The Research Of Genetic Susceptibility Of The Protein Expression And Gene Polymorphism Of The NQO1 With Family Gathered Hepatocellular Carcinoma

Objective:(1)To explore the protein expression of NQO1 in family gathered hepatocellular carcinoma and to discusses the relationship with clinical pathologic. (2) To explore the relationship between the protein expression of NQO1 and the gene polymorphism of NQO1 and the genetic susceptibility of family gathered hepatocellular carcinoma.Materials and methods:(1)Using immunohistochemistry S-P method to detect 32 cases of benign liver tissue disease(control group), 41 cases of non-family gathered hepatocellular carcinoma (non-family liver cancer) tissue and tissue adjacent to carcinoma, the situation of NQO1 protein expression in 34 cases of family gathered hepatocellular carcinoma (family liver cancer) tissue and tissue adjacent to carcinoma. And analysing the relationship between NQO1 protein expression and hepatocellular carcinoma of clinical pathological factors. (2)Using polymerase chain reaction-restriction fragment length polymorphism( PCR– RFLP) technic detected 32 cases of benign liver tissue disease, 41 cases of non-family gathered hepatocellular carcinoma tissue, the genotypes of three common polymorphism sites (rs1800566, rs4986998,rs10517) in NQO1 gene of 34 cases of family gathered hepatocellular carcinoma tissue. (3) With the method of sequencing verification to detect DNA genotype.Results: NQO1 proteins are expressed in hepatocellular carcinoma tissue and normal liver tissue.(1) The NQO1 protein expressions of the carcinoma tissue in Family hepatocellular carcinoma group and in non- family hepatocellular carcinoma group are lower than that of normal group, Each comparative differences have statistically significant (P < 0.05).(2) The NQO1 protein expression of family hepatocellular carcinoma group is lower than non-family hepatocellular carcinoma group,Two groups of comparisons difference was statistically significant (P < 0.05).(3) The NQO1 protein expression of Family hepatocellular carcinoma tissue group is significant lower than tissue adjacent to carcinoma, Two groups of comparisons difference was statistically significant (P < 0.05).(4) The NQO1 protein expression of non-family hepatocellular carcinoma tissue also obviously lower than tissue adjacent to carcinoma, Two groups of comparisons difference was statistically significant (P < 0.05).(5) The NQO1 protein expression of Family hepatocellular carcinoma group, non-family hepatocellular carcinoma group's tissue adjacent to carcinoma are below normal liver tissue, Two groups of comparisons difference was statistically significant (P < 0.05).(6) The NQO1 protein expression of Family hepatocellular carcinoma group is lower than non-family hepatocellular carcinoma group, Two groups of comparisons difference was statistically significant (P < 0.05).(7) The NQO1 protein expression of Family gathered hepatocellular carcinoma group is irrelevant with age,sex,HBsAg,pathologic stage, But it is relevant with AFP quantitative, tumor size and the number of suffering carcinoma in family member.(8) Rs1800566 site T/T genotype frequency, Family hepatocellular carcinoma group (52.9 %) significantly higher than non-family hepatocellular carcinoma group (29.3%) and the normal group (21.9%), Each comparative differences have statistically significant (P = 0.037, P = 0.009 < 0.05). And because the more number of suffering carcinoma in family member, the higher frequency of T/T genotype, Comparative differences have statistically significant (P = 0.011 < 0.05) . Hepatocellular carcinoma patients carry T/T genotype, its family members of hepatocellular carcinoma risk is 2.719 times than who carry C/C genotype (95% CI: 1.049 ~ 7.043).(9) Rs4986998 site in the frequency of each genotypes mainly behaves as C/C wild homozygous type, by way of Hardy-Weinbery genetic balance test, it doesn't accord with balance law (x2 = 61.818, P = 0.000 < 0.05), indicate that the polymorphism research of samples in this site are non-representative. (10)The frequency of Rs10517 site C/T genotype , family hepatocellular carcinoma group (44.1%) and non-family hepatocellular carcinoma group (48.8%)obviously lower than that of normal group(78.1%) (P = 0.005, P = 0.011 < 0.05), Comparative differences have statistically significant.Conclusion: (1) The differences in NQO1 protein expression may play a role in the origin and development of family gathered hepatocellular carcinoma.(2) The NQO1 genes is relevent with family gathered hepatocellular carcinoma, rs1800566 site T/T genotypes of NQO1 gene may is the genetic susceptibility genes of the phenomenon of the family gathered hepatocellular carcinoma.(3) Rs10517 site C/T genotype of NQO1 gene is relevent with hepatocellular carcinoma, may be one of the risk factors to cause hepatocellular carcinoma .