Diversity of oncopharmacogenetic profile within Spanish population

Area of Science:

• Pharmacogenomics
• Clinical Chemistry
• Oncology

Background:

• Established guidelines recommend genotype-guided fluoropyrimidine dosing to mitigate severe toxicity.
• Dihydropyrimidine dehydrogenase (DPYD) gene variations significantly impact drug metabolism and patient outcomes.
• Understanding allelic distribution is crucial for safe and effective antineoplastic drug prescription.

Purpose of the Study:

• To characterize the allelic distribution of specific DPYD and UGT1A1 variants.
• To provide essential pharmacogenetic data for irinotecan and fluoropyrimidine therapy management.
• To assess variant frequencies in Valencian, Aragonese, and Western Andalusian populations.

Main Methods:

• Genotyping of UGT1A1*28 (rs3064744) and DPYD variants (DPYD*2A, c.1679T>G, c.2846A>T, c.1129-5923C>G).
• Analysis of a cohort of 5251 patients undergoing treatment with irinotecan and fluoropyrimidines.
• Population-based allelic frequency determination.

Main Results:

• Detailed allelic distribution data for UGT1A1*28 and multiple DPYD variants were obtained.
• Frequencies were determined in a large patient cohort representative of specific Spanish populations.
• The study provides a precise description of variant frequencies relevant to clinical practice.

Conclusions:

• The allelic distribution data are vital for optimizing genotype-guided dosing of irinotecan and fluoropyrimidines.
• This pharmacogenetic information supports the prevention of serious adverse drug reactions.
• The findings contribute to personalized medicine approaches in cancer treatment.