Polymorphism at the 3'-UTR of the thymidylate synthase gene: a potential predictor for outcomes in Caucasian patients with esophageal adenocarcinoma treated with preoperative chemoradiation.
OBJECTIVE
To test the hypothesis that TS3'UTR polymorphisms predict outcomes in 146 Caucasian patients with esophageal adenocarcinoma treated with preoperative 5-fluorouracil-based chemoradiation.


METHODS
DNA was extracted from hematoxylin-and-eosin stained histologic slides of normal esophageal or gastric mucosa sections from paraffin blocks of esophagectomy specimens. Genotypes of the TS3'UTR polymorphism were determined by polymerase chain reaction for a 6-bp insertion. The genotype groups (0bp/0bp, 6bp/0bp, and 6bp/6bp) were compared for clinical features and overall survival, recurrence-free-survival, locoregional control (LRC), and distant metastasis control. Multivariable Cox regression analyses were performed to find independent predictors for the stated outcomes.


RESULTS
There was a trend of association between 6bp/6bp genotype and a decreased risk of local regional recurrence (hazards ratio = 0.211, 95% confidence interval = 0.041-1.095, p = 0.06) compared with other genotypes. There was a trend that patients with 6bp/6bp genotype had a higher 3-year probability of LRC compared with patients with the other two genotypes combined (p = 0.07); however, the difference was not statistically significant.


CONCLUSIONS
The null hypotheses were not rejected in this study, probably owing to small sample size or the single gene examined. Prospective studies with adequate statistical power analyzing a family of genes involved in the 5-fluorouracil metabolism are needed to assess genetic determinants of treatment-related outcomes in esophageal adenocarcinoma.
Liao
Zhongxing
Z
Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. zliao@mdanderson.org
Liu
Hongji
H
Swisher
Stephen G
SG
Wang
Luo
L
Wu
Tsung-Teh
TT
Correa
Arlene M
AM
Roth
Jack A
JA
Cox
James D
JD
Komaki
Ritsuko
R
Ajani
Jaffer A
JA
Wei
Qingyi
Q
D020413:3' Untranslated Regions / Q000235:genetics*; D000230:Adenocarcinoma / Q000201:enzymology* / Q000208:ethnology / Q000401:mortality; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D003131:Combined Modality Therapy; D004938:Esophageal Neoplasms / Q000201:enzymology* / Q000208:ethnology / Q000401:mortality; D016629:Esophagectomy; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012044:Regression Analysis; D016019:Survival Analysis; D013940:Thymidylate Synthase / Q000235:genetics*; D044465:White People
D020413:3' Untranslated Regions; D000964:Antimetabolites, Antineoplastic; D013940:Thymidylate Synthase; D005472:Fluorouracil