title: Potential application of GSTT1-null genotype in predicting toxicity associated to 5-fluouracil irinotecan and leucovorin regimen in advanced stage colorectal cancer patients.
abstract: Our aim was to evaluate the role of C-69T in GSTA1, Ile105Val in GSTP1, null allele in GSTT1 and GSTM1 in the prediction of toxicity in patients treated with 5-Fu/CPT-11/Lv regimens in metastatic CRC patients. Fifty-one patients with CRC metastatic disease were analysed. All patients had bidimensionally measurable disease according to WHO criteria. The gender distribution was 37 (74%) males and 13 (26%) females; age ranged from 41 to 71 years; performance status was in all patients > or = 80 (Karnofsky index). The analysis of gene polymorphism was performed in lymphocytes by using PCR-RFLP (GSTA1, GSTP1), PCR (GSTT1, GSTM1) and sequencing analysis (UGT1A1 *28). An appreciable significant association was observed between the GSTT1-null and toxicity: 57% developed gastrointestinal toxicity grade III versus 23% of patients with GSTT1-present genotype (p = 0.053). The other polymorphisms analysed did not show any significant relation with toxicity. Our data suggest that GSTT1-null is associated with a greater probability of developing toxicity to 5-Fu/CPT-11/Lv treatments, indicating a potential application of this genetic analysis in predicting adverse effects of this regimen.
authors.affiliation: Laboratory of Biotechnology and Pharmacogenomics, Center for Applied Medical Research, University Clinic of Navarra, Navarra 31008, Spain. rzarate@unav.es
authors.forename: R Zárate
authors.initials: RZ
authors.lastname: Romero
authors.forename: R
authors.initials: R
authors.lastname: Morales
authors.forename: F
authors.initials: F
authors.lastname: Garcia
authors.forename: M
authors.initials: M
authors.lastname: Huarriz
authors.forename: E
authors.initials: E
authors.lastname: Bandres
authors.forename: J
authors.initials: J
authors.lastname: De la Haba
authors.forename: A
authors.initials: A
authors.lastname: Gómez
authors.forename: E
authors.initials: E
authors.lastname: Aranda
authors.forename: J
authors.initials: J
authors.lastname: García-Foncillas
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000633:toxicity*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000556:secondary; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D000077146:Irinotecan; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin