[Relationship of methylenetetrahydrofolate reductase C677T polymorphism and chemosensitivity to 5-fluorouracil in gastric carcinoma].
OBJECTIVE
Methylenetrahydrofolate reductase (MTHFR) C677T polymorphism modifies enzyme activity and thus effects the level of 5, 10-methylenetetrahydrofolate (5,10-MTHR), which correlates with the tumor response to 5-fluorouracil (5-FU). This study was to evaluate the effect of MTHFR C677T polymorphism on chemosensitivity and toxicity to 5-FU in patients with gastric carcinoma.


METHODS
A total of 75 patients with histologically confirmed advanced gastric carcinoma were included. All patients received 5-fluoropyrimidine-based chemotherapy. Two milliliters of peripheral blood was extracted from each patient before treatment. PCR-RFLP was used to determine the genotypes of MTHFR, including wild-type homozygotes (C/C), heterozygotes (C/T), and mutant homozygotes (T/T).


RESULTS
C/C genotype presented in 24 patients (24/75, 32.0%), C/T genotype presented in 33 patients (33/75, 44.0%), and T/T genotype presented in 18 patients (18/75, 24.0%). Total response rate of chemotherapy was 29.3%, among which 22 with partial response, 29 with no change, and 24 with progressive disease. Response rate in patients with T/T genotype (20/24, 83.3%) was significantly greater than either that in patients with C/C genotype (2/24, 8.3%) (Chi2=24.01, P< 0.001), or that in patients with C/T genotype (5/33, 15.2%) (Chi2=22.7, P< 0.001). There was no difference of response rate between C/C and C/T genotypes (Chi2=0.6, P=0.439). Multiple variances logistic regression analysis (adjusted for gender, age, chemotherapy regimens, and adjuvant chemotherapy factors) showed that the probability of chemotherapy work on patients with combination of C/C and C/T genotypes was 0.017-fold to that in patients with T/T genotype (95% CI ranging from 0.003 to 0.102, P< 0.001); incidence of treatment-related side effects, vomiting and nausea, was significantly greater in latter patients than in former patients (Chi2=12.264, P=0.002).


CONCLUSIONS
MTHFR C677T polymorphism can predict the effects and toxicity of 5-fluoropyrimidine-based chemotherapy in advanced gastric carcinoma.
Lu
Jian-Wei
JW
Department of Medical Oncology, Jiangsu Province Institute of Cancer Research, Nanjing, Jiangsu 210009, PR China. lujw@medmail.com.cn
Gao
Chang-Ming
CM
Wu
Jian-Zhong
JZ
Sun
Xiao-Feng
XF
Wang
Li
L
Feng
Ji-Feng
JF
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics*
D042965:Methylenetetrahydrofolate Reductase (NADPH2); D005472:Fluorouracil