Publication: Influence of DPYD gene polymorphisms on 5-Fluorouracil toxicities in Thai colorectal cancer patients
2
0
Issued Date
2025-12-01
Resource Type
ISSN
03445704
eISSN
14320843
Scopus ID
2-s2.0-85211324615
Pubmed ID
39652193
Journal Title
Cancer Chemotherapy and Pharmacology
Volume
95
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Cancer Chemotherapy and Pharmacology Vol.95 No.1 (2025)
Suggested Citation
Atasilp C., Vanwong N., Yodwongjane P., Chansriwong P., Sirachainan E., Reungwetwattana T., Jinda P., Aiempradit S., Sirilerttrakul S., Chamnanphon M., Puangpetch A., Sankuntaw N., Satapornpong P., Fabienne T., Sukasem C. Influence of DPYD gene polymorphisms on 5-Fluorouracil toxicities in Thai colorectal cancer patients. Cancer Chemotherapy and Pharmacology Vol.95 No.1 (2025). doi:10.1007/s00280-024-04722-z Retrieved from: https://hdl.handle.net/20.500.14740/20570
Author's Affiliation
Centre de Recherches en Cancérologie de Toulouse
Ramathibodi Hospital
Chulalongkorn University
Institut Claudius Regaud
Rangsit University
University of Liverpool
Bumrungrad International Hospital
Faculty of Medicine Ramathibodi Hospital, Mahidol University
Thammasat University
Burapha University
Faculty of Medicine, Srinakharinwirot University
Ramathibodi Hospital
Chulalongkorn University
Institut Claudius Regaud
Rangsit University
University of Liverpool
Bumrungrad International Hospital
Faculty of Medicine Ramathibodi Hospital, Mahidol University
Thammasat University
Burapha University
Faculty of Medicine, Srinakharinwirot University
Corresponding Author(s)
Other Contributor(s)
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.