Allelic Frequency of DPYD Genetic Variants in Patients With Cancer in Spain: The PhotoDPYD Study
Authors: Miarons Marta , Manzaneque Gordón Alba , Riera Pau , Gutiérrez Nicolás Fernando ,   in Collaboration with the RedDPYD Research Group with the Spanish Society of Hospital Pharmacy (SEFH), Abdel-Kader Martin Laila , Agustín María José , Alcacera López Mª Aranzazu , Alonso Castañé Maria Dolores , Álvarez Martín Tamara , Beloqui Juan José , Bernal Noguera Sara , Burgos San José Amparo , Cachafeiro Pin Ana Isabel , Castellote Belles Laura , Conde-Estévez David , Corrales Paz Marina , Díez García Marc , Do Pazo Oubiña Fernando , Fernández Fradejas Jorge , Frias Ruíz Pau , García González Xandra , Gilabert Sotoca Marta , González Suárez Silvia , Heredia Diana , Hernández Guío Ana , Herranz Muñoz Clara , Ibáñez Collado Cristina , Jiménez Pichardo Lucía , López Aspiroz Elena , López Ferández Luis , Luque Jiménez María , Martínez Bautista María José , Megías Vericat Juan Eduardo , Melgarejo Ortuño Alejandra , Monge Inés , Morales Barrios Alberto , Moreno María , Mourani Padrón Ivette , Pampín Sánchez Ruben , Planas Giner Albert , Porta Oltra Begoña , Prado Mel Elena , Ramos Díaz Ruth , Riestra Ayora Ana , Rodríguez Moreta Claudia , Santiago Pérez Alejandro , Tamayo Bermejo Rocío , Vuelta Arce María 
Published: April 2023

Abstract

Introduction
Identifying polymorphisms in the dihydropyrimidine dehydrogenase (DPYD) gene is gaining importance to be able to predict fluoropyrimidine-associated toxicity. The aim of this project was to describe the frequency of the DPYD variants DPYD*2A (rs3918290); c.1679T&gt;G (rs55886062); c.2846A&gt;T (rs67376798) and c.1129-5923C&gt;G (rs75017182; HapB3) in the Spanish oncological patients.

Material and Methods
Cross-sectional and multicentric study (PhotoDPYD study) conducted in hospitals located in Spain designed to register the frequency of the most relevant DPYD genetic variants in oncological patients. All oncological patients with DPYD genotype were recruited in the participant hospitals. The measures determined where the presence or not of the 4 DPYD previously described variants.

Results
Blood samples from 8054 patients with cancer from 40 different hospitals were used to determine the prevalence of the 4 variants located in the DPYD gene. The frequency of carriers of one defective DPYD variant was 4.9%. The most frequently identified variant was c.1129-5923C&gt;G (rs75017182) (HapB3), in 2.9%, followed by c.2846A&gt;T (rs67376798) in 1.4%, c.1905 + 1G&gt;A (rs3918290, DPYD*2A) in 0.7% and c.1679T&gt;G (rs55886062) in 0.2% of the patients. Only 7 patients (0.08%) were carrying the c.1129-5923C&gt;G (rs75017182) (HapB3) variant, 3 (0.04%) the c.1905 + 1G&gt;A (rs3918290, DPYD*2A) and one (0.01%) the DPYD c.2846A&gt;T (rs67376798, p.D949V) variant in homozygosis. Moreover, 0.07% were compound heterozygous patients, 3 carrying the DPYD variants DPYD*2A + c.2846A&gt;T, 2 the DPYD c.1129-5923C&gt;G + c.2846A&gt;T and one the DPYD*2A + c.1129-5923C&gt;G variants.

Conclusions
Our results demonstrate the relatively high frequency of DPYD genetic variants in the Spanish patient with cancer population, which highlights the relevance of their determination before initiating a fluoropirimidine-containing regimen.