorial uncondition logisticanalysis. OR(95%CI)=0.62(0.45-0.84),0.50(0.35-0.72),1.75(1.29-2.37),1.60(1.17-2.17),0.57(0.42-0.78),7.50(5.51-9.66),1.85(1.23-2.79),2.16(1.07-4.38),1.64(1.04-2.59).Theresults suggest drinking,drinking pond-ditch water,HBV infectious,the family history ofHBV,PLC and cancer may be the independent risk factors of PLC. And the unemployed,overweight, participating in sports may be the independent protective factors of PLC.2. The association between toll-like receptor4genetic variation in potential functionand primary liver cancer.the differences in genotype frequencies distribution at rs10759932between the cases andcontrols were significant(P=0.0424).3. Compared with the TT genotype, individuals carrying CT genotype of rs10759932had a significant reduced risk of PLC(adjusted OR=0.74;95%CI=0.54-0.99).There were nosignificant differences in the distribution of haplotypes formatted by rs10116253,rs10759932, rs11536889site between the two groups.4. The gene-environment interaction analysis with the PLC. Significant multiplicativeand additive interaction were observed between rs10116253polymorphisms and drinkingby crossover analysis. The interaction analysis indicated that there was a multiplicativeinteraction and additive interaction between rs10116253polymorphisms and the familyhistory of HBV. And there was a multiplicative interaction between rs11536889polymorphisms and the family history of cancer. Critical statistical multiplicativeinteraction were observed between haplotype and drinking, haplotype and family history ofHBV;And there was a additive interaction between haplotype and and drinking, haplotypeand family history of HBV. Significant multiplicative interaction were observed betweenhaplotype and drinking pond-ditch water.Conclusions1. The results suggest drinking,drinking pond-ditch water,HBV infectious,the familyhistory of HBV, PLC and cancer, the family history of carcinoma may be the independentrisk factors of PLC. And the unemployed, overweight, participating in sports may be the independent protective factors of PLC.2. There is a certain correlation between rs10759932polymorphisms and PLC, and CTgenotype is a protective factor.3. Significant interaction were observed between rs10116253polymorphisms anddrinking, rs10116253polymorphisms and the family history of HBV, rs11536889polymorphisms and the family history of cancer, haplotype and drinking, haplotype andfamily history of HBV, haplotype and drinking pond-ditch water in the interaction analysis.Compared with the genetic variation of single function, the genetic variation of TLR4andenvironment interaction effects on PLC susceptibility is more important.
Keywords/Search Tags:Primary hepatic carcinoma, The potential functional variants, Risk factors, Interacition
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