Towards Personalized Chemotherapy in Gastrointestinal Cancers: Prospective Analysis of Pharmacogenetic Variants in a Russian Cohort

<b>Background/Objectives</b>: Pharmacogenetic variability plays a crucial role in determining both the efficacy and toxicity of chemotherapy for gastrointestinal cancers. However, data on allele frequencies and their clinical relevance in Russian populations remain scarce. <b>Methods</b>: We conducted a prospective observational study of 412 patients with gastrointestinal malignancies between 2020 and 2023. Pharmacogenetic testing was performed prior to the initiation of chemotherapy using real-time allele-specific PCR and microarray hybridization technology. Polymorphisms in the <i>DPYD, UGT1A1, CYP2C8, CYP3A5, GSTP1, ERCC1, XPC, CDA, MTHFR, TYMS</i>, and <i>SLC31A1</i> genes were analyzed. <b>Results</b>: The frequency of most variants was consistent with those reported in European populations, reflecting the ethnic proximity of the studied cohort. Several clinically relevant variants were identified: <i>DPYD</i> rs2297595 occurred more frequently than in European cohorts, and <i>UGT1A1</i> rs8175347 was observed at a higher prevalence, underscoring the potential risk of irinotecan-related neutropenia and diarrhea. <i>CYP2C8</i> rs10509681 was present at frequencies comparable to European populations and is associated with an increased risk of taxane-induced peripheral neuropathy. Other markers (<i>GSTP1, ERCC1, CDA, SLC31A1, MTHFR, TYMS</i>) demonstrated variable associations with chemotherapy efficacy and toxicity, consistent with findings from previous international studies. <b>Conclusions</b>: This study provides the first comprehensive description of pharmacogenetic polymorphisms in a Russian cohort of patients with gastrointestinal cancers. Our findings confirm the clinical importance of <i>DPYD</i> and <i>UGT1A1</i> testing and highlight additional variants of potential interest.