TNFRSF1B A1466G genotype is predictive of clinical efficacy after treatment with a definitive 5-fluorouracil/cisplatin-based chemoradiotherapy in Japanese patients with esophageal squamous cell carcinoma

Abstract

BackgroundCurrently definitive 5-fluorouracil (5-FU)/cisplatin (CDDP) -based chemotherapy is recognized as one of the most promising treatments for esophageal cancer. A series of studies performed found genetic polymorphisms and the plasma concentration of 5-FU to be predictive of acute severe toxicities and clinical response. Genetic polymorphisms of tumor necrosis factor (TNF) -α and its surface receptors, TNFRSF1A and TNFRSF1B have been examined in terms of susceptibility to various cancers. In this study, genetic polymorphisms of TNFRSF1B gene were evaluated Japanese esophageal squamous cell carcinoma (ESCC) patients treated with the definitive 5-FU/CDDP-based chemoradiotherapy and their predictive values of prognosis or severe acute toxicities were assessed.MethodsForty-six patients with ESCC were treated with the definitive 5-FU/CDDP-based chemoradiotherapy, one course of which consisted of the continuous infusion of 5-FU for days 1-5 and 8-12, the infusion of CDDP on days 1 and 8, and the radiation at 2 Gy/day on days 1-5, 8-12, and 15-19, with a second course repeated after 2-week interval. Genetic polymorphisms of a TNF-α receptor TNFRSF1B gene were determined by a TaqMan® MGB probe-based polymerase chain reaction.ResultsThe genotype of TNFSR1B A1466G, but not M196R/T587G or C1493T, was found to be predictive of clinical response, i.e., a complete response or not (p = 0.040). Clinical response was predicted by tumor size (p = 0,002), lymph node metastasis (p = 0.007), distant metastasis (p = 0.001) and disease stage (p < 0.001), but TNFRSF1B A1466G genotype was independent of these factors.ConclusionsGenetic polymorphism of TNFRSF1B A1466G was found to be predictive response in Japanese ESCC patients with a definitive 5-FU/CDDP-based chemoradiotherapy. Further clinical investigation with a large number of patients or experiments in vitro should be performed to assess the predictive value of TNFRSF1B A1466G genotype after chemoradiotherapy.

Tumor necrosis factor receptor-II nt587 polymorphism in Chinese Han patients with ankylosing spondylitis

“…Previous studies have shown that an amino acid substitution (methionine to arginine) is caused by the T to G SNP at TNFRII nt587, and that the amino acid substitution is responsible for its proteolytic cleavage, which produces the soluble form of TNFRII (sTNFR) (Beltinger et al, 1996;Oregon-Romero et al, 2006;Kuwahara et al, 2010). STNFR and mTNFR can compete to combine with TNF, which might affect the biological functions of TNF.…”

Résultats à long terme de la chimioradiothérapie néoadjuvante des cancers de l’œsophage : étude rétrospective monocentrique sur 102 patients

“…Des polymorphismes génétiques sont en cours d'identification comme le TNFRSF1B et seraient corrélés avec une meilleure réponse in vitro aux protocoles de chimiothérapie associant de la 5-fluoro-uracile et du cisplatine, ce qui nécessite encore la preuve d'un impact clinique [54].…”

TNF-α -857C>T Genotype is Predictive of Clinical Response after Treatment with Definitive 5-Fluorouracil/cisplatin-based Chemoradiotherapy in Japanese Patients with Esophageal Squamous Cell Carcinoma

“…Studies have been performed to evaluate the effects of genetic polymorphisms on clinical response, survival or severe acute toxicities during treatment with definitive 5-FU/CDDP-based CRT in Japanese patients with ESCC 23-27. They were conducted with the authorization of the Institutional Review Board (IRB) and followed the Medical Research Council guidelines of Kobe University.…”

“…Predicting therapeutic responses is important in definitive CRT prior to the initiation of treatment; we previously reported a significant correlation between clinical response and survival, and showed that the TNFRSF1B 1466A/G (rs1061624) genotype could predict clinical response with definitive 5-FU/cisplatin (CDDP)-based CRT in 46 male Japanese patients with ESCC 23. Although these findings suggest that TNF-α and its receptors may play a critical role in clinical response and survival, to the best of our knowledge, no published study has investigated associations between the polymorphisms of TNF-α and TNFRSF1A genes and the prediction of clinical outcome in ESCC patients treated with definitive CRT.…”