MIR27Ars895819 TC genotype increases risk of fluoropyrimidine-induced severe toxicity independently of DPYDvariations

Aim:MicroRNA 27a (miR-27a) regulates post-transcriptionally DPD activity. We have analyzed the association of MIR27Ars895819T>C variation, that modulates miR-27a expression, with FP-induced toxicity. Materials & methods:MIR27Ars895819T>C genotyping was conducted by TaqMan allelic discrimination assay in 313 FP-treated cancer patients. Results: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 DPYDdeficiency (OR: 8.923; p = 0.006) and MIR27Ars895819 TC genotype (OR: 3.865; p = 0.002). Conclusion:MIR27Ars895819 TC genotype is an independent risk factor for fluoropyrimidine-associated toxicity in the Greek population. Thus, MIR27Ars895819TC patients can be closely monitored for fluoropyrimidine-induced severe toxicity.