667C>T and 1298A>C polymorphisms of MTHFR do not predict response to methotrexate in patients with gestational trophoblastic neoplasia.

Approximately one third of patients treated with methotrexate for gestational trophoblastic neoplasia (GTN) following a molar pregnancy are reported to develop resistance to methotrexate and need to change to different chemotherapeutic agents. Previous studies, in other clinical settings, have suggested that polymorphisms in key folate metabolising enzymes such as 5,10-methylenetetrahydrofolate reductase (MTHFR) influence both toxicity and efficacy of methotrexate. Our objective was to investigate the impact of two common functional MTHFR polymorphisms, 677C>T and 1298A>C, on the efficacy of methotrexate in women treated for GTN following a molar pregnancy.
DNA from 121 women treated with methotrexate for GTN was genotyped for the 677C>T and 1298A>C polymorphisms using TaqMan SNP Genotyping Assays. In 64 cases these polymorphisms were also genotyped in the antecedent molar pregnancy, using DNA extracted from archival blocks of tissue. Response to methotrexate was evaluated with reference to serial human chorionic gonadotrophin (hCG) levels in patient serum.
No significant association was found between the genotype of the patient, or presence of the variant allele, and clinical response to methotrexate therapy for either the 677C>T or the 1298A>C SNP. No significant association was found between the genotypes of the molar tissue and response to methotrexate. In molar tissue there was a significant reduction in the expected number with the 677TT genotype suggesting the 677C>T SNP may identify a subgroup of molar pregnancies less likely to progress to GTN.
Neither the genotype for the 677C>T SNP or the 1298A>C SNP in MTHFR predict the therapeutic outcomes of women treated with single agent methotrexate for GTN.
AuthorsLidia Lasecka, Peter H Dixon, Mariam Molokhia, Nima Sharma, Annabel Schleh, Chiuhui Mary Wang, Jennifer H Steel, Michael J Seckl, Philip M Savage, Rosemary A Fisher
JournalGynecologic oncology (Gynecol Oncol) Vol. 123 Issue 3 Pg. 605-9 (Dec 2011) ISSN: 1095-6859 [Electronic] United States
PMID21920590 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2011 Elsevier Inc. All rights reserved.
Chemical References
  • Antimetabolites, Antineoplastic
  • DNA, Neoplasm
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Methotrexate
  • Adult
  • Antimetabolites, Antineoplastic (therapeutic use)
  • DNA, Neoplasm (blood, genetics)
  • Female
  • Gestational Trophoblastic Disease (drug therapy, enzymology, genetics)
  • Humans
  • Methotrexate (therapeutic use)
  • Methylenetetrahydrofolate Reductase (NADPH2) (genetics)
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Pregnancy
  • Young Adult

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