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.
BACKGROUND
Currently 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) -alpha 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.


METHODS
Forty-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-alpha receptor TNFRSF1B gene were determined by a TaqMan(R) MGB probe-based polymerase chain reaction.


RESULTS
The 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.


CONCLUSIONS
Genetic 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.
Kuwahara
Akiko
A
School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya 663-8179, Japan.
Yamamori
Motohiro
M
Fujita
Megumi
M
Okuno
Tatsuya
T
Tamura
Takao
T
Kadoyama
Kaori
K
Okamura
Noboru
N
Nakamura
Tsutomu
T
Sakaeda
Toshiyuki
T
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D005472:Fluorouracil / Q000008:administration & dosage; D005838:Genotype; D006801:Humans; D007564:Japan; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D011879:Radiotherapy Dosage; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics*; D015996:Survival Rate; D016896:Treatment Outcome
D047889:Receptors, Tumor Necrosis Factor, Type II; C415902:TNFRSF1B protein, human; D002945:Cisplatin; D005472:Fluorouracil