Abstract 525P
Background
Irinotecan is a cornerstone therapy along with 5 fluorouracil in the management of different gastrointestinal tumors at different stages of disease. The UGT1A1*28 polymorphism, characterized by a seven repeat TA allele (TA7) in the UGT1A1 gene, plays a significant role in the toxicity of irinotecan in gastrointestinal cancer treatment. This polymorphism has been associated with Gilbert syndrome. However, the clinical significance of the UGT1A1*28 polymorphism is still a subject of ongoing research, with conflicting interpretations of pathogenicity and impact reported. This study is the first to explore the frequency of this polymorphism in the general Omani population and provides valuable insights into personalized medicine in oncology.
Methods
We performed a direct sequencing analysis of the UGT1A1 (TA) promoter region in a cohort of 109 unrelated healthy Omani individuals from various geographic regions.
Results
The observed genotypes frequencies were: wild type TA6/TA6 (n=58, 53%) and heterozygous mutant: TA6/TA7 (n=44, 40%), TA5/TA6 (n=2, 1.8%), TA5/TA7 (n=2, 1.8%) & TA6/TA8 (n=3, 2.8%). Our results show the presence of UGT1A1*28 (TA7) allele in the healthy Omani population, along with the less common TA5 and TA8 allele. Other studied populations showed a wild type frequency of 74%.
Conclusions
Testing for UGT1A1 polymorphism is not standard in international guidelines. Identification of UGT1A1 promoter polymorphisms especially UGT1A1*28, emphasizes the importance of genotyping UGT1A1 in Omani GI cancer patients before initiating irinotecan therapy in front of the increased vulnerability of patients and the high incidence of encountered side effects. This approach is crucial to optimizing the effectiveness and safety of the treatment of cancer in Oman. Further studies on actual patient taking irinotecan based therapy with toxicity analysis will follow.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.