PMID- 35272420
OWN - NLM
STAT- MEDLINE
DCOM- 20220915
LR  - 20220923
IS  - 2363-8915 (Electronic)
IS  - 2363-8915 (Linking)
VI  - 37
IP  - 3
DP  - 2022 Sep 1
TI  - MTHFR c.665C>T guided fluoropyrimidine therapy in cancer: gender-dependent effect 
      on dose requirements.
PG  - 323-327
LID - 10.1515/dmpt-2021-0219 [doi]
AB  - OBJECTIVES: The fluoropyrimidine derivatives 5-Fluorouracil and Capecitabine are 
      widely used for the treatment of solid tumors. Fluoropyrimidine metabolism 
      involves a cascade of different enzymes, including MTHFR enzyme. MTHFR c.665C>T 
      polymorphism, leading to decreased MTHFR activity, is a potential pharmacogenomic 
      marker for fluoropyrimidine drug response. The aim of the present study was to 
      analyze the association of MTHFR c.665C>T polymorphism with fluoropyrimidine 
      response in terms of therapy induced adverse events (AEs), requirement of dose 
      reduction and delayed drug administration or therapy discontinuation. METHODS: 
      The study group consisted of 313 fluoropyrimidine-treated cancer patients. 
      PCR-RFLP was used to analyze MTHFR c.665C>T polymorphism. RESULTS: In female 
      patients, MTHFR c.665 CT and TT genotypes were associated with dose reduction 
      (p=0.029). In gender stratification, regression analysis adjusted for age of 
      disease onset, body surface area and AE incidence, showed that MTHFR CT and TT 
      genotypes increased both need for fluoropyrimidine dose reduction (OR 5.050, 95% 
      CI 1.346-18.948, p=0.016) and percentage of dose reduction (beta=3.318, 95% C.I. 
      1.056-5.580, p=0.004) in female patients. Such differences were not present in 
      male patients. No other associations were found. CONCLUSIONS: MTHFR c.665C>T 
      polymorphism was associated with fluoropyrimidine dose reduction in female cancer 
      patients. This gender*MTHFR interaction merits further investigation.
CI  - (c) 2022 Charalampia Ioannou et al., published by De Gruyter, Berlin/Boston.
FAU - Ioannou, Charalampia
AU  - Ioannou C
AD  - Laboratory of Pharmacology, Medical School, Democritus University of Thrace, 
      Alexandroupolis, Greece.
AD  - Individualised Medicine & Pharmacological Research Solutions Center (IMPReS), 
      Alexandroupolis, Greece.
FAU - Ragia, Georgia
AU  - Ragia G
AD  - Laboratory of Pharmacology, Medical School, Democritus University of Thrace, 
      Alexandroupolis, Greece.
AD  - Individualised Medicine & Pharmacological Research Solutions Center (IMPReS), 
      Alexandroupolis, Greece.
FAU - Balgkouranidou, Ioanna
AU  - Balgkouranidou I
AD  - Department of Medical Oncology, University General Hospital of Alexandroupolis, 
      Medical School, Democritus University of Thrace, Alexandroupolis, Greece.
FAU - Xenidis, Nikolaos
AU  - Xenidis N
AD  - Department of Medical Oncology, University General Hospital of Alexandroupolis, 
      Medical School, Democritus University of Thrace, Alexandroupolis, Greece.
FAU - Amarantidis, Kyriakos
AU  - Amarantidis K
AD  - Department of Medical Oncology, University General Hospital of Alexandroupolis, 
      Medical School, Democritus University of Thrace, Alexandroupolis, Greece.
FAU - Koukaki, Triantafyllia
AU  - Koukaki T
AD  - Department of Medical Oncology, University General Hospital of Alexandroupolis, 
      Medical School, Democritus University of Thrace, Alexandroupolis, Greece.
FAU - Biziota, Eirini
AU  - Biziota E
AD  - Department of Medical Oncology, University General Hospital of Alexandroupolis, 
      Medical School, Democritus University of Thrace, Alexandroupolis, Greece.
FAU - Kakolyris, Stylianos
AU  - Kakolyris S
AD  - Department of Medical Oncology, University General Hospital of Alexandroupolis, 
      Medical School, Democritus University of Thrace, Alexandroupolis, Greece.
FAU - Manolopoulos, Vangelis G
AU  - Manolopoulos VG
AD  - Laboratory of Pharmacology, Medical School, Democritus University of Thrace, 
      Alexandroupolis, Greece.
AD  - Individualised Medicine & Pharmacological Research Solutions Center (IMPReS), 
      Alexandroupolis, Greece.
AD  - Clinical Pharmacology Unit, Academic General Hospital of Alexandroupolis, 
      Alexandroupolis, Greece.
LA  - eng
PT  - Journal Article
DEP - 20220311
PL  - Germany
TA  - Drug Metab Pers Ther
JT  - Drug metabolism and personalized therapy
JID - 101653409
RN  - 0 (Antimetabolites, Antineoplastic)
RN  - 6804DJ8Z9U (Capecitabine)
RN  - EC 1.5.1.20 (MTHFR protein, human)
RN  - EC 1.5.1.20 (Methylenetetrahydrofolate Reductase (NADPH2))
RN  - U3P01618RT (Fluorouracil)
SB  - IM
MH  - *Antimetabolites, Antineoplastic/therapeutic use
MH  - Capecitabine/therapeutic use
MH  - Female
MH  - Fluorouracil/therapeutic use
MH  - Humans
MH  - Male
MH  - *Methylenetetrahydrofolate Reductase (NADPH2)/genetics
MH  - *Neoplasms/drug therapy/genetics
MH  - Pharmacogenetics
MH  - Polymorphism, Restriction Fragment Length
OTO - NOTNLM
OT  - MTHFR
OT  - TYMS
OT  - chemotherapy response
OT  - fluoropyrimidine
OT  - gender interaction
EDAT- 2022/03/11 06:00
MHDA- 2022/09/16 06:00
CRDT- 2022/03/10 20:18
PHST- 2021/11/19 00:00 [received]
PHST- 2022/02/08 00:00 [accepted]
PHST- 2022/03/11 06:00 [pubmed]
PHST- 2022/09/16 06:00 [medline]
PHST- 2022/03/10 20:18 [entrez]
AID - dmdi-2021-0219 [pii]
AID - 10.1515/dmpt-2021-0219 [doi]
PST - epublish
SO  - Drug Metab Pers Ther. 2022 Mar 11;37(3):323-327. doi: 10.1515/dmpt-2021-0219. 
      eCollection 2022 Sep 1.