The Prevalence of UGT1A1*93 and ABCC5 Polymorphisms in Cancer Patients Receiving Irinotecan-Based Chemotherapy at Al-Najaf Al-Ashraf

Abstract

Irinotecan (CPT-11) is a semisynthetic derivative of the antineoplastic agent camptothecin used in a wide range as an anti-cancer agent in many solid tumors because of its cytotoxic effect through the interaction with the topoisomerase I enzyme. The major limiting factors for irinotecan treatment are its association with potentially life-threatening toxicities including neutropenia and acute or delayed-type diarrhea, results from distinct interindividual and interethnic variability due to gene polymorphism.

This is a cross sectional pharmacogentics study was conducted on 25 cancer patients to estimate the prevalence of UGT1A1*93 and ABCC5 allele single nucleotide polymorphism (SNP) in Iraqi cancer patients treated with irinotecan-based therapy at Middle Euphrates Cancer Center. Four drops of venous blood was drawn for each patient and was applied onto the FTA classic card to perform a genotyping assay for the 2 SNPs. After DNA isolation and purification, real time PCR was performed to detect the SNPs of each gene.

Results of this study showed the prevalence of one allele variant (heterozygous mutation) of UGT1A1*93 was 64% compared to 36% of patients were wild type to this SNP. No patient (0%) could be detected with homozygous polymorphism of the UGT1A1*93. For the ABCC5 polymorphism, results revealed that 32% of patients have one polymorphic allele (heterozygous), while 28% of them have two polymorphic alleles (homozygous mutation). Wild type ABCC5 gene constitutes 40% of patients.   As a conclusion, high prevalence of UGT1A1*93 and ABCC5 polymorphic alleles were detected in patients at Middle Euphrates Cancer Center which may explain the high toxicity features associated with irinotecan therapy. 

Received:  20/1 /2019

Accepted: 2/3 /2019