[Relationship of methylenetetrahydrofolate reductase C677T polymorphism and chemosensitivity to 5-fluorouracil in gastric carcinoma].

Abstract

BACKGROUND & 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.

• Authors: Jian-Wei Lu, Chang-Ming Gao, Jian-Zhong Wu, Xiao-Feng Sun, Li Wang, Ji-Feng Feng
• Journal: Ai zheng = Aizheng = Chinese journal of cancer (Ai Zheng) Vol. 23 Issue 8 Pg. 958-62 (Aug 2004) China
• PMID: 15301724 (Publication Type: English Abstract, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Methylenetetrahydrofolate Reductase (NADPH2)
• Fluorouracil

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Female
• Fluorouracil (administration & dosage, adverse effects)
• Humans
• Male
• Methylenetetrahydrofolate Reductase (NADPH2) (genetics)
• Middle Aged
• Nausea (chemically induced)
• Neoplasm Staging
• Neutropenia (chemically induced)
• Polymerase Chain Reaction
• Polymorphism, Restriction Fragment Length
• Stomach Neoplasms (drug therapy, genetics)