Influence of DPYD gene polymorphisms on 5-Fluorouracil toxicities in Thai colorectal cancer patients.

Abstract

DPYD polymorphisms have been widely found to be related to 5-FU-induced toxicities. The aim of this study was to establish significant associations between five single-nucleotide polymorphisms of DPYD and 5-FU hematological toxicities in Thai colorectal cancer patients. The toxicities were analyzed at the first and second cycles of 5-FU administration in 75 patients. Genotyping was performed using TaqMan real-time PCR. The genotype frequencies of DPYD*2A,1905 + 1 G > A and DPYD 1774 C > T were all wild type. The frequencies of genetic testing for DPYD*5, 1627 A > G, DPYD 1896T > C, and DPYD*9A, 85 A > G were 37.30% (AG; 34.60%, GG; 2.70%), 32.00% (TC; 25.30%, CC; 6.70%), and 13.40% (AG; 10.70%, GG; 2.70%), respectively. The results reveal significant findings with neutropenia occurring in 100% (2/2) of the patients with homozygous variant DPYD*9A (GG) from the first cycle of treatment for both Grade 1-4 and Grade 3-4 toxicities (P = 0.003 and P < 0.001 respectively). DPYD *9A was related to Grade 1-4 leukopenia (P = 0.001) and both Grade 1-4 and severe thrombocytopenia (P < 0.001 and P < 0.001) in the first cycle. In the second cycle, DPYD*5 was shown to be closely associated with no Grade 1-4 toxicity (P = 0.02). However, we found that 100% (2/2) of patients carrying the homozygous variant (GG) DPYD*5, presented no significant toxicity, so, DPYD*5 may be a predictive marker of neutropenia in patients treated with 5-FU. These outcomes suggest that there may be an increased risk of developing 5-FU-induced neutropenia in patients carrying the DPYD*9A, which should be considered as part of the standard procedure.