The Study Of Genetic Association Between Single Nucleotide Polymorphisms Of IL6、IL10、KIF1B And Susceptibility To Primary Hepatic Carcinoma

Objective1. To investigate the risk factors related to environment in primary hepatic carcinoma(PHC).2. To analysis the association between single nucleotide polymorphisms of IL6,IL10,KIF1B and susceptibility to Primary hepatic carcinoma.3. Comprehensive analysis of the role of gene-gene and gene-environment interactions inPrimary hepatic carcinoma.MethodsIn order to explore the risk factors of Primary hepatic carcinoma, we conducted ahospital-based1:1matched case-control study and adopted the epidemiologicalquestionnaire. The306paired subject mainly came from the First People’s Hospital ofShunde. Candidate polymorphisms were genotyped by Taqman fluorescence quantitativePCR methods. We used the conditional logistic regression analysis to investigate thecorrelation of IL6, IL10and KIF1B single nucleotide polymorphisms and the risk ofprimary liver cancer. We also applied a comprehensive statistical strategy to investigate therole of gene-gene and gene-environment interactions in Primary hepatic carcinoma bycrossover analysis combining with multifactor dimensionality reduction (MDR).Results1. We found factors including family with per capita monthly income, history ofdrinking, history of eating raw fish，history of HBV infectious, history of hepatocirrhosis and the family history of HBV and PHC，which have some association with PHC bymultifactorial condition logistic analysis. OR(95%CI)=0.29(0.10-0.88),2.45(1.24-4.82),1.99(1.06-3.75),12.02(6.02-24.00),8.50(3.48-20.81),2.78(1.29-5.97),6.90(2.10-22.73).2. Chi-square test was used to calculate the characteristics of genotypes distributionbetween cases and controls.There were no statistically significant difference among the fiveselected SNP in two groups (all P＞0.05). Stratification analysis showed that afterstratified with history of HBV, no risk increasing genotype was found.3. There was no statistically significance among rs1800796in IL6, rs1800871andrs1800872in IL10, rs17401966and rs3748578in KIF1B through some anaysis.4. Significant pair-wise multiplicative and negative additive gene-gene interaction wereobserved between IL6(rs1800796) and KIF1B(rs3748578) by crossover analysis.OR(95%CI)=2.11(1.08-4.13),S=0.04,AP=0.65, RERI(95%CI)=0.60(0.10-1.11). Rs1800796and rs17401966also showed negative additive interaction. S=-0.19, AP=0.53,RERI(95%CI)=0.58(0.02-1.14). Further MDR analysis in whole subjects showed the bestMDR model was the two-factor model including rs1800796and rs3748578in gene-geneinteration (TA=53.76%, CVC=10/10，P=0.366). But we didn’t find any significantlymultiplicative or additive interaction between gene and environment when in analysis ofcrossover or MDR.Conclusions1. The main risk factors of PHC including history of drinking, history of eating rawfish，history of HBV infecious, history of hepatocirrhosis, family history of HBV and PHC.The factor of family with per capita monthly income has a negative correlation with PHC.The risk of PHC decreased when the respondents earn more than3000yuan per month.2. Interaction between rs1800796in IL6and rs17401966in KIF1B contributedsignificantly to PHC.3. It is may be inherent association between IL6/STAT3and KIF1of Wnt/β-cateninsignaling pathway.