Objectives Methotrexate has long been used successfully and is preferred worldwide for the treatment of low-risk gestational trophoblastic neoplasia. However, 26.4% of patients develop resistance and require changes to second-line chemotherapy. In the search for personalised treatment approaches, a link has been found between the pharmacogenomics of methotrexate and the response in various diseases. The aim of this study was to explore the effects of ABCB1 and SCLO1B1 gene polymorphisms and the methotrexate treatment response in patients with low-risk gestational trophoblastic neoplasia. Secondary objectives were to investigate the association of single nucleotide polymorphism (SNP) genotypes with toxicity profiles, and to evaluate other factors associated with the response.
Methods Records of all patients with low-risk gestational trophoblastic neoplasia were reviewed and patients who received methotrexate as a single agent were invited to participate in the study. DNA was extracted from peripheral blood samples from 18 patients and assessed for ABCB1 (3435C>T) and SCLO1B1 (521T>C).
Results For the ABCB1 polymorphism, CT was the most common genotype (61.1%), followed by CC (27.8%) and TT (11.1%), indicating that TT had a 1.6-fold higher risk of methotrexate-resistance when compared to the wild-type and heterozygous alleles. The risk of methotrexate-related toxicity was 2.67-fold higher in CT/CC patients who showed a better response to methotrexate. The SCLO1B1 polymorphism was not associated with treatment outcomes.
Conclusions ABCB1 polymorphism might be useful as a biomarker for predicting the response to methotrexate in patients with low-risk gestational trophoblastic neoplasia.
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