Génotypage du polymorphisme UGT1A1*28 chez les patients atteints de cancer colorectal traités par l’irinotécan.

Abstract

The UGT1A1 gene encodes the enzyme uridine diphosphate-glucuronosyltransferase 1A1 (UDP-glucuronosyltransferase 1A1), which plays a key role in hepatic detoxification and the metabolism of numerous substances, including irinotecan, a chemotherapeutic agent used in the treatment of metastatic colorectal cancer. The UGT1A1*28 polymorphism may reduce enzymatic activity and alter the metabolism of this drug, leading to variability in therapeutic response and toxicity risk. This study was conducted to determine the frequency of the UGT1A1*28 polymorphism in patients with metastatic colorectal cancer treated with irinotecan. Materials and Methods Genomic DNA was extracted from peripheral blood samples, quantified, and subsequently analyzed by molecular genotyping using real-time polymerase chain reaction (qPCR), enabling the identification of the different genotypes. Results and Discussion Genotypic analysis identified three UGT1A1*28 genotypes: *1/*1, *1/*28, and *28/*28. The *1/*1 genotype was the most frequent 57.1% (; n = 4), followed by *1/28 28.6% ( n = 2) and 28*/*28 14.3% ( n = 1). These findings demonstrate the presence of the UGT1A1*28 polymorphism in the studied population and suggest a notable frequency of the mutant allele, which may have pharmacogenetic implications, particularly regarding the response and tolerance to treatments such as irinotecan. Conclusion In conclusion, the identification of genetic polymorphisms using molecular biology techniques contributes to a better understanding of the biological mechanisms involved in disease. These approaches strengthen the link between biology and medicine by improving disease characterization and supporting the development of personalized therapeutic strategies.

Keywords • Colorectal cancer; Irinotecan; UGT1A1 gene; UGT1A1*28 polymorphism; Genomic DNA extraction; Real-time PCR (qPCR)