| Objectives To explore the distribution frequency and characteristics of three common single-nucleotide polymorphisms (SNPs)of interleukin 6 (IL - 6) and interleukin 10 (IL - 10) gene promoter of people in GuangXi area , the relationship between genotypes of IL-6-572, IL -10-819,IL-10-592 and the risk of chronic hepatitis B virus (HBV) infection or hepatocellular carcinoma (HCC) . This study also approach the interaction between the genotypes and cancer family history, smoking, alcohol consumption ,and genes and gene occurred in HCC , aiming at understanding of pathogenesis of HCC, looking for individual susceptibility of molecular markers, and providing the reference for prevention of HCC.Methods The research was designed as a case-control study based on hospital. From June 2007 to June 2010, newly histopathologically diagnosed HCC patients from the First Affiliated Hospital of Guangxi Medical University , Affiliated Tumor Hospital of Guangxi Medical University ,LIUZHOU people's hospital , and the First Affiliated Hospital of Guangxi Traditional Chinese Medicine University were recruited as the case group. HBV carriers From the above hospitals were enrolled as the same diagnosis and treatment of the 2000 standards on the 10th national viral hepatitis xi'an conference formulated by viral hepatitis prevention plan "(try the line) standard. Controls of non-cancer patients in the Spinal Orthopedic Department, Traumatic Department and Ophtalmology Department in the same hospitals, were recruited as the control group, with the case and the control matched in terms of ages, sex, and habitation. All the subjects had signed the study consensus protocol . And all the subjects were surveyed face to face by the specifically trained investigators. The questionaire features include basic datum, disease history, personal history, family history, smoking history, and drinking history etc. 2ml fasting venous blood were collected at the second day morning, and genome DNA were extracted at the same day. 3 common SNP loci of IL-6 and IL-10 genes were measured with high flux TaqMan MGB, a fluorescent quantitative real time PCR method. All data were input and analyzed statistically in SPSS 13.0 for Windows. Student's t-test was used to compare mean value of the samples. While categorical data were compared with the use of the chi-square test or the Fisher's exact propability. Odd ratio and 95% confidence interval indicate relative risk scale, and they were analyzed with the non-conditional logistic regress model.Results1. The subjects demographic data showed: A total of 1080 subjects with complete information were recruited, with 381 for patients, 340 for HBV carriers , and 359 for healthy controls. The distribution difference in age, sex, nationality, marital and professional aspects were not significant in three group (P > 0.05). The distribution frequency of smoking, drinking and family history were significantly different in the three groups (P < 0.05).2. genotypes, allele frequency distribution of IL - 6 and IL - 10(1) The genotype frequencies of IL-6-572 CC,CG,GG were 67.98%,28.87%,3.15% in the cases;61.76%,31.48%,6.76% in carriers with HBV;67.13%,29.25%,3.62% in the controls respectively , the differences were not significant in the three groups (P > 0.05). differences of the allele mutation frequencies of IL-6-572C/G were significant in the three groups (P < 0.05).(2) The genotype frequencies of IL-10-819CC,CT,TT were 44.62%,41.47%,13.91% in the cases;54.12%,36.47%,9.41% in carriers with HBV;50.42%,39.83%,9.75% in the controls respectively , the differences were not significant in the three groups (P > 0.05).The allele mutation frequencies of IL-10-819C/T significances were shown in the three groups (P < 0.05).(3) The genotype frequencies of IL-10-592CC,CA,AA were 46.98%,45.15%,7.87%;50.29%,39.71%,10.00%;50.14%,40.11%,9.75%;in the three groups respectively,and there were no significant difference in the groups (P > 0.05) . there were no significant difference in the allele mutation frequencies of IL-10-592 C/A in the groups (P > 0.05) .3.The relationship between IL– 6, IL - 10 gene SNPs and chronic HBVinfection riskCompared with the CC genotypes on IL - 6-572 site, GG genotype increased the risk of chronic HBV infection (OR = 2.171, 95% CI: 1.068 ~ 4.415), GC genotypes had no association with chronic HBV infection (OR = 1.245, 95% CI: 0.894 ~ 1.735). IL - 10-819 site TT, TC genotype and IL - 10-592 site CC, CA genotypes had no significant correlations of individual risk of chronic HBV infection , showing in table 3.4.The relationship between IL– 6, IL - 10 gene SNPs and risk of HCCIL-6-572GG genotype is not associated with the risk of HCC(OR=0.981,95%CI:0.407～2.363). Compared with IL-10-819CC genotype ,the TT genotype increase the risk of HCC (OR=2.791,95%CI:1.326～5.874),and the CT genotype had no significant association with the risk of HCC(OR=1.090,95%CI:0.696～1.708). Compared with IL-10-592CC genotype , the AA genotype could decrease the risk of HCC in healthy people(OR=0.023, 95%CI:0.175～0.880),but AC genotype had no significant association with the risk of HCC(OR=1.142,95%CI:0.733～1.780). IL-10-819TT was the significant risk factor of HCC for HBV carriers(OR=3.522,95%CI:1.707～7.266),but not CT genotype(OR=1.439,95%CI:0.925～2.241) . For IL-10-592 loci ,the risk of HCC with AA genotype was decreased in HBV carriers(OR=0.336,95%CI:0.154～0.734).Conclusions1. IL-6-572 site G mutation alleles were the risk factor of chronic HBV infection of people in region of guangxi, and GG genotype increased the risk of individual chronic HBV infection . IL-10-819 loci genotype TT increased the risk of HCC , but AA genotypes of IL-10-592 sites might decrease the risk of HCCof people in region of guangxi, including health individual and HBV carriers.2. Interaction analysis of gene polymorphism and environment factors showed that interactions of IL - 6-572, IL - 10-819, IL - 10-592 SNPs and the risk factors of HCC, such as smoking and drinking existed .When concurrent with exposure to smoking or drinking , somebody with the mutation genotypes might significantly increased the risk of HCC, compared with any risk factor alone. interactions of IL - 6-572 SNP and the risk factors of HCC, such as smoking and drinking existed . When concurrent with exposure to smoking or drinking , somebody with the mutation genotypes might significantly increased the risk of HBV infection .
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