Relationship of polymorphism of the tandem repeat sequence in the thymidylate synthase gene and the survival of stage III colorectal cancer patients receiving adjuvant 5-flurouracil-based chemotherapy.
BACKGROUND
The aim of this study was to determine whether the different polymorphisms in the thymidylate synthase (TS) gene, novel G>C single nucleotide polymorphism (SNP) and variable number of tandem repeat (VNTR), may be related with disease-free survival (DFS) in patients with stage III colorectal cancer receiving adjuvant chemotherapy.


METHODS
The study included 201 patients with pathologic TNM stage III colon cancer who received adjuvant 5-fluorouracil (5-FU)-based chemotherapy after surgery. DNA was extracted from fresh tumor tissue and sequenced. Patients with TS genotypes of 2R3G, 3C3G, or 3G3G were assigned to a high expression group, and those with 2R2R, 2R3C, or 3C3C, to a low expression group.


RESULTS
Frequencies of the TS tandem repeat polymorphisms among the tumor genotypes were 6.0% in 2R2R, 25.4% in 2R3R, and 68.7% in 3R3R. The low expression group included 52 patients (25.9%), and the high expression group included 149 patients (74.1%). Groups classified according to possession of VNTR, SNP, and low- or high-expression genotypes did not differ significantly in DFS. In multivariate analysis, only tumor stage showed significant prognostic value (hazard ratio (HR) 2.05, 95% CI = 1.24-3.37, P = 0.005).


CONCLUSIONS
TS polymorphisms do not predict clinical outcome of colorectal cancer patients treated with adjuvant 5-FU-based chemotherapy.
Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul 135-710, Korea.
Chi-Min
CM
Park
Woo Yong
WY
Lee
Ho-Kyung
HK
Chun
Yong Beom
YB
Cho
Hae Ran
HR
Yun
Jin Seok
JS
Heo
Seong Hyeon
SH
Yun
Hee Cheol
HC
Kim
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D013940:Thymidylate Synthase / Q000235:genetics*
D013940:Thymidylate Synthase; D005472:Fluorouracil