Impact of genetic variants of RFC1, DHFR and MTHFR in osteosarcoma patients treated with high-dose methotrexate

The Pharmacogenomics Journal
S JabeenV N Kristensen

Abstract

Osteosarcoma patients are commonly treated with high doses of methotrexate (MTX). MTX is an analog of folate, which is essential for DNA synthesis. Genetic polymorphism at single nucleotide can be indicative to the prognostic outcome in patients. Germ-line variants in candidate genes, coding for enzymes active in the metabolism of MTX, were studied in 62 osteosarcoma patients. Patients harboring the GG genotype in reduced folate carrier 1 (RFC1) rs1051266 had significantly better survival in comparison with patients having the AA genotype (P=0.046). These patients also had a lower frequency of metastasis (15%, P=0.029). Also patients homozygous for the G allele of rs1053129 in the dihydrofolate reductase (DHFR) gene were more likely to have a metastasis (45%, P= 0.005), and the methylenetetetrahydrofolate reductase (MTHFR) 677C allele was associated with higher degree of liver toxicity (88%, P=0.007). The study suggests that germ-line variants in the MTX metabolic pathway are associated with survival and side effects in patients treated with MTX.

References

Jan 1, 1985·Pharmacology & Therapeutics·I D Goldman, L H Matherly
Oct 1, 1994·Arthritis and Rheumatism·M E WeinblattE Gall
Jan 1, 1996·Stem Cells·J R BertinoD Banerjee
Nov 1, 2001·The Journal of Molecular Diagnostics : JMD·J D McNairnA E Shrimpton
Feb 1, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Sally S IngramHarvey J Cohen
Feb 1, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Stefan S BielackKurt Winkler
May 25, 2002·Science·Stacey B GabrielDavid Altshuler
Jun 27, 2002·American Journal of Pharmacogenomics : Genomics-related Research in Drug Development and Clinical Practice·B Schwahn, R Rozen
Dec 18, 2003·Annals of Oncology : Official Journal of the European Society for Medical Oncology·M SerraP Picci
Aug 7, 2004·Bioinformatics·J C BarrettM J Daly
May 5, 2006·The Proceedings of the Nutrition Society·Ivon J M van der LindenHenk J Blom
Jun 1, 2006·Expert Review of Neurotherapeutics·Myke R GreenMarc Chamberlain
Sep 12, 2006·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Lina WangHongbing Shen
Jan 5, 2007·Nature Clinical Practice. Rheumatology·Joost W van der HeijdenGerrit Jansen
May 24, 2008·International Journal of Cancer. Journal International Du Cancer·Silje H NordgardVessela N Kristensen
Mar 12, 2009·Biology of the Cell·Sangeeta Chatterjee, Jayanta K Pal
Mar 10, 2010·Cancer Treatment and Research·Giulia Ottaviani, Norman Jaffe
Jun 29, 2011·British Journal of Clinical Pharmacology·Laila HolmboeKirsten Sundby Hall
Apr 25, 2012·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Lin YangLuhang Xu
Aug 24, 2012·Journal of Investigative Medicine : the Official Publication of the American Federation for Clinical Research·Marco Antonio Leyva-VázquezBerenice Illades-Aguiar

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Citations

Sep 30, 2015·Journal of the American Academy of Dermatology·Zhifang ZhaiZhu Shen
May 5, 2016·Cancer Chemotherapy and Pharmacology·Jared M CampbellMicah D J Peters
Jun 1, 2016·The Pharmacogenomics Journal·M Serra, C M Hattinger
Jun 30, 2016·Drug Discovery Today·Hanneke I VosDunja Maroeska W M Te Loo
Sep 14, 2016·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Ruud H WijdevenJacques Neefjes
Sep 13, 2016·International Journal of Molecular Sciences·Vid MlakarMarc Ansari
Oct 21, 2016·Expert Opinion on Drug Metabolism & Toxicology·Claudia Maria HattingerMassimo Serra
Dec 30, 2017·Molecular and Clinical Oncology·Tomoko KurimotoToshiaki Shimizu
Mar 25, 2020·Human Genetics·Qingyang XiaoVolker M Lauschke
Jul 8, 2020·International Journal of Molecular Sciences·Claudia Maria HattingerMassimo Serra
Feb 7, 2021·BMC Musculoskeletal Disorders·Wei LiuGuangrong Ji
Apr 2, 2021·Critical Reviews in Oncology/hematology·Hedy MaagdenbergBruce C Carleton

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