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TNF-α gene promoter polymorphisms and risk of venous thromboembolism in gastrointestinal cancer patients undergoing chemotherapy.
Roselli, M; Ferroni, P; Rolfo, C; Peeters, M; Palmirotta, R; Formica, V; Ludovici, G; Laudisi, A; De Marchis, M L; La Farina, F; Russo, A; Guadagni, F.
Afiliação
  • Roselli M; Medical Oncology, Department of System Medicine, Tor Vergata Clinical Center, University of Rome 'Tor Vergata', Rome.
  • Ferroni P; Department of Advanced Biotechnologies and Bioimaging, IRCCS San Raffaele Pisana, Rome, Italy.
  • Rolfo C; Phase I - Early Clinical Trials Unit, Department of Oncology, Antwerp University Hospital (UZA); MOCA (Multidisciplinary Oncology Center Antwerp), Antwerp University Hospital, Edegem, Belgium. Electronic address: christian.rolfo@uza.be.
  • Peeters M; MOCA (Multidisciplinary Oncology Center Antwerp), Antwerp University Hospital, Edegem, Belgium.
  • Palmirotta R; Department of Advanced Biotechnologies and Bioimaging, IRCCS San Raffaele Pisana, Rome, Italy.
  • Formica V; Medical Oncology, Department of System Medicine, Tor Vergata Clinical Center, University of Rome 'Tor Vergata', Rome.
  • Ludovici G; Department of Advanced Biotechnologies and Bioimaging, IRCCS San Raffaele Pisana, Rome, Italy.
  • Laudisi A; Medical Oncology, Department of System Medicine, Tor Vergata Clinical Center, University of Rome 'Tor Vergata', Rome.
  • De Marchis ML; Department of Advanced Biotechnologies and Bioimaging, IRCCS San Raffaele Pisana, Rome, Italy.
  • La Farina F; Department of Advanced Biotechnologies and Bioimaging, IRCCS San Raffaele Pisana, Rome, Italy.
  • Russo A; Section of Medical Oncology, Department of Surgical and Oncology Sciences, University of Palermo, Palermo, Italy.
  • Guadagni F; Department of Advanced Biotechnologies and Bioimaging, IRCCS San Raffaele Pisana, Rome, Italy.
Ann Oncol ; 24(10): 2571-2575, 2013 Oct.
Article em En | MEDLINE | ID: mdl-23852308
BACKGROUND: TNF-α has been proposed as a predictive factor for venous thromboembolism (VTE). Genetic polymorphisms could regulate TNF-α production. However, the relationship between TNFA gene variants and VTE is not clarified. This study aims to investigate the predictive role of five different TNFA gene promoter SNPs, or their haplotype combination(s), for a first VTE episode in gastrointestinal cancer out-patients treated with chemotherapy. PATIENTS AND METHODS: Serum TNF-α levels and TNFA -863C/A, -857C/T, -376G/A, -308G/A and -238G/A gene promoter polymorphisms were retrospectively evaluated in 314 subjects, including 157 controls and 157 Caucasian patients with histologically diagnosed GI cancers beginning chemotherapy delivery (5-fluorouracil either as monotherapy or in combination with platinum compounds or irinotecan). RESULTS: Haplotype analysis showed that a five-loci haplotype (CTGGG haplotype) has higher frequency in GI cancer patients who developed VTE (n = 15) during chemotherapy [odds ratio = 2.7, 95% confidence interval (CI) 1.04-7.11, P = 0.04]. GI patients who remained VTE-free did not differ in CTGGG haplotype frequency from controls. No association was observed between serum TNF-α levels and TNFA haplotype, but both were independent predictors of VTE. Approximately 20% of GI cancer patients carrying the CTGGG haplotype developed VTE compared with 4% of the remaining 101 patients (hazard ratio = 5.6, 95% CI 1.8-17.6, P = 0.003). CONCLUSION: These results suggest that TNFA might represent a candidate gene contributing to VTE pathogenesis in GI cancer patients and suggest that VTE risk during chemotherapy might be genetically identified. Validation studies are needed for translation into clinical practice.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fator de Necrose Tumoral alfa / Tromboembolia Venosa / Neoplasias Gastrointestinais Tipo de estudo: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2013 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fator de Necrose Tumoral alfa / Tromboembolia Venosa / Neoplasias Gastrointestinais Tipo de estudo: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2013 Tipo de documento: Article