MIR27A rs895819 TC genotype increases risk of fluoropyrimidine-induced severe toxicity independently of DPYD variations.

Abstract

Aim: MicroRNA 27a (miR-27a) regulates post-transcriptionally DPD activity. We have analyzed the association of MIR27A rs895819T>C variation, that modulates miR-27a expression, with fluropyrimidine-induced toxicity. Materials & methods: MIR27A rs895819T>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 DPYD deficiency (OR: 8.923; p=0.006) and MIR27A rs895819 TC genotype (OR: 3.865; p=0.002). Conclusion: MIR27A rs895819 TC genotype is an independent risk factor for fluoropyrimidine-associated toxicity in the Greek population. Thus, MIR27A rs895819TC patients can be closely monitored for fluoropyrimidine-induced severe toxicity.