Association of C677T and A1298C MTHFR Polymorphisms and Fluoropyrimidine-induced Toxicity in Mestizo Patients With Metastatic Colorectal Cancer.
Anticancer Res
; 40(8): 4263-4270, 2020 Aug.
Article
de En
| MEDLINE
| ID: mdl-32727753
ABSTRACT
BACKGROUND/AIM:
Enzymatic variants involved in fluoropyrimidine metabolism have been associated with adverse events (AEs). We assessed the association between C677T (rs1801133) and A1298 (rs1801131) methylenetetrahydrofolate reductase (MTHFR) polymorphisms and AEs in patients with first-line fluoropyrimidine-based chemotherapy. PATIENTS ANDMETHODS:
Fifty patients with metastatic colorectal cancer were prospectively followed-up during the first 4 cycles of fluoropyrimidine-based treatment to assess AEs. Germline DNA was analyzed to determine the C677T and A1298C MTHFR polymorphisms. The associations between MTHFR polymorphisms and toxicity were examined.RESULTS:
Individuals carrying at least one mutant allele of the MTHFR C677T polymorphism had increased risk to experience anemia (OR=1.69, 95% CI=1.13-2.53, p=0.005), neutropenia (OR=2.27, 95% CI=1.47-3.42, p<0.001) thrombocytopenia (OR=1.91, 95% CI=1.30-2.70, p<0.001), neuropathy (OR=1.77, 95% CI=1.16-2.70, p=0.02), diarrhea (OR=1.69, 95% CI=1.13-2.53, p=0.005), and hand-foot syndrome (OR=1.56, 95% CI=1.08-2.27, p=0.013), compared to patients carrying the wild type alleles. The presence of the mutant allele C of the MTHFR A1298C polymorphism was associated with increased risk of anemia (OR=2.75, 95% CI=1.01-7.48, p=0.02) and thrombocytopenia (OR=3.14, 95% CI=1.01-9.78, p=0.03); however, the prevalence of this allele in the sample was quite low (20%).CONCLUSION:
MTHFR C677T and A1298C polymorphisms predicted toxicity in a subset of Mestizo patients with colorectal adenocarcinoma.Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Tumeurs colorectales
/
Ethnies
/
Protocoles de polychimiothérapie antinéoplasique
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Polymorphisme de nucléotide simple
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Methylenetetrahydrofolate reductase (NADPH2)
/
Antimétabolites antinéoplasiques
Type d'étude:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limites:
Aged
/
Female
/
Humans
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Male
/
Middle aged
Pays/Région comme sujet:
America central
/
Costa rica
Langue:
En
Journal:
Anticancer Res
Année:
2020
Type de document:
Article
Pays d'affiliation:
Espagne