Étude du génotypage des variants du gène DPYD et leur influence sur le traitement par fluoropyrimidines chez les patients atteints de cancer colorectal

Abstract

Colorectal cancer is one of the leading causes of cancer-related morbidity and mortality worldwide. Fluoropyrimidines, particularly 5-fluorouracil and capecitabine, remain the cornerstone of treatment for this malignancy. However, a subset of patients experiences severe toxicity, often associated with reduced activity of dihydropyrimidine dehydrogenase (DPD), the key enzyme involved in fluoropyrimidine metabolism. This deficiency is mainly linked to genetic variants of the DPYD gene. Therefore, this study aimed to evaluate the frequency of major DPYD gene variants in patients with colorectal cancer and to assess their potential impact on fluoropyrimidine dose individualization. This study included 23 patients diagnosed with colorectal cancer who were treated or scheduled to receive fluoropyrimidine-based chemotherapy. Genotyping was performed for clinically relevant DPYD variants known to be associated with fluoropyrimidine-related toxicity. Genotypic and allelic frequencies were determined and compared with data reported in other populations. The results revealed a predominance of wild-type genotypes for most of the investigated variants, whereas a limited number of patients carried variant alleles. These findings highlight the existence of genetic variability within the studied population and suggest particular characteristics compared with frequencies reported in other ethnic and geographical populations. The findings of this study support the clinical value of DPYD pharmacogenetic screening prior to fluoropyrimidine administration. Identifying patients carrying risk variants enables personalized dose adjustment, thereby reducing the likelihood of severe toxicity and improving treatment safety. Although the sample size was limited, this work provides preliminary data on the distribution of DPYD variants in the Algerian population and emphasizes the importance of integrating personalized medicine into oncology practice. Larger studies are warranted to confirm these findings and further characterize the pharmacogenetic profile of the Algerian population.