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http://dx.doi.org/10.7314/APJCP.2012.13.4.1553

Relationship Between Antimetabolite Toxicity and Pharmacogenetics in Turkish Cancer Patients  

Dogan, Mutlu (Dept of Medical Oncology, School of Medicine, Ankara University)
Karabulut, Halil G. (Dept of Medical Genetics, School of Medicine, Ankara University)
Tukun, Ajlan (Dept of Medical Genetics, School of Medicine, Ankara University)
Demirkazik, Ahmet (Dept of Medical Oncology, School of Medicine, Ankara University)
Utkan, Gungor (Dept of Medical Oncology, School of Medicine, Ankara University)
Yalcin, Bulent (Dept of Medical Oncology, School of Medicine, Ankara University)
Dincol, Dilek (Dept of Medical Oncology, School of Medicine, Ankara University)
Akbulut, Hakan (Dept of Medical Oncology, School of Medicine, Ankara University)
Icli, Fikri (Dept of Medical Oncology, School of Medicine, Ankara University)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.13, no.4, 2012 , pp. 1553-1556 More about this Journal
Abstract
Introduction: Antimetabolites may cause severe toxicity and even toxic death in cancer patients. Our aim was to evaluate the relationship between antimetabolite toxicity and pharmacogenetics in patients with severe clinical toxicity or alanine transaminase (ALT) elevation after fluorouracil (5FU), capecitabine or methotrexate administration. Patients and Methods: Cancer patients with severe antimetabolite toxicity were evaluated for methylenetetrahydrofolate reductase (MTHFR) gene C667T, thymidilate synthase (TS) gene 5´UTR variable 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) gene Arg399Gln polymorphisms. Results: Eighteen patients were enrolled, with a male/female ratio of 0.8. They had osteosarcoma in methotrexate group (n=7), gastrointestinal malignancies in 5FU group (n=9) and breast cancer in the capecitabine group (n=2). Mucositis and dermatitis occurred in all groups, together with ALT elevation in the methotrexate group and 2 toxic deaths were encountered. DPYD, TS, MTHFR, XPD and XRCC1 gene polymorphism rare allele frequencies were observed to be higher than in the general population. Conclusion: Pharmacogenetics might contribute to tailored therapy.
Keywords
Pharmacogenetics; antimetabolite toxicity; methotrexate; fluorouracil;
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