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

Abstract：

OBJECTIVE: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. METHODS: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. RESULTS: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. CONCLUSION: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.

journal_name

Gynecol Oncol

journal_title

Gynecologic oncology

authors

Lasecka L,Dixon PH,Molokhia M,Sharma N,Schleh A,Wang CM,Steel JH,Seckl MJ,Savage PM,Fisher RA

doi

10.1016/j.ygyno.2011.08.012

subject

Has Abstract

pub_date

2011-12-01 00:00:00

pages

605-9

issue

eissn

0090-8258

issn

1095-6859

pii

S0090-8258(11)00697-4

journal_volume

123

pub_type

杂志文章

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