Potential application of GSTT1-null genotype in predicting toxicity associated to 5-fluouracil irinotecan and leucovorin regimen in advanced stage colorectal cancer patients
Romero R.Z., Morales R., García F, Huárriz M., Bandrés E., De la Haba J., Gómez A., Aranda E., García-Foncillas J.
Laboratory of Biotechnology and Pharmacogenomics, Center for Applied Medical Research, University Clinic of Navarra, Navarra 31008, Spain
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.
CITA DEL ARTÍCULO Oncol Rep. 2006 Sep;16(3):497-503