MTHFR Gene Polymorphisms and Response to Chemotherapy in Metastatic Colorectal Cancer

Abstract

Ramos-Esquivel and colleagues investigated the association between the first-line fluoropyrimidine-based chemotherapy being administered to patients diagnosed with metastatic colorectal adenocarcinoma and C677T, A1298C single nucleotide polymorphisms (SNPs) of the enzyme methylenetetrahydrofolate reductase (MTHFR). Between January 2019 and November 2020, 68 individuals admitted to San Juan de Dios Hospital in Jose, Costa Rica were subjected to a prospective follow-up. Capecitabine/5-fluorouracil was co-administered with oxaliplatin/irinotecan. Their findings reveal that patients that were homozygotes for the wild-type allele demonstrated a poorer overall response rate as compared to those that possessed one or both MTHFR677T T alleles. MTHFR A1298C genotypes and overall response exhibited no association. Patients with progression-free survival did not contain the MTHFR 677 TT and CT genotypes compared to CC individuals. These conclusions continued to hold post adjustment of confounding factors. A hazard ratio: 1.35; 95% CI, 0.72–2.55; P = 0.34 showed no association between progression-free survival and the MTHFR A1298C SNP. Moreover, no SNP was associated with overall survival. The authors conclude that MTHFR C677T SNP homozygotes and heterozygotes had a better overall response and longer progression-free survival than patients that were homozygous for the wildtype allele. Pharmacogenet Genomics. 2021 Dec 1;31(9):191-199.