Investigation of DPYD, MTHFR and TYMS polymorphisms on 5-fluorouracil related toxicities in colorectal cancer

Cevik M., Namal E., Sener N. D., Koksal U. I., Cagatay P., Deliorman G., ...More

PERSONALIZED MEDICINE, vol.19, no.5, pp.435-444, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 19 Issue: 5
  • Publication Date: 2022
  • Doi Number: 10.2217/pme-2021-0047
  • Journal Name: PERSONALIZED MEDICINE
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core, EMBASE, MEDLINE
  • Page Numbers: pp.435-444
  • Keywords: adverse effects, colorectal cancer, DPYD, fluoropyrimidines, MTHFR, pharmacogenetics, polymorphisms, TYMS, DIHYDROPYRIMIDINE DEHYDROGENASE GENE, METHYLENETETRAHYDROFOLATE REDUCTASE, THYMIDYLATE-SYNTHASE, CAPECITABINE, VARIANTS, METABOLISM, EFFICACY, PREDICT, PHARMACOKINETICS, DPYD-ASTERISK-2A
  • Istanbul University Affiliated: No

Abstract

Aim: To investigate the association of DPYD, MTHFR and TYMS polymorphisms on 5-fluorouracil (5-FU) related toxicities and patient survival. Materials & methods: A total of 103 colorectal cancer patients prescribed 5-FU were included in the study. Genotyping was conducted for several DPYD, MTHFR and TYMS polymorphisms using a microarray analyzer. Results: DPYD 496A>G polymorphism was found to be significantly associated with 5-FU related grade 0-2, but not severe toxicities (p = 0.02). Furthermore, patients with DPYD 85TC and CC genotypes had longer progression and overall survival times compared to TT genotypes in our study group (log rank = 6.60, p = 0.01 and log rank = 4.40, p = 0.04, respectively). Conclusion: According to our results, DPYD 496AG and GG genotypes might be protective against severe adverse events compared to the AA genotype. Another DPYD polymorphism, 85T>C, may be useful in colorectal cancer prognosis. Further studies for both polymorphisms should be conducted in larger populations to achieve accurate results.