C677T and A1298C MTHFR gene polymorphisms and response to fluoropyrimidine-based chemotherapy in Mestizo patients with metastatic colorectal cancer
| Autor: | Ricardo Chinchilla-Monge, Marta Valle, Jad Abbas, Allan Ramos-Esquivel |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Costa Rica
medicine.medical_specialty Genotype Colorectal cancer Single-nucleotide polymorphism Gastroenterology Polymorphism Single Nucleotide Colorectal neoplasms Internal medicine Genetics medicine Humans Genetic Predisposition to Disease General Pharmacology Toxicology and Pharmaceutics Molecular Biology Genetics (clinical) Methylenetetrahydrofolate Reductase (NADPH2) biology Proportional hazards model business.industry Methylenetetrahydrofolate reductase Hazard ratio Odds ratio medicine.disease digestive system diseases Oxaliplatin Irinotecan Case-Control Studies Colonic Neoplasms biology.protein Molecular Medicine Fluorouracil business Colorectal Neoplasms medicine.drug |
| Zdroj: | Pharmacogenetics and Genomics, vol. Publish Ahead of Print, pp. Kérwá Universidad de Costa Rica instacron:UCR |
| ISSN: | 1744-6880 |
| Popis: | Objective: To assess the association between C677T and A1298C methylenetetrahydrofolate reductase (MTHFR) single-nucleotide polymorphisms (SNPs) and response to first-line fluoropyrimidine-based chemotherapy for metastatic colorectal adenocarcinoma. Methods: A total of 68 patients were prospectively followed up in San Juan de Dios Hospital (San José, Costa Rica) from January 2019 to November 2020. Patients received first-line therapy with capecitabine or 5-fluorouracil in combination with oxaliplatin or irinotecan. Germline and somatic DNA was extracted from blood samples and paraffin-embedded tissue, respectively. Overall response rate (partial response + complete response) was assessed according to RECIST 1.1 criteria. Cox regression models were performed to identify the effect of MTHFR C677T and A1298C SNPs on progression-free survival (PFS) and overall survival (OS) (NCT registration number: 03852290). Results: Patients harboring one or both T alleles of the MTHFR C677T SNP had better overall response than homozygous wild-type individuals [odds ratio (OR): 3.21; 95% confidence interval (CI), 1.05–9.81; P = 0.03]. No association was found between the MTHFR A1298C genotypes and overall response (OR: 0.75; 95% CI, 0.26–2.20; P = 0.60). Patients with the MTHFR 677 TT and CT genotypes had longer PFS than CC individuals (hazard ratio: 0.53; 95% CI, 0.28–0.98; P = 0.045), even after adjustment for confounders (hazard ratio: 0.50; 95% CI, 0.25–0.98; P = 0.04). We found no association between the MTHFR A1298C SNP and PFS (hazard ratio: 1.35; 95% CI, 0.72–2.55; P = 0.34). None of the SNPs was associated with OS. Conclusion: Patients carrying at least one mutant allele of the MTHFR C677T SNP had a better overall response and longer PFS than wild-type homozygous patients. UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Centro de Investigación en Hematología y Trastornos Afines (CIHATA) |
| Databáze: | OpenAIRE |
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