eP107: Accurate genotyping of UGT1A1 dinucleotide repeat polymorphism from targeted NGS data for the assessment of irinotecan chemotherapy adverse events

Colorectal cancer (CRC) is a leading cause of cancer-related death across the world. Irinotecan (IRI) is commonly used to treat metastatic CRC. The gene UGT1A1 encodes the enzyme responsible for the glucuronidation of SN-38, the active metabolite of IRI. Wild-type UGT1A1 contains six TA repeats [A(TA)6TAA] in its promoter region (also known as the *1 allele). Polymorphic UGT1A1 alleles with a higher number of TA repeats, such as UGT1A1 *28/(TA)7 and *37/(TA)8 alleles, cause decreased enzyme activity and are associated with severe toxicity in patients receiving IRI-based chemotherapy, for which dose reductions are recommended.