A Study Of Chromosomal Aberration And Genetic Susceptibilitin Familial Clustering Hepatocellular Carcinoma

Objective : The devolopment of hepatocellular carcinoma (HCC) has an intensive trendency of clustering in certain families, yet this trendency far from being fully elucidated . To screen the genetic susceptible gene and to evaluate its role in patients with HCC familial history , the chromosomal imbalance aberration and metablic enzyme gene polymorphisms were investgated in familial clustering HCC . Methods: 15 cases of familial clustering HCC and 10 cases of none familial clustering HCC specimen obtained from surgical resection were used to detect the aberration of chromosome by comparative genomic hybridization (CGH) . Furthermore , the CYP2D6 , CYP2E1 ,GSTM1, GSTT1 gene polymorphism and HBx gene, P53gene were also deteced by PCR or PCR-RFLP and DNA sequencing in 80 cases of familial clustering HCC and 130 cases of none familial clustering HCC . Results: The aberration was found in 25 cases of HCC , the gain were commonly deteced on chromosome 1q (72.0%), 1p(64.0%), 2p(48.%), 2q(48.0%), 5q(48.0%), 7q(44.0%), the loss were often found on chromosome 4q(48.0%), 16p(48.0%), 8p(40.0%), 17p(36.0%) ; For majority chromosomal regions , There was no significant difference of the aberration rate show between familial clustering HCC and none familial clustering HCC, except for +17p,+18p , which is distinctivefeature of familial clustering HCC. The frequencies of CYP2D6 non-T/T(C/C and C/T combined) genotype and CYP2E1 non-Cl/Cl (C1/C2 and C2/C2 combined ) genotpye were 66.7% and 52.0% in familial clustering HCC group ,which were significantly higher than that of control group (48.0%, 30.7% respectively), there were no statistical difference when compare with none familial clustering HCC group (73.4% , 42.6% respectively). The frequencies of GSTMl null and GSTTl null genotype were 68.8% and 47.5% in familial clustering HCC group, which were significantly higher than none familial clustering HCC group (54.6% , 30.8% respectively) and control group (53.3% , 25.3% respectively). The same trendency was also found between high-incidence pedigrees of HCC and control pedigrees . With the increasing numbers of HCC patient in familial history , the frequencies of GSTMl null and GSTTl null genotype increased too ; The familial risk of HCC increase among barriers of both GSTMl null and GSTTl null genotype . The P53 gene codon 249 mutation rate in familial clustering HCC group (53.8%) was significantly higher than that of none familial clustering HCC group (36.2%), With the increasing numbers of HCC patient in familial history , the mutation rate of P53 gene increased too . No significant difference of HBx gene postive rate was found when comparing familial clustering HCCgroup with none familial clustering HCC group either in tumor tissue or in non-tumor tissue, but postive rate of HBx gene in this two groups were significantly higher than that of control group. Conclusion: (1) The gain of 17p, 18p is the distinctive feature of familial...