AUTHOR=Atasilp Chalirmporn , Lenavat Rinradee , Vanwong Natchaya , Chansriwong Phichai , Sirachainan Ekaphop , Reungwetwattana Thanyanan , Jinda Pimonpan , Aiempradit Somthawin , Sirilerttrakul Suwannee , Chamnanphon Monpat , Puangpetch Apichaya , Sankuntaw Nipaporn , Satapornpong Patompong , Sukasem Chonlaphat 

TITLE=Effects of polymorphisms in the MTHFR gene on 5-FU hematological toxicity and efficacy in Thai colorectal cancer patients

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.916650

DOI=10.3389/fonc.2022.916650

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>The two common methylenetetrahydrofolate reductase (<italic>MTHFR</italic>) polymorphisms 677G&gt;A and 1298A&gt;C may have been affecting 5-FU toxicity in cancer patients for decades. Drug efficacy has also been shown by previous studies to be affected. In this study, we investigated the effects of these polymorphisms on 5-FU hematological toxicity and treatment efficacy, to provide enhanced pharmacological treatment for cancer patients.</p></sec><sec><title>Methods</title><p>This is a retrospective study involving 52 Thai colorectal cancer patients who were treated with 5-FU based therapy, using TaqMAN real-time PCR to genotype the <italic>MTHFR</italic> polymorphisms (677G&gt;A and 1298A&gt;C). The toxicity and response rate were assessed using standardized measures.</p></sec><sec><title>Results</title><p>Neutropenia was significantly more likely to be experienced (<italic>P</italic>=0.049, OR=7.286, 95% CI=0.697-76.181) by patients with the <italic>MTHFR</italic> 677G&gt;A polymorphism, in the same way as leukopenia (<italic>P</italic> =0.036, OR=3.333, 95%CI=2.183-5.090) and thrombocytopenia (<italic>P</italic>&lt;0.001, OR=3.917, 95%CI=2.404-6.382). The <italic>MTHFR</italic> 1298A&gt;C polymorphism had no statistical association with hematological toxicity in 5-FU treatment. The response rate to 5-FU was not significantly affected by these two polymorphisms.</p></sec><sec><title>Conclusion</title><p>The <italic>MTHFR</italic> polymorphism 677G&gt;A is a significant risk factor for developing leukopenia, neutropenia and thrombocytopenia as toxic effects of 5-FU therapy in cancer patients. Therefore, patients receiving 5-FU-based therapy should be aware of their polymorphisms as one risk factor for experiencing severe toxicity.</p></sec>