Rs895819 TC Genotype Increases Risk of Fluoropyrimidine-induced Severe Toxicity Independently of Variations

MicroRNA 27a (miR-27a) regulates post-transcriptionally DPD activity. We have analyzed the association of rs895819T>C variation, that modulates miR-27a expression, with fluropyrimidine-induced toxicity. rs895819T>C genotyping was conducted by TaqMan® allelic discrimination assay in 313 FP-treated cancer patients. In overdominance (TC vs TT + CC), TC genotype was associated with grade 3-4 toxicity (p = 0.002), any grade toxicity (p = 0.052), and delayed drug administration or therapy discontinuation (p = 0.038). Odds of grade 3-4 toxicity were increased by both deficiency (OR: 8.923; p = 0.006) and rs895819 TC genotype (OR: 3.865; p = 0.002). rs895819 TC genotype is an independent risk factor for fluoropyrimidine-associated toxicity in the Greek population. Thus, rs895819TC patients can be closely monitored for fluoropyrimidine-induced severe toxicity.