RESUMEN
BACKGROUND: Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) remains one of the most common causes of poor long-term survival. However, the host genetic factors affecting increased risk of tumor recurrence after transplantation have not been thoroughly elucidated. The present study was designed to investigate the association of cytokine gene polymorphisms with the risk of tumor recurrence in LT patients for HCC. METHODS: Eleven single-nucleotide polymorphisms within the promoter regions of 7 cytokine genes, i.e., the IL-1 family (IL-1alpha and IL-1beta), IL-6, IL-8, IL-10, TNF-alpha, and TGF-beta1, were genotyped in 93 HCC patients treated with LT using DNA sequencing. The association between these polymorphisms and the risk of tumor recurrence was evaluated while controlling confounding clinical variables. RESULTS: The genotype frequency of IL-10 -1082 A/G in patients with and without recurrence of HCC was AA 83.3%, GA 16.7% and AA 97.6%, GA 2.4%, respectively. The association between IL-10 -1082 GA and recurrence was significant (P=0.033). No other single-nucleotide polymorphism in the cytokine gene was found to be associated with recurrence. Kaplan-Meier survival curves showed that the homozygous AA patients had a significantly longer mean recurrence-free survival than heterozygous GA patients (23.5 vs 5.7 months, P=0.001). However, multivariate analysis failed to reveal that the GA genotype of IL-10 -1082 A/G was an independent indicator of recurrence. CONCLUSIONS: This study suggests the lack of association of selected cytokine gene polymorphisms with HCC recurrence after LT in the Han Chinese population. The finding does not exclude the idea that other cytokine polymorphisms could act as candidate biomarkers of disease prognosis.
Asunto(s)
Carcinoma Hepatocelular/genética , Citocinas/genética , Neoplasias Hepáticas/genética , Trasplante de Hígado , Recurrencia Local de Neoplasia/genética , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/cirugía , Femenino , Predisposición Genética a la Enfermedad/epidemiología , Predisposición Genética a la Enfermedad/genética , Genotipo , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/cirugía , Trasplante de Hígado/mortalidad , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Modelos de Riesgos Proporcionales , Factores de Riesgo , Adulto JovenRESUMEN
OBJECTIVE: Acute rejection resulting from alloimmune responses is a major risk factor affecting patient survival following liver transplantation. Since interleukin (IL)-6 can mediate acute rejection, the association between IL-6 gene single nucleotide polymorphisms (SNPs) and incidence of acute rejection in liver transplant recipients was investigated. METHODS: Patients who received liver transplant between January 2005 and December 2010 were typed for IL6-572C/G (rs1800796) polymorphisms using the snapshot technique. Association between genotype and acute rejection was analysed using the SNP Statistics website: http://bioinfo.iconcologia.net/snpstats/start.htm. Allelic and genotypic distributions for rs1800796 were compared among 335 patients with or without acute rejection within the first 6 months following liver transplant. RESULTS: Incidence of acute rejection was 11.94%. A heterozygous CG genotype for IL6-572C/G was associated with a lower acute rejection rate compared with homozygous CC or GG genotypes. CONCLUSION: IL6-572 CG genotype may be related to protection from acute rejection following liver transplant in Han Chinese patients.