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4CPS-084 Genotyping analysis of polymorphisms in the diahydropyrhydromidine dehydrogenase (dpyd) gene prior to administration of fluoropirmidines
  1. A Melgarejo-Ortuño,
  2. MP Bautista Sanz,
  3. CA Apezteguia Fernandez,
  4. E Matilla Garcia,
  5. LE Hoyo Gil,
  6. MA Amor Garcia,
  7. B Rodriguez Vargas,
  8. R Moreno Diaz
  1. Hospital Universitario Infanta Cristina, Pharmacy, Madrid, Spain


Background and Importance It is highly recommended to genotype DPYD gene polymorphisms before administration. Complete deficiency of DPD activity is very rare, estimated at 0.01% to 0.5% of individuals, partial deficiency has been estimated at 3% to 8%.

Aim and Objectives The aims of the study included the description and frequency of DPYD gene polymorphisms prior to fluoropyrimidine administration in all tumour types and the measures taken.

Material and Methods Retrospective, multidisciplinary study in a tertiary hospital, with the participation of pharmacy, clinical analysis and oncology departments, by reviewing the genotyping of DPYD gene polymorphisms. Oncology patients who were genotyped in the period from June 2020 to December 2021 were included. Four DPYD variants were analysed: DPYD*2A, c.2846A>T, c.1679T>G and c.1236G>A(HapB3) and the genotype of 82 polymorphic regions of the DPYD gene related to the level of enzyme activity. Variables recorded: sex, age, tumour location, variant found and degree of enzyme activity (poor metaboliser(0–0.5), intermediate metaboliser(1–1.5) and normal metaboliser(2).

Results A total of 150 patients, 56.7% female, with a median age of 68.9 years(53.2–84.6) were screened. Tumour sites were: colorectal(48.7%), breast(22.7%), gastric(8.7%), pancreatic(8.7%), cholangiocarcinoma(6%), head and neck(2.7%) and others (2.5%). 15 patients(10%) had some degree of enzyme deficiency. 5(30%) of the patients presented an enzyme activity level of 1.5, 8 (53%) presented 1, 1 (6%) presented 0.5 and 1(6%) presented 0. The variants found were: in 6 patients (40%) c.2846A>T, 3(20%) c.1129–5923C>G, 7(46.7%) c.1156G>T(*12), 1 (6.7%)c.1777 G>A, 1(6.7%) c.1905+1G>A, 1(6.7%) c.483+18G>A and 1(6.7%) c.1236G>A. 2(13.3%) of the patients had both alleles with mutated variants. 11(73.3%) of the patients had one variant, 3(20%) had 2 variants and 1(6.7%) had 3 variants affected. Intermediate metabolisers had their dose of fluoropyrimidines reduced by 50% and poor metabolisers were spared the use of fluoropyrimidines.

Conclusion and Relevance The main diagnoses were colon and breast cancer. 10% of patients studied had some degree of enzyme deficiency according to the variants analysed, 8.6% with partial deficiency and 1.3% with complete deficiency. Our population showed a high prevalence of deficiencies in relation to the literature described. This determination allowed dose adjustment of these drugs, which represents an advance in terms of safety, allowing personalised treatments, individualising doses and avoiding toxicities.

Conflict of Interest No conflict of interest.

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