[A prevalent genetic variety of UDP-glycuronosyl transferase predicts high risk of irinotecan toxicity].
The advances in genetics and molecular biology have raised new areas in medicine, such as pharmacogenomics, which tries to predict drug responses and toxicities based on the individual genetic variability, describing the so called: pharmacogenomic syndromes. Oncology would find this development extremely useful because of the severe toxicity of chemotherapy. There are a lot of genetic loci under investigation for their potential in predicting drug toxicity, but only three of them have showed clinical usefulness up to now. In particular, quantification of the number of thymine-adenine (TA) dinucleotics in the promoter region of the UDP-glucuronosyl-transferase 1A1 enzime (TA indel) proved to be capable of predicting severe neutropenia in patients exposed to intermediate or high doses of irinotecan. Herein we report a case of a patient with small cell lung cancer who suffered severe hematological and gastrointestinal toxicity after being treated with relatively low doses (65 mg/m(2)) of irinotecan and whose leucocyte DNA analysis showed the presence of seven TA repetitions in both alleles. This case is an example of the clinical applicability and the utility of the test as a toxicity predictor. We also discuss the clinical decisions that may be taken with these patients.
Valsecchi
Matias
M
Laboratorio de Biología y Patología Molecular Universidad de Buenos Aires, Argentina. meval78@yahoo.com
Garberi
Juan
J
Ferrandini
Silvia
S
Berenguer
Roxana
R
Trini
Ernesto
E
Politi
Pedro
P
D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D018288:Carcinoma, Small Cell / Q000188:drug therapy*; D005260:Female; D005819:Genetic Markers / Q000187:drug effects / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics*; D014453:Glucuronosyltransferase / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy*; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced* / Q000235:genetics; D012306:Risk; D000099148:UGT1A1 Enzyme
D000972:Antineoplastic Agents, Phytogenic; D002166:Camptothecin; D005819:Genetic Markers; D014453:Glucuronosyltransferase; D000077146:Irinotecan; D000099148:UGT1A1 Enzyme