- Email: [email protected]
598 THE INCIDENCE OF HEPATOCELLULAR CARCINOMA ASSOCIATED WITH HEPATITIS C INFECTION DECREASED IN KYUSHU, JAPAN
POSTERS Conclusions: One out of four CEUS examinations in our Hepatoogy Unit gave a definitive diagnosis, mainly in cases of benign lesions and PVT. In this patients no need for referral to other units was required. CEUS examination turned to be completely useless in up to 20% cases. 598 THE INCIDENCE OF HEPATOCELLULAR CARCINOMA ASSOCIATED WITH HEPATITIS C INFECTION DECREASED IN KYUSHU, JAPAN N. Taura1,2 , H. Yatsuhashi1 , K. Nakao2 , M. Sata3 , The Liver Cancer Study Group of Kyushu. 1 Clinical Research Center, National Nagasaki Medical Center, Omura, 2 Department of Gastroenterology and Hepatology, Graduate School of Biomedical Sciences Nagasaki University, Nagasaki, 3 Graduate School of Medical and Dental Sciences, Division of Gastroenterology, Kurume University School of Medicine, Kurume, Japan E-mail: [email protected] Background: The incidence of hepatocellular carcinoma (HCC) in Japan has still been increasing. The aim of the present study was to analyze the epidemiological trend of HCC in the western area of Japan, Kyushu. Method: A total of 10,010 patients with HCC diagnosed between 1996 and 2008 in the Liver Cancer study group of Kyushu (LCSK), were recruited for this study. Cohorts of patients with HCC were categorized into five year intervals. The etiology of HCC was categorized to four groups as follows; B: HBsAg positive, HCVRNA negative, C: HCV-RNA positive, HBsAg negative, B+C: both of HBsAg and HCV-RNA positive, nonBC: both of HBsAg and HCV-RNA negative. Results: B was 14.8% (1,485 of 10,010), whereas 68.1% (6,819 of 10,010) had C, and 1.4% (140 of 10,010) had HCC associated with both viruses. The remaining 1,566 patients (15.6%) did not associate with both viruses. Cohorts of patients with HCC were divided into six-year intervals (1996–2001 and 2002–2007). The ratio of C cases decreased from 73.1% in 1996–2001 to 64.9% in 2002–2007. On the other hand, B and -nonBC cases increased significantly from 13.9% and 11.3% in 1996–2001 to 16.2% and 17.6% in 2002–2007, respectively. Conclusion: The incidence of hepatocellular carcinoma associated with hepatitis C infection decreased after 2001 in Kyushu area. This change was due to the increase in the number and proportion of the HCC not only nonBC patients but also B patients. 599 ALLELES AND GENOTYPES OF IL-18 AND TNF-a PROMOTER POLYMORPHISMS ARE ASSOCIATED WITH HIGHER RISK OF HEPATOCELLULAR CARCINOMA (HCC) IN BRAZILIAN POPULATION 2 A.C. Teixeira1 , C.T. Mendes-Junior ´ , F.F. Souza1 , C.A.B. Cant˜ao3 , 1 1 S.C. Ferreira , N.H.S. Deghaid , E.C. Castelli1 , E.D. Mente3 , A.K. Sankarankutty3 , S. Zucoloto4 , J. Elias Jr.1 , V. Muglia1 , O. Castro-Silva3 , E.A. Donadi1 , A.C. Martinelli1 . 1 Medicine, School of Medicine of Ribeir˜ ao Preto, University of S˜ ao Paulo, 2 Chemistry, University of S˜ ao Paulo, 3 Surgery and Anatomy, School of Medicine of Ribeir˜ ao Preto, University of S˜ ao Paulo School of Medicine, 4 Pathology, School of Medicine of Ribeir˜ ao Preto, University of S˜ ao Paulo, Ribeir˜ ao Preto, Brazil E-mail: [email protected] Background and Aims: There is increasing evidence regarding the association between cytokine genes polymorphisms and carcinogenesis including hepatocellular carcinoma (HCC). However, few data is available in HCC low-risk populations. We evaluated the association of polymorphisms at tumor necrosis factor-a (TNF-a), interleukin-18 (Il-18) and interferon gamma (IFNg) genes with the risk of HCC. S236
Methods: The study included 112 patients with HCC followed at the University Hospital, Faculty of Medicine of Ribeir˜ao Preto, S˜ao Paulo, Brazil, and 202 healthy controls from the same geographic area. We amplified five Single Nucleotide Polymorphisms (SNPs) spread across the TNF-a (−238G/A and −308G/A), IL-18 (−137G/C and −607C/A), and IFNg (+874T/A) genes by Polymerase Chain Reaction (PCR). PCR products were submitted to polyacrilamide gel electrophoresis and visualized by silver staining. Results: A significant association was found between HCC and the following polymorphisms: TNF-a −238*A allele [P = 0.003; odds ratio (OR) = 2.12, 95% confidence interval (CI): 1.32 to 3.40], TNF-a −308*A allele (P = 0.035; OR = 1.82, 95% CI: 1.07 to 3.08) and IL-18 −607*A allele (P = 0.024; OR = 1.49, 95% CI: 1.06 a 2.09). On the other hand, IL-18 −137G/C and IFNg +874T/A did not associate with HCC. When genotypes were evaluated, TNFa −238GA (P = 0.001; OR = 2.45, 95% CI: 1.46 to 4.12), TNFa −308GA (P = 0.003; OR = 2.51, 95% CI: 1.40 to 4.51) and IL-18 −607AA (P = 0.005; OR = 3.03, 95% CI: 1.40 to 6.56) genotypes were significantly associated with susceptibility to HCC. Conclusion: Our results suggest that TNF-a (−238G/A and −308G/A) and IL-18 −607C/A SNPs may confer susceptibilities to the development of HCC, with TNF-a −238*A, −308*A and IL-18 −607*A alleles playing a role as risk factors. 600 THE 14BP-DELETION POLYMORPHISM IN HLA-G GENE CONFERS SUSCEPTIBILITY TO THE DEVELOPMENT OF HEPATOCELLULAR CARCINOMA (HCC) IN BRAZILIAN POPULATION A.C. Teixeira1 , E. Castelli1 , F. Souza1 , C. Cant˜ao1 , S. Ferreira1 , C. Mendes-Junior2 , N. Deghaide1 , E. Mente3 , A. Sankarankutty3 , S. Zucoloto4 , L. Ramalho4 , J. Crispim1 , O. Castro-e-Silva3 , E. Donadi1 , A.L.C. Martinelli1 . 1 Medicine, School of Medicine of Ribeir˜ ao Preto, University of S˜ ao Paulo, 2 Chemistry, University of S˜ ao Paulo, 3 Surgery and Anatomy, School of Medicine of Ribeir˜ ao Preto, University of S˜ ao Paulo School of Medicine, 4 Pathology, School of Medicine of Ribeir˜ ao Preto, University of S˜ ao Paulo, Ribeir˜ ao Preto, Brazil E-mail: [email protected] Background and Aims: Human leukocyte antigen-G (HLA-G) is a non-classical HLA class I molecule involved in tumor escape mechanisms. Considering that the HLA-G 14 bp insertion/deletion polymorphism is located at the 3 UTR in exon 8, and since it has been associated with the magnitude of HLA-G production, in the present study we evaluated the association of 14bp insertion/deletion polymorphism with the risk of developing HCC. Methods: A total of 85 HCC patients followed at the University Hospital, Faculty of Medicine of Ribeir˜ao Preto, S˜ao Paulo, Brazil, and 202 healthy controls from the same geographic area were typed for the 14bp insertion/deletion polymorphism using PCR-amplified DNA hybridized with specific primers. Results: Compared to controls, the frequency of the 14 bp insertion allele was underrepresented (44% versus 31%, respectively, P = 0.005) and the 14bp deletion overrepresented in HCC patients (56% versus 69%, respectively, P = 0.005). The 14 bp deletion conferred an odds ratio (OR) = 1.72; 95% confidence interval (CI): 1.18 to 2.52. Similarly, the deletion/deletion genotype was overrepresented in HCC patients (51% versus 35% in controls, P = 0.025), conferring an OR = 1.84 (95% CI: 1.11 to 3.07). The frequencies of the deletion/insertion or insertion/insertion genotypes observed in HCC patients were not different from those observed in controls (P > 0.05). Conclusion: Although many post-transcriptional factors may influence the magnitude of HLA-G mRNA production, including microRNAs, the 14bp deletion has been associated with increased amount mRNA production, which in turn may down-regulate host immune response, facilitating tumor cell escape of immunosurveillance.
Journal of Hepatology 2010 vol. 52 | S183–S317
Methods: The study included 112 patients with HCC followed at the University Hospital, Faculty of Medicine of Ribeir˜ao Preto, S˜ao Paulo, Brazil, and 202 healthy controls from the same geographic area. We amplified five Single Nucleotide Polymorphisms (SNPs) spread across the TNF-a (−238G/A and −308G/A), IL-18 (−137G/C and −607C/A), and IFNg (+874T/A) genes by Polymerase Chain Reaction (PCR). PCR products were submitted to polyacrilamide gel electrophoresis and visualized by silver staining. Results: A significant association was found between HCC and the following polymorphisms: TNF-a −238*A allele [P = 0.003; odds ratio (OR) = 2.12, 95% confidence interval (CI): 1.32 to 3.40], TNF-a −308*A allele (P = 0.035; OR = 1.82, 95% CI: 1.07 to 3.08) and IL-18 −607*A allele (P = 0.024; OR = 1.49, 95% CI: 1.06 a 2.09). On the other hand, IL-18 −137G/C and IFNg +874T/A did not associate with HCC. When genotypes were evaluated, TNFa −238GA (P = 0.001; OR = 2.45, 95% CI: 1.46 to 4.12), TNFa −308GA (P = 0.003; OR = 2.51, 95% CI: 1.40 to 4.51) and IL-18 −607AA (P = 0.005; OR = 3.03, 95% CI: 1.40 to 6.56) genotypes were significantly associated with susceptibility to HCC. Conclusion: Our results suggest that TNF-a (−238G/A and −308G/A) and IL-18 −607C/A SNPs may confer susceptibilities to the development of HCC, with TNF-a −238*A, −308*A and IL-18 −607*A alleles playing a role as risk factors. 600 THE 14BP-DELETION POLYMORPHISM IN HLA-G GENE CONFERS SUSCEPTIBILITY TO THE DEVELOPMENT OF HEPATOCELLULAR CARCINOMA (HCC) IN BRAZILIAN POPULATION A.C. Teixeira1 , E. Castelli1 , F. Souza1 , C. Cant˜ao1 , S. Ferreira1 , C. Mendes-Junior2 , N. Deghaide1 , E. Mente3 , A. Sankarankutty3 , S. Zucoloto4 , L. Ramalho4 , J. Crispim1 , O. Castro-e-Silva3 , E. Donadi1 , A.L.C. Martinelli1 . 1 Medicine, School of Medicine of Ribeir˜ ao Preto, University of S˜ ao Paulo, 2 Chemistry, University of S˜ ao Paulo, 3 Surgery and Anatomy, School of Medicine of Ribeir˜ ao Preto, University of S˜ ao Paulo School of Medicine, 4 Pathology, School of Medicine of Ribeir˜ ao Preto, University of S˜ ao Paulo, Ribeir˜ ao Preto, Brazil E-mail: [email protected] Background and Aims: Human leukocyte antigen-G (HLA-G) is a non-classical HLA class I molecule involved in tumor escape mechanisms. Considering that the HLA-G 14 bp insertion/deletion polymorphism is located at the 3 UTR in exon 8, and since it has been associated with the magnitude of HLA-G production, in the present study we evaluated the association of 14bp insertion/deletion polymorphism with the risk of developing HCC. Methods: A total of 85 HCC patients followed at the University Hospital, Faculty of Medicine of Ribeir˜ao Preto, S˜ao Paulo, Brazil, and 202 healthy controls from the same geographic area were typed for the 14bp insertion/deletion polymorphism using PCR-amplified DNA hybridized with specific primers. Results: Compared to controls, the frequency of the 14 bp insertion allele was underrepresented (44% versus 31%, respectively, P = 0.005) and the 14bp deletion overrepresented in HCC patients (56% versus 69%, respectively, P = 0.005). The 14 bp deletion conferred an odds ratio (OR) = 1.72; 95% confidence interval (CI): 1.18 to 2.52. Similarly, the deletion/deletion genotype was overrepresented in HCC patients (51% versus 35% in controls, P = 0.025), conferring an OR = 1.84 (95% CI: 1.11 to 3.07). The frequencies of the deletion/insertion or insertion/insertion genotypes observed in HCC patients were not different from those observed in controls (P > 0.05). Conclusion: Although many post-transcriptional factors may influence the magnitude of HLA-G mRNA production, including microRNAs, the 14bp deletion has been associated with increased amount mRNA production, which in turn may down-regulate host immune response, facilitating tumor cell escape of immunosurveillance.
Journal of Hepatology 2010 vol. 52 | S183–S317