Association of Cytidine Deaminase Polymorphism with Capecitabine Effectiveness in Breast Cancer Patients

Aldeen Majeed, Ali Amal; Salih Sahib, Ahmed; Shakir Mahmood, Hasanian; Kadhim Mohsin, Karar; Fadhl Abbas, Raaid

doi:10.31557/APJCP.2023.24.12.4219

Association of Cytidine Deaminase Polymorphism with Capecitabine Effectiveness in Breast Cancer Patients

Document Type : Research Articles

Authors

¹ Department of Pharmacology and Toxicology, College of Pharmacy, University of Kerbala, Iraq.

² Department of Pharmaceutics, College of Pharmacy, University of Alkafeel, Najaf, Iraq.

³ Oncology Center, Al-Hussein Medical City, Kerbala Health Directorates, Kerbala, Iraq.

10.31557/APJCP.2023.24.12.4219

Abstract

Objective: Cancer is caused by abnormal growth and disruption of homeostatic mechanisms. Breast cancer is a major health problem and the second leading cause of death in women. Capecitabine is a prodrug of 5-fluorouracil, which is a non-cytotoxic agent and is used to treat advanced or metastatic breast cancer. Cytidine deaminase (CDA) plays an important role in the activation of capecitabine by acetylating 5-deoxycytidine in the liver, which ultimately leads to the formation of 5-fluorouracil. In this study, we aimed to investigate the relationship between cytidine deaminase polymorphism and capecitabine efficacy in breast cancer patients. Methods: One hundred breast cancer patients aged 45 to 75 years were included in this study, all of whom received capecitabine as monotherapy. The serum levels of CA15.3, calcium, and estradiol E2 in breast cancer patients were investigated. In addition, the relationship of these markers with cytidine deaminase polymorphism was investigated in order to show the association of cytidine deaminase polymorphism with capecitabine efficacy in breast cancer patients. Result: The findings of this study showed that there is a statistically significant relationship between CDA enzyme polymorphisms (rs2072671 and rs532545) with estradiol and CA15.3 serum levels and a non-significant relationship with calcium level. Furthermore, patients who participated were highly polymorphic and heterozygotes genotypes had the highest frequency in both rs2072671 and rs532545 polymorphisms. Conclusion: The results obtained from the present study identified different genetic polymorphisms in the gene encoding the CDA enzyme. Overall, our results clearly showed direct evidence for the association of cytidine deaminase polymorphism with the efficacy of capecitabine in breast cancer patients, which could be useful in reducing side effects and improving drug response to capecitabine.

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