Investigation of Potentially Deleterious Alleles for Response to Cancer Treatment with 5-Fluorouracil

Anticancer Res. 2015 Dec;35(12):6971-7.

Abstract

Aim: To investigate polymorphisms that are probable indicators of response variability during cancer treatment with 5-fluorouracil (rs16430, rs2279198, rs1801159 and rs17878362).

Materials and methods: We investigated 1,038 individuals regarding allele distribution from different populations, out of which we genotyped 127 individuals from a Brazilian admixed population. Similarity analyses with parental populations were performed. Prevalence of potentially deleterious alleles was also evaluated.

Results: Thirty-seven percent of the population had at least three potentially deleterious alleles and 38.6% had at least one potentially deleterious allele in homozygosis.

Conclusion: Potentially deleterious alleles are present under diverse frequencies in different populations. Therefore, genotyping prior to 5-fluorouracil administration should be recommended.

Keywords: 5-fluorouracil; Chemotherapy toxicity; DPYD; OPRT; TP53; TYMS; deleterious alleles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Antineoplastic Agents / adverse effects*
  • Asian People
  • Black People
  • Brazil
  • Dihydrouracil Dehydrogenase (NADP) / genetics*
  • Female
  • Fluorouracil / adverse effects*
  • Gene Frequency
  • Humans
  • Male
  • Multienzyme Complexes / genetics*
  • Neoplasms / drug therapy*
  • Neoplasms / ethnology
  • Neoplasms / genetics
  • Orotate Phosphoribosyltransferase / genetics*
  • Orotidine-5'-Phosphate Decarboxylase / genetics*
  • Polymorphism, Genetic
  • Thymidylate Synthase / genetics*
  • Tumor Suppressor Protein p53 / genetics*
  • White People

Substances

  • Antineoplastic Agents
  • Multienzyme Complexes
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • uridine 5'-monophosphate synthase
  • Dihydrouracil Dehydrogenase (NADP)
  • TYMS protein, human
  • Thymidylate Synthase
  • Orotate Phosphoribosyltransferase
  • Orotidine-5'-Phosphate Decarboxylase
  • Fluorouracil