Variants in the dihydropyrimidine dehydrogenase, methylenetetrahydrofolate reductase and thymidylate synthase genes predict early toxicity of 5-fluorouracil in colorectal cancer patients
| Autor: | MH Kristensen, J Ellehauge, Palle Pedersen, Gitte Vedel Melsen, J Mejer |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Male
Antimetabolites Antineoplastic Colorectal cancer medicine.medical_treatment Pharmacology Adenocarcinoma Biochemistry Thymidylate synthase Predictive Value of Tests Dihydropyrimidine dehydrogenase Medicine Humans Gene Dihydrouracil Dehydrogenase (NADP) Methylenetetrahydrofolate Reductase (NADPH2) Aged Aged 80 and over Chemotherapy Polymorphism Genetic biology business.industry Biochemistry (medical) Cell Biology General Medicine Thymidylate Synthase Middle Aged medicine.disease Fluorouracil Methylenetetrahydrofolate reductase Cancer research biology.protein DPYD Female business Colorectal Neoplasms medicine.drug |
| Zdroj: | The Journal of international medical research. 38(3) |
| ISSN: | 0300-0605 |
| Popis: | Adverse drug reactions to 5-fluorouracil (5-FU)-based chemotherapy have been reported to be due, in part, to genetic variants of the genes for the drug-related enzymes thymidylate synthase (TS; TYMS gene), methylenetetrahydrofolate reductase ( MTHFR gene) and dihydropyrimidine dehydrogenase (DPD; DPYD gene). This study investigated whether selected genetic variants of the TYMS, MTHFR and DPYD genes predict 5-FU-related early toxicity. The prevalence of the genetic variants was determined in 122 colorectal cancer patients and in a reference population of 320 blood donors. Subgroup analysis of 68 of the colorectal cancer patients was carried out to determine the relationship between selected gene variants detected in peripheral mononuclear cells and tolerability during the first or second cycle of 5-FU based treatment. Toxicity was linked to the TYMS 2R/2R variant (relative risk [RR] 1.66; sensitivity 0.37; specificity 0.77) and to the MTHFR c1298 C/C genetic variant (RR 1.77; sensitivity 0.17; specificity 0.91). Patients with the genetic variant IVS14+1 G/A or c1896 C/T in the DPYD gene had a statistically significant increased risk of experiencing toxicity (RR 2 and 6, respectively), both having a high specificity (0.97 and 0.98, respectively) and low sensitivity (0.04 and 0.13, respectively). It is concluded that pre-treatment detection of genetic variants can help to predict early toxicity experienced by patients receiving 5-FU-based chemotherapy. |
| Databáze: | OpenAIRE |
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