氟嘧啶 (FP) 是许多癌症治疗中常用的药物。 EMA 和 FDA 批准的 FP 药物标签建议在治疗开始前对 DPYD*2A (rs3918290)、*13 (rs55886062)、*HapB3 (rs56038477)、等位基因和 DPYD rs67376798 进行基因分型。我们在日常临床常规中实施了 DPYD 基因分型，但我们仍然发现患者对 FP 表现出严重的药物不良事件 (ADE)。我们在这些患者中研究了 DPYD rs1801265、rs17376848、rs1801159、rs1801160、rs1801158 和 rs2297595，作为 FP 相关毒性个体间差异的解释候选，检查与 FP 反应的关联。我们还研究了 DPYD 测试对临床实践中 FP 剂量调整的影响，并表征了我们人群中的 DPYD 基因。我们发现医生完全接受 DPYD 测试得出的治疗建议，并且这种剂量调整不会影响治疗效果。我们还发现，DPYD*4（由 rs1801158 定义）等位基因与单变量（O.R. = 5.66；95% C.I. = 1.35-23.67；p = 0.014）和单变量中较高的 ADE（严重程度≥ 3 级）风险相关。基于 DPYD 基因型对 FP 治疗患者进行多变量分析（OR = 5.73；95% C.I. = 1.41-28.77；p = 0.019）。这使其成为临床实践中实施的候选变体。

Fluoropyrimidines (FPs) are commonly prescribed in many cancer streams. The EMA and FDA-approved drug labels for FPs recommend genotyping the DPYD*2A (rs3918290), *13 (rs55886062), *HapB3 (rs56038477), alleles, and DPYD rs67376798 before treatment starts. We implemented the DPYD genotyping in our daily clinical routine, but we still found patients showing severe adverse drug events (ADEs) to FPs. We studied among these patients the DPYD rs1801265, rs17376848, rs1801159, rs1801160, rs1801158, and rs2297595 as explanatory candidates of the interindividual differences for FP-related toxicities, examining the association with the response to FPs . We also studied the impact of DPYD testing for FP dose tailoring in our clinical practice and characterized the DPYD gene in our population. We found a total acceptance among physicians of therapeutic recommendations translated from the DPYD test, and this dose tailoring does not affect the treatment efficacy. We also found that the DPYD*4 (defined by rs1801158) allele is associated with a higher risk of ADEs (severity grade ≥ 3) in both the univariate (O.R. = 5.66; 95% C.I. = 1.35-23.67; p = 0.014) and multivariate analyses (O.R. = 5.73; 95% C.I. = 1.41-28.77; p = 0.019) among FP-treated patients based on the DPYD genotype. This makes it a candidate variant for implementation in clinical practice.