Asian Pacific journal of cancer prevention : APJCP · 2012
Relationship between antimetabolite toxicity and pharmacogenetics in Turkish cancer patients.
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Dogan Mutlu, Karabulut Halil G, Tukun Ajlan, Demirkazik Ahmet, Utkan Gungor, Yalcin Bulent, Dincol Dilek, Akbulut Hakan, Icli Fikri
Аннотация
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.
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.
Предметные рубрики MeSH
AdolescentAdultAgedAged, 80 and overAlanine TransaminaseAllelesAntimetabolites, AntineoplasticBone NeoplasmsBreast NeoplasmsCapecitabineDNADNA-Binding ProteinsDeoxycytidineDihydrouracil Dehydrogenase (NADP)Drug EruptionsFemaleFluorouracilGastrointestinal NeoplasmsGene FrequencyHumansMaleMethotrexateMethylenetetrahydrofolate Reductase (NADPH2)Middle AgedMinisatellite RepeatsMucositisOsteosarcomaPolymorphism, GeneticThymidylate SynthaseTurkeyX-ray Repair Cross Complementing Protein 1Xeroderma Pigmentosum Group D ProteinYoung Adult