title: Favorable genetic polymorphisms predictive of clinical outcome of chemoradiotherapy for stage II/III esophageal squamous cell carcinoma in Japanese.
abstract: OBJECTIVE
  This study was performed to find the genetic factors predictive of clinical outcome to a 5-fluorouracil (5-FU)/cisplatin (CDDP)-based chemoradiotherapy (CRT) in Japanese patients with locally advanced esophageal squamous cell carcinoma (ESCC).
  
  
  METHODS
  Thirty-one patients with stage I-IVa ESCC (I/II/III/IVa = 7/7/14/3) were enrolled in this study. One course of treatment consisted of protracted venous infusions (PVIs) of 5-FU (400 mg/m2/24 hours for days 1-5 and 8-12), CDDP (40 mg/m2/3 hours on days 1 and 8) and radiation (2 Gy/d on days 1-5, 8-12, and 15-19), and a 2nd course was successively repeated after a 2-week interval. A total of 8 measurements of the plasma concentration of 5-FU were made using high performance liquid chromatography. Genetic polymorphisms examined herein included those in the genes coding thymidylate synthase (TS), glutathione S-transferase P1 (GSTP1), multidrug resistant transporter MDR1/P-glycoprotein, and intercellular adhesion molecule-1, and in a circadian rhythm-relating gene, CLOCK.
  
  
  RESULTS
  The CR rate depended on stage (P = 0.001), but the analysis was not sufficiently powered to reach a level of statistical significance for the 2-year survival rate (P = 0.061). For stage II/III patients, to have 2 or 3 polymorphisms of 3R/3R of 5'-TSER, a 6 bp of 3'-TSUTR, and GSTP1-Ile105Val resulted in an extensively longer survival (P = 0.020), although no difference was found between 2 groups, with respect to the plasma concentrations of 5-FU and clinicopathologic characteristics.
  
  
  CONCLUSIONS
  The prognostic index may allow predictions of the clinical outcome of a 5-FU/CDDP-based CRT in stage II/III ESCC patients.
authors.affiliation: Division of Diabetes, Digestive and Kidney Diseases, Department of Clinical Molecular Medicine, International Center for Medical Research and Treatment, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Okuno
authors.forename: Takao
authors.initials: T
authors.lastname: Tamura
authors.forename: Motohiro
authors.initials: M
authors.lastname: Yamamori
authors.forename: Naoko
authors.initials: N
authors.lastname: Chayahara
authors.forename: Toshio
authors.initials: T
authors.lastname: Yamada
authors.forename: Ikuya
authors.initials: I
authors.lastname: Miki
authors.forename: Noboru
authors.initials: N
authors.lastname: Okamura
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kadowaki
authors.forename: Daisuke
authors.initials: D
authors.lastname: Shirasaka
authors.forename: Nobuo
authors.initials: N
authors.lastname: Aoyama
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nakamura
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Okumura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Azuma
authors.forename: Masato
authors.initials: M
authors.lastname: Kasuga
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Sakaeda
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D044466:Asian People / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000628:therapy*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000628:therapy*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011379:Prognosis; D011878:Radiotherapy
chemical_list: D002945:Cisplatin; D005472:Fluorouracil