D'Amato M, Iengo G, Massa N, Carlomagno C. Dihydropyrimidine dehydrogenase polymorphisms in patients with gastrointestinal malignancies and their impact on fluoropyrimidine tolerability: Experience from a single Italian institution. World J Gastrointest Oncol 2025; 17(1): 96822 [DOI: 10.4251/wjgo.v17.i1.96822]
Corresponding Author of This Article
Mariarosaria D'Amato, MD, Doctor, Department of Oncology, Ospedale San Rocco ASL Caserta, Via XXI Luglio, Sessa Aurunca 81037, Campania, Italy. mariar.damato@gmail.com
Research Domain of This Article
Oncology
Article-Type of This Article
Retrospective Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastrointest Oncol. Jan 15, 2025; 17(1): 96822 Published online Jan 15, 2025. doi: 10.4251/wjgo.v17.i1.96822
Dihydropyrimidine dehydrogenase polymorphisms in patients with gastrointestinal malignancies and their impact on fluoropyrimidine tolerability: Experience from a single Italian institution
Mariarosaria D'Amato, Department of Oncology, Ospedale San Rocco ASL Caserta, Sessa Aurunca 81037, Campania, Italy
Gennaro Iengo, Nicola Massa, Chiara Carlomagno, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples 80131, Campania, Italy
Author contributions: D’Amato M and Carlomagno C participated in the conception and design of the study, analyzed the data, and wrote the original manuscript; D’Amato M collected the data; D’Amato M, Iengo G, Massa N, and Carlomagno C critically reviewed and provided final approval of the manuscript; D’Amato M, Iengo G, Massa N, and Carlomagno C were responsible for the decision to submit the manuscript for publication.
Institutional review board statement: The investigation was approved by the panel of scientists proposing the research and by all the collaborators who participated in the research.
Informed consent statement: The need for patient consent was waived due to the retrospective nature of the study.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Mariarosaria D'Amato, MD, Doctor, Department of Oncology, Ospedale San Rocco ASL Caserta, Via XXI Luglio, Sessa Aurunca 81037, Campania, Italy. mariar.damato@gmail.com
Received: May 15, 2024 Revised: August 14, 2024 Accepted: August 28, 2024 Published online: January 15, 2025 Processing time: 210 Days and 15.5 Hours
Abstract
BACKGROUND
Fluoropyrimidines are metabolized in the liver by the enzyme dihydropyrimidine dehydrogenase (DPD), encoded by the DPYD gene. About 7% of the European population is a carrier of DPYD gene polymorphisms associated with reduced DPD enzyme activity.
AIM
To assess the prevalence of DPYD polymorphisms and their impact on fluoropyrimidine tolerability in Italian patients with gastrointestinal malignancies.
METHODS
A total of 300 consecutive patients with a diagnosis of gastrointestinal malignancy and treated with a fluoropyrimidine-based regimen were included in the analysis and divided into two cohorts: (1) 149 patients who started fluoropyrimidines after DPYD testing; and (2) 151 patients treated without DPYD testing. Among the patients in cohort A, 15% tested only the DPYD2A polymorphism, 19% tested four polymorphisms (DPYD2A, HapB3, c.2846A>T, and DPYD13), and 66% tested five polymorphisms including DPYD6.
RESULTS
Overall, 14.8% of patients were found to be carriers of a DPYD variant, the most common being DPYD6 (12.1%). Patients in cohort A reported ≥ G3 toxicities (P = 0.00098), particularly fewer nonhematological toxicities (P = 0.0028) compared with cohort B, whereas there was no statistically significant difference between the two cohorts in hematological toxicities (P = 0.6944). Significantly fewer chemotherapy dose reductions (P = 0.00002) were observed in cohort A compared to cohort B, whereas there was no statistically significant differences in chemotherapy delay.
CONCLUSION
Although this study had a limited sample size, it provides additional information on the prevalence of DPYD polymorphisms in the Italian population and highlights the role of pharmacogenetic testing to prevent severe toxicity.
Core Tip: In this retrospective study, we report the prevalence of DPYD polymorphisms in a real-world population of patients treated for gastrointestinal malignancies and their impact on fluoropyrimidine tolerability. Furthermore, we demonstrate that the presence of polymorphisms in the DPYD gene, which encodes dihydropyrimidine dehydrogenase, leads to an increased risk of G3/G4 nonhematologic toxicity and more frequent dose reductions. We did not find a significant difference in chemotherapy delay.
