| Objective:Modern medicine is generally believed that cancer occurrence and development was a complex process, including genetic factors,environmental factors and their interaction. PNPLA3 encodes a transmembrane protein expressed in liver cell membrane, regulating lipid metabolism and inflammatory.Research found that PNPLA3 is associated with liver inflammation, hepatic fibrosis progression,the function of rs738409 has been taken seriously. TM6SF2 is responsible for metabolising of the liver lipid and encoding a transmembrane protein.the study found that the gene is related to liver fibrosis and fibrosis.Now researches about the relationship between PNPLA3,TM6SF2 with HCC are rarely. so about genetic factor we choose two genes PNPLA3rs738409, TM6SF2rs58542926 locis.As we all known that smoking and alcohol drinking are risk factors for many diseases, espically liver disease, so this study we choose smoking, alcohol drinking as environmental factors. Analysis the association between genetic factors and environmental factors with HBV- HCC, as well as different ending of chronic hepatitis B virus infection, and discusses the interaction between gene-gene,gene-environment.Methods:1 Candidate genes. Use NCBI search keywords: hepatocellular carcinoma, from the literature, selection of relevant English literature review after 2014 year,get relevant candidate genes PNPLA3, TM6SF2.The Hapmap project database(http://hapmap.ncbi.nlm.nih.gov /index. html.en) and Pubmed SNP PNPLA3 database retrieval, TM6SF2 gene loci information, people choose CHB(China Han Han crowd Chinese in Beijing, China). download them from the Hap Map database PNPLA3 gene SNP information into Haploview 4.2 software, using Haploview4.2 software was carried out on the site selection, choose the MAF(minimum allele frequency) > 10%, r2(linkage disequilibrium coefficient) > 0.8, D(the degree of linkage disequilibrium degree change with distance and) = 1 sites, as well as in Pubmed SNP database retrieval TM6SF2 gene locus information, combined with literature, finally selected PNPLA3rs738409 site and TM6SF2 rs 58542926 site.2 Sample collecting 2161 people were collected in shijiazhuang four 3 armour hospital, including Chronic hepatitis B patients(Chronic hepatitis B, CHB) 691 people, cirrhosis( Liver cirrhosis, LC), 680 patients with hepatitis B virus associated Liver cancer(hepatitis B virus get hepatocellular carcinoma, HBV- HCC) 420 people and 370 healthy subjects, at the same time, collecting study objects' baseline data and clinical examination results.3 Genes detecting Extracting DNA from peripheral blood, detecting of candidate genes PNPLA3, TM6SF2 two SNP loci(rs738409, rs58542926) polymorphism. PNPLA3 rs738409 gene polymorphisms were CC,CG, GG.TM6SF2rs58542926 gene polymorphisms were CC, CT, TT.4 Statistic method Epdidata3.1 software was used to establish database, Online SNP stats was used to looking for genetic polymorphisms of the optimal assignment model, SPSS20.0and SAS9.1were used to analysis of data. The goodness-of-fit test for Hardy- Weinberg test; The unconditioned Logistic regression analysis of disease related gene polymorphism and filtered smoking and drinking, use the logistic and additive model to analyze gene –gene.gene-environment interaction. ? =0.05,H-W E ? =0.10,logistic regression ?_? =0.05,?_? =0.10.Results: 1 general informationHealth group includes 205 male and 165 female; CHB group includes 466 male and 225 female; LC group includes 470 male and 210 female; HBV-HCC group includes 326 male and 94 female. According ?~2 test,?~2=45.223,P<0.001, four groups have statistically difference in the gender construction. CHB group and LC group have no statistical difference in 7gender construction(P=0.504), and other groups in gender composition have statistical difference. the composition of male has linear upward trend,(?~2= 42.910, P<0.001).Healthy group's age median was 47 years, interquartile range was 22 years old; CHB group' s age median was 39 years, interquartile range was 20 years. LC group's age median was 52 years, interquartile range was 14 years; HBV-HCC group's age median was 57.0 years, interquartile range was12 years. According ?~2 test, ?~2=491.55, P<0.001, four group's age have statistical difference. Compared with each other, LC group and HBV-HCC group have no statistical difference in age, the rest of groups have statistical difference in age. 2 H-W equilibrium testHealthy group rs738409,rs58542926 locis of genotype frequency distribution were accorded with Hardy-Weinberg equilibrium test,?~2_?? were1.402,1.546,both P>0.10.CHB group rs738409 genotype frequency distribution doesn't conform to the H–W equilibrium,???~2_?? = 11.980, P<0.005). In addition, other groups fit the H-W equilibrium test. 3 On-line model selection analysisLC + CHB with HBV-HCC group, rs58542926 select codominant model, CC = 1, CT = 2, TT = 3. rs738409 assignment according to the presence of mutations, CC = 0, CG/GG = 1. 4 Multinomial Logistic 4.1Compared with healthy group:CHB group: Age increased 1 year, P< 0.001, OR = 0.951, 95% CI(0.941, 0.961); Male compared with female, P< 0.001, OR = 1.679, 95% CI(1.241, 2.273). LC group: Age increased 1 year, P< 0.001, OR = 1.034, 95% CI(1.022, 1.045); Male compared with female, P < 0.001, OR = 2.278, 95% CI(1.684, 3.082). HBV- HCC group: Age increased 1 year, P < 0.001, OR = 1.076, 95% CI(1.062, 1.091); Male compared with female, P< 0.001, OR = 3.002, 95% CI(2.080, 4.331), rs58542926 has one mutation gene, P = 0.039, OR = 1.659, 95% CI(1.026, 2.684).CHB group as controlled group: LC group: Age increased 1 year, P < 0.001, OR = 1.087, 95% CI(1.076, 1.098); Male compared with female, P< 0.001, OR = 1.356, 95% CI(1.029, 1.789), rs738409 CG/GG, compared with CC, P = 0.020, OR = 0.751, 95% CI(0.589, 0.956). HBV- HCC group: Age increased 1 year, P< 0.001, OR = 1.132, 95% CI(1.117, 1.147); Male compared with female, P = 0.001, OR = 1.787, 95% CI(1.257, 2.542), drinking compared with not drinking, P = 0.012, OR = 1.680, 95% CI(1.121, 2.519).Compared with LC group,HBV- HCC group: Age increased 1 year, P< 0.001, OR = 1.041, 95% CI(1.029, 1.054); Alcohol drinking compared with not drinking, P = 0.020, OR = 1.539, 95% CI(1.071,2.213); Smoking compared with no smoking, P = 0.047, OR = 1.453, 95% CI(1.005, 2.099). 5 InteractionHBV-HCC group compared with health group, no interaction was found between gene-gene, gene-drinking,gene-smoking.LC + CHB compared with HBV-HCC group: interactions were found between rs738409 and rs58542926,fitting negative interactions additive model, P value was 0.017.Conclusions:1 In CHB?LC?HBV- HCC groups, male composition gradually increased, average age also increased.2 rs58542926 T mutation may be a risk factor of HBV- HCC, rs738409 G mutation may be a protect factor of LC. Alcohol drinking after HBV infection may be a risk factor for HBV-HCC,smoking and alcohol drinking may be risk factors for HBV-HCC after LC.3 After HBV infected,rs738409 and rs58542926 two locis contain mutation, may increase the occurrence of HBV-HCC?... |
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