| Objective:To explore the correlation between genetic polymorphisms in IGF-2, IGF-2R, IGF-1R and genetic susceptibility to hepatocellular carcinoma in the high incidence area of guangxi province, and to find out whether there was gene-gene or gene-environmental factors interaction between them.Methods:A population-based case-control study was conducted, which included113patients with hepatocellular carcinoma and113normal controls. All of the cases and controls were based on the Screening High-Risk Populations for HCC in the high incidence area of guangxi province. The genetic polymorphisms of IGF-2, IGF-2R, IGF-1R were determined by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Epidemiological data were collected using a structured questionnaire. The distributions of demographic characteristics, genotype frequencies and epidemiological features between cases and controls were analyzed by χ2-test. Odds ratios (ORs) with95%confidence intervals (CIs) for the association between genotype frequencies and HCC were estimated by logistic regression models, after controlling for other covariates. Gene-environmental and gene-gene interaction were analyzed by the multiplication model of crossover analysis and logistic regression.Results:1. No significant deviations from the Hardy-Weinberg equilibrium were observed for IGF-2, IGF-2R, IGF-1R polymorphisms in healthy controls. The allele frequencies in our control population represented the allele frequencies in the general population.2. There was a significant difference for alcohol consumption(χ2=8.816, P=0.003) and detection of HBsAg(χ2=63.215, P=0.000) between the patients and healthy controls. Alcohol consumption could be an increased risk for hepatocellular carcinoma(OR=2.256,95%CI=1.313～3.874). Detection of HBsAg had a significantly higher risk(OR=11.289,95%CI=5.948～21.423) for hepatocellular carcinoma. There was no significant difference between cigarette smoking and hepatocellular carcinoma(χ2=3.476, P=0.062).3.(1), The distribution frequency for IGF-2genetypes was AA(11.5%), AG(25.7%), GG(62.8%) in HCC patients, AA(10.6%), AG(36.3%), GG(51.3%) in healthy controls. There was no significant difference for distribution frequency of IGF-2genotypes between the patients and healthy controls (χ2=3.021, P=0.221). There was no significant difference in the allele frequency distribution between HCC patients and healthy controls (χ2=0.045, P=0.832). (2), The distribution frequency for IGF-2R genetypes was AA(9.7%), AG(25.7%), GG(64.6%) in HCC patients, AA(6.2%), AG(41.6%), GG(52.2%) in healthy controls. There was a significant difference for distribution frequency of IGF-2R genotypes between the patients and healthy controls(χ2=6.637, P=0.036). When compared with wild-type GG genotype, the result showed that HCC patients with mutated AG heterozygous had a decreased risk for developing hepatocellular carcinoma(OR=0.499,95%CI:0.280～0.887). There was no significant difference in the allele frequency distribution between HCC patients and healthy controls(χ2=3.549, P=0.06).(3), The distribution frequency for IGF-1R (G1013A) genetypes was AA(8.0%), AG(49.5%), GG(42.5%) in HCC patients, AA(9.7%), AG(51.4%), GG(38.9%) in healthy controls. There was no significant difference for distribution frequency of IGF-1R (G1013A) genotypes between cases and controls (χ2=0.409, P=0.815). There was no significant difference in the allele frequency distribution between cases and controls (χ2=0.293, P=0.588).(4), There was no mutation in SNP locus rs61740868of IGF-1R gene in both the cases and controls. There was no significant difference for distribution frequency of IGF-1R (rs61740868) genotypes between the patients and healthy controls (P>0.05).4. Gene-environmental exposure factors interactionThere were no significant difference in the combination of gene and environmental factors between HCC patients and healthy controls by the multiplication model of crossover analysis and logistic regressionP>0.05).(1), When compared with the combination of IGFs wild-type genotype and no exposure of cigarette smoking, the combination of IGF-2GG/AG genotype and cigarette smoking showed an increased risk for developing hepatocellular carcinoma(OR=1.967,95%CI:0.668～5.791); the combination of IGF-2R AA/AG genotype and cigarette smoking showed an decreased risk for developing hepatocellular carcinoma(OR=0.961,95%CI:0.466～1.981); the combination of IGF-1R AA/AG genotype and cigarette smoking showed an increased risk for developing hepatocellular carcinoma(OR=1.323,95%CI:0.629～2.780), however, there was no statistically difference(P>0.05).(2), When compared with the combination of IGFs wild-type genotype and no exposure of alcohol consumption, the combination of IGF-2GG/AG genotype and alcohol consumption showed an increased risk for developing hepatocellular carcinoma(OR=2.942,95%CI:0.858～10.085); the combination of IGF-2R AA/AG genotype and alcohol consumption showed an increased risk for developing hepatocellular carcinoma(OR=1.322,95%CI:0.635～2.754); the combination of IGF-1R AA/AG genotype and alcohol consumption showed an increased risk for developing hepatocellular carcinoma(OR=1.805,95%CI:0.816～3.922), however, there was no statistically difference(P>0.05).(3), When compared with the combination of IGFs wild-type genotype and no exposure of infection of HBsAg, the combination of IGF-2GG/AG genotype and detection of HBsAg showed an increased risk for developing hepatocellular carcinoma(OR=20.086,95%CI:3.243～209.824); the combination of IGF-2R AA/AG genotype and HBsAg positive showed an increased risk for developing hepatocellular carcinoma(OR=7.312,95%CI:2.983～17.928); the combination of IGF-IR AA/AG genotype and HBsAg positive showed an increased risk for developing hepatocellular carcinoma(OR=11.551,95%CI:4.307～30.983), however, there was no statistically difference(P>0.05).5Gene-gene interactionThere were no significant difference in the combination of gene and gene in insulin-like growth factors between HCC patients and healthy controls by the multiplication model of crossover analysis and logistic regression(P>0.05).Conclusion:IGF-2R genetic polymorphisms could be considered as one of the most important factors contributing to increased susceptibility and development of hepatocellular carcinoma. However, IGF-2and IGF-IR may not be risk factors for the development of hepatocellular carcinoma. Alcohol consumption and infection of HBsAg may be risk factors for hepatocellular carcinoma.There were no evidence in the interaction of gene-environmental and gene-gene between HCC patients and healthy controls. |
PDF Full Text Request