Methylenetetrahydrofolate reductase polymorphism (677 C>T) predicts long time to progression in metastatic colon cancer treated with 5-fluorouracil and folinic acid.
OBJECTIVE
Fluoropyrimidine-based chemotherapy is the most common treatment for unresectable metastatic colorectal cancer (m-CRC). Therapy with 5-FU/folinic acid (FA) continues to be a standard treatment in developing countries. Pharmacogenomics allows the tailoring of cancer therapy to the patient. The polymorphism 677C>T of the methylenetetrahydrofolate reductase (MTHFR) gene seems to influence the effectiveness of treatment with 5-FU. We undertook this study to evaluate the frequency of MTHFR 677C>T polymorphism and its relationship to the time to progression (TTP) and overall survival (OS) in m-CRC treated with 5-FU/FA.


METHODS
The MTHFR 677C>T polymorphism was determined using PCR and allele-specific digestion. The clinical variables, TTP and OS, were analyzed in each case and compared between wild-type and variant polymorphic groups.


RESULTS
Among 34 patients (12 males and 22 females), we detected eight wild-type homozygous patients (CC; 24%), nine variant homozygous (TT; 26%), and 17 heterozygous (CT; 50%) individuals. The median TTP in patients with the MTHFR 677 CC, CT, and TT genotypes was 3.43, 4.77, and 4.80 months, respectively (p = 0.047, log rank). A longer TTP was observed in patients with polymorphic variant (CT and TT) compared with the wild-type homozygous patients (4.80 vs. 3.43 months; p = 0.031, log rank).


CONCLUSIONS
In this study, the frequency of the MTHFR 677C>T polymorphism is 50% among m-CRC Mexican patients. The results of this study appear to show that the presence of the MTHFR 677C>T polymorphism is associated with longer TTP and OS in m-CRC treated with 5-FU/FA.
Departamento de Oncología Médica, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico.
Omar
O
Castillo-Fernández
Miguel
M
Santibáñez
Aldo
A
Bauza
Germán
G
Calderillo
Clementina
C
Castro
Roberto
R
Herrera
Alberto
A
Serrano
Oscar
O
Arrieta
Luis A
LA
Herrera
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics* / Q000556:secondary; D018450:Disease Progression; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D013997:Time Factors
D000964:Antimetabolites, Antineoplastic; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D002955:Leucovorin; D005472:Fluorouracil