Study On The Relationship Between HBV-related HCC And HBV Genotype, Pre-S/S Gene And Pre-C/C Gene Mutation In Guangdong Province Of China

Objective To Study the characteristics of HBV genotype, Pre-S/S gene and Pre-C/C gene mutation of HBV-related HCC in Guangdong Province of china, and to explore the relationship between them and the occurrence of HCC.Methods HBV DNA were extracted from sera derived 44 patients with HBV-related HCC and matched 43 asymptomatic carriers(ASC). pre-S/S gene and pre-C/C gene were amplified with PCR, positive products for gene sequencing and structural analysis.then to genotype and identify active mutation sites. Finaly, two sets of data were analyesd statistically.Results Subgenotype Ba were 21 cases(47.7%), subgenotype C1 were 19 cases(43.2%) and subgenotype C2 were 4 cases (9.1%)in HCC group.In the ASC group, subgenotype Ba were 19 cases (44.2%), subgenotyp Cl were 16 cases (37.2%), and subgenotyp C2 were 8 cases (18.6%), the distribution of subgenotypes was no significant difference between ASC group and HCC group. Compared with the ASC group, HCC group has a higher frequency of pre-S deletion mutation, pre-C mutation(G1899A), BCP mutation (A1762T/G1764A), C gene mutation (T1976A/C1977A), the difference were statistically significant (P value= 0.01,0.011,0.001,0.005). But the pre-C mutation (G1896A) between the two groups was no significant difference (P value= 0.506). Further sequencing analysis revealed that pre-S deletion mutation occurs mainly in the 3'terminus of pre-S1 region and the 5'terminus of pre-S2 region, and most of them were in-frame deleted. In HCC group,13 cases (61.9%)were coexisted with wild-type pre-S subgenomes,8 cases were only pre-S deletion mutation. Among all samples, Pre-S deletion mutation have no statistically significant between the subgenotypes Ba, C1, C2 (P= 0.919). In the HCC group, pre-S deletion mutation have also no statistically significant between subgenotypes Ba and C1 (P value= 0.726).Further analysis found that subgenotype C1 and C2 have a higher frequency of BCP mutation than subgenotype Ba in HCC group, BCP mutation have statistically significant between the subgenotypes Ba, C1, C2 in HCC group(P value= 0.049). The Logistic regression analysis found that HBV pre-S deletion mutation, BCP mutation(A1762T/G1764A), pre-C mutation (G1899A), C gene mutation (T1976A/C1977A) were associated with HCC (OR:7.045,95% CI:4.352-17.653 for pre-S deletion mutation; OR:9.524,95%CI:5.537-19.890 for BCP mutation; OR:3.875,95%CI:1.529-11.730 for pre-C mutation (G1899A); OR: 2.677,95%CI:1.598-6.954 for C gene mutation (T1976A/C1977A)).Conclusions Patients with HBV-related HCC have higher incidence of HBV pre-S deletion mutation, BCP mutation (A1762T/G1764A), pre-C mutation (G1899A), C gene mutation(T1976A/C1977A)in Guangdong Province of china, and the most subgenotypes were Ba and C1, these mutations may increase the risk of HCC.