Initiation of the Pharmacogenetics of Capecitabine in Morocco

Title:Initiation of the Pharmacogenetics of Capecitabine in Morocco

Volume: 18 Issue: 4

Author(s): Khalid Zouine*, Meryem Abassi, Laila Bouguenouch, Ismail Mouhrach, Kettani Oussama, Souleimani Abdellah, Ouldim Karim and Mellas Nawfel

Affiliation:

• Laboratory of Medical Genetics and Oncogenetics, Central Laboratory of Medical Analysis, CHU Hassan II, Fez, Morocco
• Faculty of Sciences, Dhar El Mahraz, FSDM Sidi Mohamed Ben Abdellah University, Fez City, Morocco

Keywords: Polymorphism, capecitabine, side effects, DPYD, SNPs, chemotherapy.

Abstract:

Introduction: The pharmacogenetics of anticancer drugs is of paramount importance in minimizing their side effects and increasing their efficacy. When applied to capecitabine, the result is that variation in patient responses has been largely linked to different genetic polymorphisms of dihydropyrimidine dehydrogenase (DPD), which explained in many cases, the onset of toxicity of this medication in patients. Failure of this enzyme is known to be responsible for a high incidence of serious or fatal side effects. In this study conducted on Moroccan patients under treatment with capecitabine at usual doses at the Fez University Hospital, the first in Africa and Morocco, we are looking for the presence of four variants of the DPD gene (DPYD): T486A on exon 5 (rs666523971), c.1679T> G (p.I560S; rs55886062; allele DPYD * 13) on exon 13, c.1905 + 1G> A (IVS14 + 1G> A; rs3918290; allele DPYD * 2A) on the splice site near exon 14 and the c.2846A> T mutation (p.D949V; rs67376798) on exon 22. We will therefore seek to establish the cause-and-effect relationship between this toxicity and the presence of these variants in his patients, which will allow us to avoid the dangerous prescription of capecitabine in patients carrying these polymorphisms.

Methods: This prospective study is carried out at the Laboratory of Medical Genetics of the CHU Hassan II Fez and spread over a period of 3 years. Patient recruitment was carried out by the oncology department of CHU Hassan II-Fès. All recruited patients are treated with capecitabine. A total of 64 patients were tested. Blood samples (5 ml) were obtained from each one of them after their consent, and DNA was extracted. The study of these four polymorphisms was carried out by PCR sequencing.

Results and Discussion: We have studied 64 patients taking capecitabine. Their median age was 50, and the mean age was 50 and 79, with extremes of 25 and 78 years. The sex ratio F / M was 0,60.

Different levels of toxicity have been developed in patients ranging from simple vomiting to IVdegree hand and foot syndrome and second-degree neuropathy involving total discontinuation of treatment.

These mutations were not found in the patients. Thus it would be interesting to enlarge the sample size, look for these polymorphisms and others on other exons of the DPYD gene, and try to understand the cause of this increased incidence of capecitabine toxicity in the Moroccan population.

Conclusion: Capecitabine-based chemotherapy caused adverse effects with varying levels in its patients. The SNPs on the DPYD gene sought were not found in this Moroccan sample. It is desirable to screen more patients and to search for other SNPs to understand the toxicity of capecitabine in relation to the DPYD gene. This will make it possible to adjust the dosage of this drug, increase its effectiveness and minimize its toxicity.

Cite this article as:

Zouine Khalid*, Abassi Meryem, Bouguenouch Laila, Mouhrach Ismail, Oussama Kettani, Abdellah Souleimani, Karim Ouldim and Nawfel Mellas, Initiation of the Pharmacogenetics of Capecitabine in Morocco, Current Cancer Therapy Reviews 2022; 18 (4) . https://dx.doi.org/10.2174/1573394718666220803100928