Relationship Between Antimetabolite Toxicity and Pharmacogenetics in Turkish Cancer Patients

Introduction: Antimetabolites may cause severe toxicity and even toxic death in cancer patients. Our aimwas to evaluate the relationship between antimetabolite toxicity and pharmacogenetics in patients with severeclinical toxicity or alanine transaminase (ALT) elevation after fluorouracil (5FU), capecitabine or methotrexateadministration. Patients and
Methods: Cancer patients with severe antimetabolite toxicity were evaluatedfor methylenetetrahydrofolate reductase (MTHFR) gene C667T, thymidilate synthase (TS) gene 5´UTRvariable number of tandem repeats (VNTR), dihydroprymidine dehydrogenase (DPYD) gene IVS14+1G/A,Xeroderma pigmentosum (XPD) gene Lys751Gln and X-ray repair cross-complementing group 1 (XRCC1) geneArg399Gln polymorphisms.
Results: Eighteen patients were enrolled, with a male/female ratio of 0.8. They hadosteosarcoma in methotrexate group (n=7), gastrointestinal malignancies in 5FU group (n=9) and breast cancerin the capecitabine group (n=2). Mucositis and dermatitis occurred in all groups, together with ALT elevationin the methotrexate group and 2 toxic deaths were encountered. DPYD, TS, MTHFR, XPD and XRCC1 genepolymorphism rare allele frequencies were observed to be higher than in the general population.
Conclusion:Pharmacogenetics might contribute to tailored therapy.