Abstract
The importance of this study was the DPYD genetic polymorphisms have been widely found to be related with 5-FU-induced toxicities. The miRNA expression has been influenced to DPD enzyme activity. Methods: DPYD genotyping was detected by TaqMan real-time PCR. Forty-eight miRNA expression were detected by miRNA array. Clinical data and hematological toxicities were analyzed at the first and second cycles of 5-FU administration in Thai colorectal cancer patients. Results: Seventy-five patients with retrospective study were detected five single nucleotide polymorphisms of DPYD. Results revealed significant findings of neutropenia toxicity occurring in 100% of the patients with homozygous DPYD*9A, 85A>G (G/G) since the first cycle of treatment for both Grade 1-4 and Grade 3-4 toxicities (P = 0.003, P < 0.001 respectively). However, patients carrying homozygous variant GG of DPYD *5, 1627A>G were not related significantly with Grade 1-4 toxicity (P = 0.02). Sixteen patients with prospective study were showed no related between miRNA expression and DPYD polymorphisms. However, results reported that there was trend upregulated and downregulated expression of miRNA between homozygous and heterozygous variants of DPYD*9A, 85A>G and wild type. One overexpressed miRNA and eleven downregulated miRNAs in the mutant compared to the wild-type. Therefore, DPYD*9A, 85A>G should be detected in Thai colorectal cancer patients treated 5-FU for avoiding hematological toxicity.
