title: 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.
abstract: BACKGROUND
  Genotypes of tumor necrosis factor alpha (TNF-α) and its surface receptors, TNFRSF1A and TNFRSF1B, have been examined in terms of the progression, metastasis, clinical efficacy, and prognosis of various cancers; however, little is known about their effects on clinical outcome in patients with esophageal squamous cell carcinoma (ESCC). In this study, TNF-α and TNFRSF1A genotypes were retrospectively evaluated in terms of predicting clinical response, long-term survival, and severe acute toxicities in 46 male Japanese ESCC patients treated with definitive 5-fluorouracil (5-FU)/cisplatin (CDDP)-based chemoradiotherapy (CRT).
  
  
  METHODS
  A course consisted of the continuous infusion of 5-FU at 400 mg/m(2)/day for days 1-5 and 8-12, the infusion of CDDP at 40 mg/m(2)/day on days 1 and 8, and radiation at 2 Gy/day on days 1-5, 8-12, and 15-19, with a second course being repeated after a 2-week interval. The TNF-α -1031T>C (rs1799964), -863C>A (rs1800630), -857C>T (rs1799724), -308G>A (rs1800629), -238G>A (rs361525), TNFRSF1A -609G>T (rs4149570), and 36A>G (rs767455) genotypes were evaluated.
  
  
  RESULTS
  The TNF-α -857C>T genotype was found to be predictive of clinical response, i.e., complete response or not (P = 0.010, Fisher's exact test), but had no effect on long-term survival (CC(-857) vs. CT(-857) + TT(-857), P = 0.072, Fisher's exact test, P = 0.070, Log-rank test).
  
  
  CONCLUSIONS
  The TNF-α -857C>T genotype was found to be predictive of clinical response and was more likely to predict long-term survival in Japanese ESCC patients receiving definitive 5-FU/CDDP-based CRT. Further clinical investigations with a larger number of patients or experiments in vitro should be performed to assess the predictive value of this genotype following CRT.
authors.affiliation: 1. Department of Hospital Pharmacy, School of Medicine, Kobe University, Kobe 650-0017, Japan; ; 2. Department of Pharmacotherapy, Programs for Applied Biomedicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8553, Japan;
authors.forename: Hideaki
authors.initials: H
authors.lastname: Omatsu
authors.forename: Akiko
authors.initials: A
authors.lastname: Kuwahara
authors.forename: Motohiro
authors.initials: M
authors.lastname: Yamamori
authors.forename: Megumi
authors.initials: M
authors.lastname: Fujita
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Okuno
authors.forename: Ikuya
authors.initials: I
authors.lastname: Miki
authors.forename: Takao
authors.initials: T
authors.lastname: Tamura
authors.forename: Kohshi
authors.initials: K
authors.lastname: Nishiguchi
authors.forename: Noboru
authors.initials: N
authors.lastname: Okamura
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nakamura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Azuma
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hirano
authors.forename: Koichiro
authors.initials: K
authors.lastname: Ozawa
authors.forename: Midori
authors.initials: M
authors.lastname: Hirai
mesh_terms: D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003131:Combined Modality Therapy; D064420:Drug-Related Side Effects and Adverse Reactions / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D002945:Cisplatin; D005472:Fluorouracil
keywords: chemoradiotherapy; clinical response; esophageal squamous cell carcinoma; prognosis; tumor necrosis factor.