Thymidylate Synthase (TYMS) and Methylenetetrahydrofolate Reductase (MTHFR) Gene Polymorphisms Associated With Severe Capecitabine Toxicity: The First Case From Saudi Arabia

Nedal Bukhari; Hani Al-Mohanna; Fahad Almsned

doi:10.7759/cureus.49215

Thymidylate Synthase (TYMS) and Methylenetetrahydrofolate Reductase (MTHFR) Gene Polymorphisms Associated With Severe Capecitabine Toxicity: The First Case From Saudi Arabia

Cureus. 2023 Nov 22;15(11):e49215. doi: 10.7759/cureus.49215. eCollection 2023 Nov.

Authors

Nedal Bukhari^{1

2

3}, Hani Al-Mohanna⁴, Fahad Almsned^{5

6}

Affiliations

¹ Department of Medical Oncology, King Fahad Specialist Hospital, Dammam, SAU.
² Department of Internal Medicine, Imam Abdulrahman Bin Faisal University, Dammam, SAU.
³ Department of Medical Oncology, Prince Sultan Military Medical City, Riyadh, SAU.
⁴ Department of Epidemiology and Public Health, King Fahad Specialist Hospital, Dammam, SAU.
⁵ Department of Population Health Management, Eastern Health Cluster, Dammam, SAU.
⁶ Department of Research and Development, Novo Genomics, Riyadh, SAU.

Abstract

Dihydropyrimidine dehydrogenase (DPD) is the major enzyme in the catabolism of fluoropyrimidine chemotherapy. Deficiencies in this enzyme level typically predispose patients to fluoropyrimidine toxicities, and they are often linked to DPYD gene polymorphisms. Other gene polymorphisms such as thymidylate synthase (TYMS) and methylenetetrahydrofolate reductase (MTHFR) may induce similar toxicities. We report a patient with resected stage III colon cancer presenting with severe toxicity to adjuvant capecitabine, a prodrug of 5-fluorouracil (5-FU). Her DPYD gene sequencing was normal. However, the patient was heterozygous for c.1298A>C (p.E429A) in the methylenetetrahydrofolate reductase (MTHFR) gene and c.*450_*455del in the thymidylate synthase (TYMS) gene. The capecitabine dose was reduced in subsequent treatments and then titrated up gradually with no major side effects reported.

Keywords: 5-fluorouracil; capecitabine; colon cancer; dihydropyrimidine dehydrogenase; methylenetetrahydrofolate reductase; thymidylate synthase.

Publication types

Case Reports