The polymorphisms of TS and MTHFR predict survival of gastric cancer patients treated with fluorouracil-based adjuvant chemotherapy in Chinese population.
OBJECTIVE
The aim of this study was to investigate the association of the thymidylate synthase (TS) and methylenetetrahydrofolate reductase (MTHFR) polymorphisms with the clinical outcomes of gastric cancer patients treated with 5-FU-based adjuvant chemotherapy.


METHODS
One-hundred and sixteen patients with gastric cancer were treated with 5-FU-based adjuvant chemotherapy. The TS (a 28-bp tandem repeat polymorphism in the TS enhancer region (TSER) and a 6 bp deletion/insertion polymorphism in the 3'-untranslated region) and MTHFR C677T polymorphisms were determined in blood samples from those patients using PCR and PCR-LDR (ligation detection reaction) method, respectively.


RESULTS
The overall survival (OS) in patients with the TS ins6/ins6 genotype was significantly shorter than those in patients with the del6/del6 (P = 0.017) and ins6/del6 (P = 0.022) genotype. The relapse-free survival (RFS) and OS in patients with the MTHFR C/C genotype were significantly worse than those in patients with the T/T or C/T genotype (P = 0.043 and 0.040, respectively). Cox multivariate analysis also showed that patients with the TS ins6/ins6 genotype have worse OS than patients with the T/T or C/T genotype (HR = 2.437, P = 0.041), and the MTHFR C/C genotype was associated with shorter RFS (HR = 1.723, P = 0.031) and OS (HR = 1.681, P = 0.056). No significant association was found between the TSER polymorphism and the clinical outcomes (P > 0.05).


CONCLUSIONS
The polymorphisms of TS 3'-UTR ins6/del6 and MTHFR C677T appear to be potential prognostic factors in gastric cancer patients treated with 5-FU-based adjuvant chemotherapy, which may allow identification of gastric cancer patients who will benefit from 5-FU chemotherapy.
Huang
Zhao-Hui
ZH
Wuxi Oncology Institute, The Fourth Affiliated Hospital of Suzhou University, 200 Huihe Road, 214062, Wuxi, Jiangsu Province, China. hzhwxsy@yahoo.com.cn
Hua
Dong
D
Li
Li-Hua
LH
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D002681:China / Q000453:epidemiology; D015331:Cohort Studies; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005838:Genotype; D006801:Humans; D007414:Intestinal Neoplasms / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D017384:Sequence Deletion; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics*; D015996:Survival Rate; D020080:Tandem Repeat Sequences; D043823:Taxoids / Q000008:administration & dosage; D013940:Thymidylate Synthase / Q000235:genetics*; D016896:Treatment Outcome
D009944:Organoplatinum Compounds; D043823:Taxoids; D000077150:Oxaliplatin; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013940:Thymidylate Synthase; D005472:Fluorouracil