Favorable genetic polymorphisms predictive of clinical outcome of chemoradiotherapy for stage II/III esophageal squamous cell carcinoma in Japanese.
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.
Okuno
Tatsuya
T
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.
Tamura
Takao
T
Yamamori
Motohiro
M
Chayahara
Naoko
N
Yamada
Toshio
T
Miki
Ikuya
I
Okamura
Noboru
N
Kadowaki
Yuko
Y
Shirasaka
Daisuke
D
Aoyama
Nobuo
N
Nakamura
Tsutomu
T
Okumura
Katsuhiko
K
Azuma
Takeshi
T
Kasuga
Masato
M
Sakaeda
Toshiyuki
T
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
D002945:Cisplatin; D005472:Fluorouracil