PMID- 32727753
OWN - NLM
STAT- MEDLINE
DCOM- 20200821
LR  - 20211204
IS  - 1791-7530 (Electronic)
IS  - 0250-7005 (Linking)
VI  - 40
IP  - 8
DP  - 2020 Aug
TI  - Association of C677T and A1298C MTHFR Polymorphisms and Fluoropyrimidine-induced 
      Toxicity in Mestizo Patients With Metastatic Colorectal Cancer.
PG  - 4263-4270
LID - 10.21873/anticanres.14428 [doi]
AB  - 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 AND METHODS: 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.
CI  - Copyright(c) 2020, International Institute of Anticancer Research (Dr. George J. 
      Delinasios), All rights reserved.
FAU - Ramos-Esquivel, Allan
AU  - Ramos-Esquivel A
AD  - Department of Pharmacology, Therapeutics, and Toxicology, Autonomous University 
      of Barcelona, Barcelona, Spain allan.ramos@ucr.ac.cr.
AD  - Research Center in Hematology and Related Disorders CIHATA, University of Costa 
      Rica, San Jose, Costa Rica.
FAU - Chinchilla, Ricardo
AU  - Chinchilla R
AD  - Research Center in Hematology and Related Disorders CIHATA, University of Costa 
      Rica, San Jose, Costa Rica.
FAU - Valle, Marta
AU  - Valle M
AD  - Department of Pharmacology, Therapeutics, and Toxicology, Autonomous University 
      of Barcelona, Barcelona, Spain.
LA  - eng
PT  - Journal Article
PL  - Greece
TA  - Anticancer Res
JT  - Anticancer research
JID - 8102988
RN  - 0 (Antimetabolites, Antineoplastic)
RN  - 0 (Organoplatinum Compounds)
RN  - EC 1.5.1.20 (MTHFR protein, human)
RN  - EC 1.5.1.20 (Methylenetetrahydrofolate Reductase (NADPH2))
RN  - Q573I9DVLP (Leucovorin)
RN  - U3P01618RT (Fluorouracil)
RN  - Folfox protocol
SB  - IM
MH  - Aged
MH  - Antimetabolites, Antineoplastic/*therapeutic use/*toxicity
MH  - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage
MH  - Colorectal Neoplasms/*drug therapy/pathology
MH  - Costa Rica
MH  - Ethnicity/*genetics
MH  - Female
MH  - Fluorouracil/administration & dosage
MH  - Humans
MH  - Leucovorin/administration & dosage
MH  - Male
MH  - Methylenetetrahydrofolate Reductase (NADPH2)/*genetics
MH  - Middle Aged
MH  - Neoplasm Metastasis
MH  - Organoplatinum Compounds/administration & dosage
MH  - *Polymorphism, Single Nucleotide
MH  - Prospective Studies
OTO - NOTNLM
OT  - Mestizo population
OT  - Metastatic colorectal cancer
OT  - SNPs
OT  - fluoropyrimidine-based chemotherapy
OT  - methylenetetrahydrofolate reductase
OT  - side effects
EDAT- 2020/07/31 06:00
MHDA- 2020/08/22 06:00
CRDT- 2020/07/31 06:00
PHST- 2020/05/15 00:00 [received]
PHST- 2020/06/07 00:00 [revised]
PHST- 2020/06/24 00:00 [accepted]
PHST- 2020/07/31 06:00 [entrez]
PHST- 2020/07/31 06:00 [pubmed]
PHST- 2020/08/22 06:00 [medline]
AID - 40/8/4263 [pii]
AID - 10.21873/anticanres.14428 [doi]
PST - ppublish
SO  - Anticancer Res. 2020 Aug;40(8):4263-4270. doi: 10.21873/anticanres.14428.