Impact of cytokine gene variants on the prediction and prognosis of hepatocellular carcinoma in patients with cirrhosis
| Autor: | Arige Tarhuni, Pierre Nahon, Abdellah Mansouri, Nathalie Charnaux, Pierre Rufat, Erwan Guyot, Nathalie Ganne-Carrié, Michel Beaugrand, Marianne Ziol, Angela Sutton, Richard Moreau, Jean-Claude Trinchet, V. Bourcier, Véronique Grando |
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| Rok vydání: | 2014 |
| Předmět: |
Liver Cirrhosis
Male Oncology medicine.medical_specialty Carcinoma Hepatocellular Cirrhosis Interleukin-1beta Single-nucleotide polymorphism Polymorphism Single Nucleotide Internal medicine Genotype medicine Humans SNP Allele Hepatology Tumor Necrosis Factor-alpha business.industry Genetic heterogeneity Liver Neoplasms Middle Aged Prognosis medicine.disease digestive system diseases Hepatocellular carcinoma Immunology Cytokines Female business Liver cancer |
| Zdroj: | Journal of Hepatology. 61:342-350 |
| ISSN: | 0168-8278 |
| Popis: | Background & Aims Genetic polymorphisms modulate the expression of proinflammatory cytokines. We prospectively assessed the influence of 6 single nucleotide polymorphisms (SNPs) in TNFα , IL6 , and IL1β genes on the risk of hepatocellular carcinoma (HCC) in patients with cirrhosis. Methods TNFα (G-238A, C-863A, G-308A), IL6 (C-174G), and IL1β (C-31T, C-511T) SNPs were assessed in 232 alcoholics and 253 HCV-infected patients with biopsy-proven cirrhosis, prospectively followed-up and screened for HCC. Their influence on HCC development was assessed using the Kaplan-Meier method. Results These variants did not influence the risk of HCC in alcoholic patients. Conversely, two variants influenced the risk of HCC occurrence in patients with HCV-related cirrhosis, namely the TNFα -308 (A) allele (HR=2.4 [1.6–3.7], Log-rank IL1β -31 (T) allele (HR=1.5 [1.1–2.1], Log-rank=0.004). When stratifying HCV-infected patients into four genotypic associations expected to progressively increase TNFα and IL1β production, we observed increasing risk of HCC occurrence (Log-rank TNFα -308 (A) allele was the only genetic trait independently associated with risk of HCC in these patients, along with older age, male gender, BMI, and platelet count. These variables led to construction of a predictive score able to separate patients with HCV-related cirrhosis into three subgroups with progressively increasing 5-year cumulative incidences of 4.7%, 14.1%, and 36.3%, respectively (Log-rank Conclusions Genetic heterogeneity in the TNFα and IL1β gene promoters influences the risk of HCC in patients with HCV-induced cirrhosis. These genetic data, when incorporated into clinical scores, are able to refine selection of risk classes of HCC. |
| Databáze: | OpenAIRE |
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