Uridine diphosphoglucuronosyl transferase and methylenetetrahydrofolate reductase polymorphisms as genomic predictors of toxicity and response to irinotecan-, antifolate- and fluoropyrimidine-based chemotherapy.
Pharmacogenetics could be a useful tool for performing tailored anticancer chemotherapy. Several polymorphisms potentially affecting enzymes responsible for metabolism, transport and mechanism of action of irinotecan, fluoropyrimidines and antifolate agents have been investigated and sometimes associated with toxicity and response. In particular, uridine diphosphoglucuronosyl transferase 1A1 (UGT1A1) enzyme is responsible for detoxification of irinotecan active metabolite, SN38. A polymorphic structure in the promoter region (UGT1A1*28) may affect irinotecan toxicity and SN38 plasma level. Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in the folate cycle, presenting two common polymorphisms (677C>T and 1298 A>C) which have impact on toxicity and efficacy of methotrexate and 5-fluorouracil.
Toffoli
G
G
Experimental and Clinical Pharmacology, CRO - National Cancer Institute, Via Pedemontana Occidentale 12, 33081 Aviano, Italy. gtoffoli@cro.it
Cecchin
E
E
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D012680:Sensitivity and Specificity; D043922:Toxicogenetics; D000099148:UGT1A1 Enzyme
D002166:Camptothecin; D005472:Fluorouracil; D014453:Glucuronosyltransferase; D000077146:Irinotecan; D008727:Methotrexate; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D000099148:UGT1A1 Enzyme