Polymorphism of methylenetetrahydrofolate reductase and sensitivity of stomach cancer to fluoropyrimidine-based chemotherapy.
- Author:
Chang-Ming GAO
1
;
Jian-Wei LU
;
Takezaki TOSHIRO
;
Jian-Zhong WU
;
Hai-Xia CAO
;
Huan-Qiu CHEN
;
Ji-Feng FENG
;
Tajima KAZUO
Author Information
- Publication Type:Journal Article
- MeSH: Adult; Aged; Antimetabolites, Antineoplastic; therapeutic use; Drug Resistance, Neoplasm; genetics; Female; Fluorouracil; therapeutic use; Genotype; Humans; Male; Methylenetetrahydrofolate Reductase (NADPH2); genetics; Middle Aged; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Stomach Neoplasms; drug therapy; enzymology
- From: Chinese Journal of Epidemiology 2004;25(12):1054-1058
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the relationship between polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) C677T or A1298C and the response to fluoropyrimidine (5-FU)-based chemotherapy in advanced stomach cancer (SC).
METHODS75 cases with advanced SC were analyzed. All patients were treated with 5-FU-based chemotherapy and DNA of peripheral blood leukocytes was obtained before therapy. MTHFR genotypes were detected by PCR-RFLP method.
RESULTS(1) Of all the cases, the frequencies of MTHFR C677T C/C, C/T and T/T genotype were 32.0%, 44.0% and 24.0%, while the frequencies of MTHFR A1298C A/A, A/C and C/C genotype were 69.3%, 29.3% and 1.3%, respectively. The overal response rate to 5-FU-based chemotherapy was 29.3%. (2) The response rate to therapy among MTHFR C677T T/T genotype patients (83.3%) was significantly higher than the C677T C/T genotype (15.2%, chi(2) = 22.27, P = 0.000) or the C677T C/C genotype (8.3%, chi(2) = 23.44, P = 0.000). As compared with patients with C677T C allele, patients with C677T T/T genotype had a 7.64-fold sensitivity to 5-FU-based chemotherapy (adjusted for sex, age, prior adjuvant therapy and chemotherapy program, 95% CI: 3.14 - 18.62). The response rate to therapy among patients with MTHFR A1298C A/A genotype (36.5%) was significantly higher than patients with A1298C C allele (13.0%, chi(2) = 4.19, P = 0.041, adjusted OR = 3.75, 95% CI: 0.94 - 14.87). The response rate to therapy among patients with MTHFR C677T T/T and A1298C A/A genotypes (86.7%) was significantly higher than other groups of C677T and A1298C genotypes (15.0%, Fisher exact: P = 0.000, adjusted OR = 6.57, 95% CI: 2.8 - 15.6). (3) The incidence rates of nausea/vomiting in MTHFR C677T T/T, C/T or A1298C A/A genotypes were significantly higher than other genotypes, but the incidence rates of other treatment-related adverse reaction in MTHFR C677T or A1298C genotypes were not significantly different.
CONCLUSIONThese results in the present study suggested that the polymorphisms of MTHFR were associated with clinical response to 5-FU-based chemotherapy, suggesting that MTHFR genotypes could identify advanced SC patients that would be responsive to 5-FU-based chemotherapy.
