| Objective: We screened patients with HBV-related HCC from JiangXi region with Phosphatase and tensin homology deleted on cnhromosome 10 gene (PTEN) as a candidate gene to explore the association of PTEN gene with HBV-related HCC and clinical phenotypes.Methods: 60 patients with HBV-related HCC, 70 patients with Chronic Viral Hepatitis B (CH-B) and 135 normal controls(C) were collected. Candidate gene and direct DNA sequencing were used for screening the exons and introns of PTEN to search for the mutations and analysis the correlation of porlymorphisms and HCC. Hardy-Weinberg equilibrium, frequencies comparison of genotype , allele and haplotype between each group were calculated byχ~2 test or Fisher's exact test and relative risk were calculated by unconditional logistic regression analysis.Results: No PTEN gene mutation was found in all HCC patients,except four polymorphisms: Ala34Cys,leu57phe,IVS8+G32T and T2281G.We selected the common polymorphisms- Ala34Cys and IVS8+G32T (Frequency>5%) which might affect the expression of PTEN to research.The results of genotyping showed that two kinds of genotypes GC/GC and GC/TG were detected with, three genotypes G/G, G/T, T/T with IVS8+G32T, and TG/TG was not found with Ala34Cys polymorphism.There were no statistically difference of genotypes and allele frequency distributions among HCC group,CH-B groups and normal controls. On Ala34Cys and IVS8 + G32T for haplotype construction,we are found four haplotypes: GCG, GCT, TGT, TGG.χ2 test showed that compared with the normal control group, GCG haplotype distribution were significantly different in HCC group (χ2 = 4.78, P = 0.03), logistic regression analysis showed that haplotype GCG carriers compared with non-carriers significantly reduced the risk of HCC (OR = 0.62,95% CI:0.40-0.95), the other 3 haplotypes were not found significant difference. Further analysis showed that there were no significant differences between the genotype ,allele and haplotype frequency distributions in HBV-related HCC clinicopathological parameters including serum alpha-fetoprotein (AFP), cirrhosis, tumor grade, number, size, TNM stage. However, compared with GC/TG and the G allele, Ala34Cys GC/GC genotype and IV8+G32T T allele had higher proportion in the AFP≥400 ug/L group ( respectively,70.2% vs 29.8% and 55.3% vs 44.7%), cirrhosis group ( respectively,77.8% vs 22.2% and 55.6% vs 44.4%), poorly differentiation group ( respectively,78.6% vs 21.4% and 60.7% vs 39.3%), tumor diamete≥5cm group ( respectively,71.8% vs 28.2% and 57.7% vs 42.3%), multiple tumor group ( respectively,79.2% vs 20.8% and 61.4% vs 38.6%), TNM stage III+IV group ( respectively,70.0% vs 30.0% and 60.0% vs 40.0%) and metabasis group ( respectively,82.4% vs 17.6% and 55.8% vs 44.2%).Conclusion: 1.We found 4 polymorphisms Ala34Cys,leu57phe,IV8+G32T and T2281G, in which Ala34Cys, leu57phe and T2281G for the first time.2.There may be an interaction between PTEN Ala34Cys and IV8+G32T polymorphisms with the development of HBV related hepatocellular carcinoma in Jiangxi population., carrying GCG haplotype have protective effects for the occurrence of HBV-related hepatocellular carcinoma.3. These results demonstrated that PTEN gene mutation wasn't related with HBV-related hepatocellular carcinoma from jiangxi region. |
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