Association between single nucleotide polymorphisms (SNPs)of IL-6, TNF-alpha and VEGF-A genes, and susceptibility tohepatocellular carcinoma (HCC)

Giuseppe Montalto, Maurizio Soresi, Lydia Giannitrapani, Luigi Rizzuto, Antonio Mario Giacalone, Salvatore Marasa'

Risultato della ricerca: Other contribution

Abstract

Background: Many studies have demonstrated the association between SNPs and susceptibilityto the development of diseases such as autoimmune diseases and neoplasms. These allelicvariations may involve regulatory and coding regions of cytokine genes and may influence theirtranscriptional activity and, as a consequence, their protein levels. Hepatocarcinogenesis is amulti-step and multi-factorial process in which both environmental and genetic factors areinvolved. Liver cirrhosis (LC) of both HBV or HCV origin is considered the most important riskfactors for HCC.Objectives: We evaluated the frequency of genetic polymorphisms of the cytokines IL-6 and TNFalphaand of VEGF-A in a group of patients with HCC(n=112) and underlying LC and comparedthem with a group of cirrhotic patients (n=90), without HCC, and a group of age- and sex-matchedcontrols(n=124) in order to verify an eventual correlation between the allelic variations and the riskof developing tumor.Methods: DNA extracted from whole blood of the three Sicilian groups, was used for theevaluation of SNPs using Restriction Fragment Length Polymorphisms (RFLP) method in -174position of IL-6 gene promoter (G/C transversion, G allele is associated with higher levels of thecytokine); -308 position of TNF-alpha gene promoter (G/A transition, G allele is associated withlower levels of the cytokine); 936 position of the coding region of VEGF-A gene (G/T transition,T allele is associated with high levels of VEGF-A). Data were analyzed was performed using thechi square and the Fisher exact tests were appropriated. P value was considered significant if<0.05. Results: Genotype frequency of IL-6 -174 was: controls vs HCC p < 0.79, controls vs cirrhosisp < 0.24, HCC vs controls p < 0.22; genotype frequency of TNF-alpha -308 was: controls vs HCCp < 0.057, controls vs cirrhosis p < 0.44, HCC vs controls p < 0.06; genotype frequency ofVEGF-A 936 was: controls vs HCC p < 0.21, controls vs cirrhosis p < 0.22, HCC vs controls p< 0.60.Conclusion: These results do not demonstrate a significant correlation between the allelicvariants considered and the risk of developing HCC. However the trend almost statisticallysignificant of SNP -308 of TNF-alpha may suggest that in HCC subjects there are more A carrierswith a higher susceptibility to the inflammatory type which may contribute to the developmentof the tumor.
Lingua originaleEnglish
Stato di pubblicazionePublished - 2009

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