DPYDand TYMSpolymorphisms as predictors of 5 fluorouracil toxicity in colorectal cancer patients

Autor: Khalij, Yassine, Belaid, Imtinen, Chouchane, Sana, Amor, Dorra, Omezzine, Asma, Ben rejeb, Nabila, ben Ahmed, Slim, Bouslama, Ali
Zdroj: Journal of Chemotherapy; July 2023, Vol. 35 Issue: 5 p425-434, 10p
Abstrakt: AbstractColorectal cancer (CRC) is the third most common cancer and the fourth leading cause of cancer death. 5-Fluorouracil (5-FU) is an essential component of systemic chemotherapy for CRC. Our objective was to determine the genotypic frequency of polymorphisms affecting dihydropyrimidine dehydrogenase (DPYD) and thymidylate synthetase (TYMS) genes and to correlate the genetic profile with the toxicity due to 5-FU, also considering nongenetic factors. This is a prospective study that involved 66 patients. We extracted DNA by salting out methods. We carried out the genotyping of the different polymorphisms by simple PCR for the TYMS5'UTR and by PCR-RFLP for DPYD: 1905 + 1 G > A, 85 T > C, 496 A > G, 1679 T > G, c.483 + 18G > A and the TYMS: 5'UTR VNTR, 5'UTR G > C and 3'UTR. The study of the association of DPYDand TYMSpolymorphisms with the various signs of toxicity under 5-FU revealed that the polymorphisms 496 A > G were significantly associated with hepatotoxicity: OR = 3.85(p = 0.04). In addition, 85 T > C was significantly associated with mucositis and neurotoxicity: OR = 4.35(p = 0.03), OR = 3.79(p = 0.02). For TYMS,the only significant association we observed for 5'UTR with vomiting: OR = 3.34(p = 0.04). The incidence of adverse reactions related to 5-FU appears to be influenced in patients with CRC by the identified DPYDand TYMSgene polymorphisms in the Tunisian population.
Databáze: Supplemental Index