TNF-alpha has been proposed as a predictive factor for venous thromboembolism (VTE). Genetic polymorphisms could regulate TNF-alpha 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.Serum TNF-alpha 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).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-alpha 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).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.

TNF-α gene promoter polymorphisms and risk of venous thromboembolism in gastrointestinal cancer patients undergoing chemotherapy

Ferroni, P;Guadagni, F
2013-01-01

Abstract

TNF-alpha has been proposed as a predictive factor for venous thromboembolism (VTE). Genetic polymorphisms could regulate TNF-alpha 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.Serum TNF-alpha 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).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-alpha 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).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.
2013
chemotherapy
gastrointestinal cancer
single nucleotide polymorphisms
tumour necrosis factor-α
venous thromboembolism
Adult
Aged
Aged, 80 and over
Antimetabolites, Antineoplastic
Antineoplastic Agents, Phytogenic
Camptothecin
Case-Control Studies
Female
Fluorouracil
Gastrointestinal Neoplasms
Genetic Predisposition to Disease
Haplotypes
Humans
Irinotecan
Male
Middle Aged
Polymorphism, Single Nucleotide
Promoter Regions, Genetic
Retrospective Studies
Risk
Tumor Necrosis Factor-alpha
Venous Thromboembolism
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.12078/11486
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