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Polymorphism in the Thymidylate Synthase Promoter Enhancer Region Is Not an Efficacious Marker for Tumor Sensitivity to 5-Fluorouracil-based Oral Adjuvant Chemotherapy in Colorectal Cancer
Ist Teil von
Clinical cancer research, 2003-09, Vol.9 (10), p.3700-3704
Ort / Verlag
Philadelphia, PA: American Association for Cancer Research
Erscheinungsjahr
2003
Quelle
MEDLINE
Beschreibungen/Notizen
Thymidylate synthase (TS) is the target enzyme of 5-fluoropyrimidines. The TS gene promoter enhancer region (TSER) possesses tandem, repeated, regulatory sequences that are polymorphic in humans. This polymorphism has been reported to influence
TS expression in vitro and in vivo . In this study, we assessed whether or not the TSER genotype is an efficacious marker for tumor sensitivity to 5-fluorouracil (5-FU)-based oral adjuvant chemotherapy for colorectal
cancer. One hundred and thirty-five Japanese patients who received curative resection and 5-FU-based oral adjuvant chemotherapy
were studied. TSER genotypes of the tumors were analyzed by PCR. The numbers of repeated sequences of representative bands were determined by
direct sequence. The genotypes of two-/two-repeats ( TSER 2/2), two-/three-repeats ( TSER 2/3), three-/three-repeats ( TSER 3/3), and three-/five-repeats ( TSER 3/5) were found in 11 (8.1%), 32 (23.7%), 85 (63.0%), and 7 (5.2%) tumors, respectively. Patients were classified into two
groups: TSER 2/2 or 2/3 group; and the TSER 3/3 group. The relationship between the TSER genotype group and disease-free intervals was analyzed by univariate and multivariate analyses. Five-year disease-free survivals
of the TSER 2/2 or 2/3 group and the TSER 3/3 group were 77% and 75%, respectively ( P = 0.89). Multivariate analysis revealed that stage was the only independent prognostic factor and that the TSER genotype did not have a prognostic significance (hazard ratio for TSER 3/3, 0.91; P = 0.84). In conclusion, TSER genotype is not an efficacious marker for tumor sensitivity to 5-FU-based oral adjuvant chemotherapy for Japanese colorectal
cancer patients after curative resection.