Abstract 6829: Allele frequency of DPYD genetic variants for fluoropyrimidines metabolism in a Northeast Mexican population
Authors: María L. Garza-Rodríguez, Francisco J. Villarreal-Alvarado, Axa N. Vega-García, Valeria J. Gómez-Ordaz, Irasema Martínez-Ramos, Vanessa N. Ortiz-Murillo, Azalea E. Urdiales-Ordoñez, Alan Burguete-Torres, Fernando Alcorta-Nuñez, Carlos H. Burciaga-Flores, Moisés González-Escamilla, Oscar Vidal-Gutiérrez, Diana C. Pérez-Ibave
Journal: Cancer Research (2025)

Abstract Background: Fluoropyrimidine-based (FP) chemotherapy is used to treat solid cancers, including colorectal and breast cancer. The dihydropyrimidinedehydrogenase (DPD) enzyme is in charge of the metabolism of FP; this enzyme is coded by the dihydropyrimidine dehydrogenase (DPYD) gene. Genetic variants inDPYD have been related to an increased risk of severe toxicity. FP toxicity affects about 30-40% of patients, which in some cases may be lethal. DPYD genotyping aims to identify variants that lead to DPD deficiency. The allele frequency of most of theDPYD variants in the Mexican population is currently unknown. Variant identification in the Mexican population can help oncologists in the treatment of patients by reducing the chances of toxicity by adjusting treatment without comprising the antitumoral activity. The aim was to describe the frequency DPYD gene variants associated with FP toxicity in northeastern Mexico's oncologic population. Methods: We analyzed seven DPYD variants by real-time PCR and Sanger sequencing. Two related to reduced activity (c.1129-5923C-&amp;gt;G and c.2846A-&amp;gt;T)associated with increased risk for toxicity, and four with null activity (c.1156G-&amp;gt;T, c.1905+1G-&amp;gt;A, c.1679T-&amp;gt;G, c.1898delC, and c.299_302delTCAT) with a higher and severe risk for toxicity. Genomic DNA was isolated from 361 subjects: 117 cancer patients and 244 non-cancer subjects. Allele frequency was calculated for each variant and correlated with clinical data. Results: We analyzed a total of 361 subjects, including 117 cancer patients, of which68% had an oncological diagnosis of colorectal cancer, followed by breast cancer with 14%. Metastasic and clinical stage III were present in 42% and 34%, respectively. Grade III (G3) gastrointestinal toxicity was the most common, with a presence of31.9%. The variant c.1129-5923 C&amp;gt;G was found in the heterozygous state in 1.2295%(n=3) of non-cancer patients, the c.2846 A&amp;gt;T variant was found in one non-cancer patient 0.4098% (n=1), and in a 1.7094% (n=2) of cancer patients. The rest of the variants were found in a state of native homozygosity. The two patients carrying the c.2846A&amp;gt;T variant presented a G3 and G4 respectively; one patient required dose adjustment, and the other patient suspended the FP treatment. Conclusions: The allele frequency for two of the seven analyzed variants (c.1129-5923C&amp;gt;G, and c.2846A&amp;gt;T) was higher than reported for the global population (0.00476and 0.005166). DPYD genotyping may help to identify people who are at higher risk of developing severe FP toxicity. Personalized medicine allows oncologists to modify the treatment before it begins. Citation Format: María L. Garza-Rodríguez, Francisco J. Villarreal-Alvarado, Axa N. Vega-García, Valeria J. Gómez-Ordaz, Irasema Martínez-Ramos, Vanessa N. Ortiz-Murillo, Azalea E. Urdiales-Ordoñez, Alan Burguete-Torres, Fernando Alcorta-Nuñez, Carlos H. Burciaga-Flores, Moisés González-Escamilla, Oscar Vidal-Gutiérrez, Diana C. Pérez-Ibave. Allele frequency of DPYD genetic variants for fluoropyrimidines metabolism in a Northeast Mexican population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6829.