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

被引:0
作者
Bukhari, Nedal [1 ,2 ,3 ]
Al-Mohanna, Hani [4 ]
Almsned, Fahad [5 ,6 ]
机构
[1] King Fahad Specialist Hosp, Dept Med Oncol, Dammam, Saudi Arabia
[2] Imam Abdulrahman Bin Faisal Univ, Dept Internal Med, Dammam, Saudi Arabia
[3] Prince Sultan Mil Med City, Dept Med Oncol, Riyadh, Saudi Arabia
[4] King Fahad Specialist Hosp, Dept Epidemiol & Biostat, Dammam, Saudi Arabia
[5] Eastern Hlth Cluster, Dept Populat Hlth Management, Dammam, Saudi Arabia
[6] Novo Genom, Dept Res & Dev, Riyadh, Saudi Arabia
关键词
colon cancer; capecitabine; 5-fluorouracil; thymidylate synthase; methylenetetrahydrofolate reductase; dihydropyrimidine dehydrogenase; 5-FLUOROURACIL; DPYD;
D O I
10.7759/cureus.49215
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
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