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Poster Display session 2

3425 - Feasibility and impact of prospective DPYD screening in the Irish population

Date

29 Sep 2019

Session

Poster Display session 2

Topics

Tumour Site

Colon and Rectal Cancer

Presenters

Mohammed Zameer

Citation

Annals of Oncology (2019) 30 (suppl_5): v198-v252. 10.1093/annonc/mdz246

Authors

M.Z. Zameer1, S. iqbal2, B. macanovic2, D. bracken clarke2, C. joyce2, S. O'Reilly1, R.M. Bambury3, D. Power2, D.C. Collins4

Author affiliations

  • 1 Medical Oncology, Cork University Hospital, 0000 - Cork/IE
  • 2 Medical Oncology, Cork University Hospital, 0000 - cork/IE
  • 3 Medical Oncology, Cork University Hospital, Cork/IE
  • 4 Department Of Medical Oncology, Cork University Hospital, Cork/IE

Resources

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Abstract 3425

Background

Genetic variants of dihydropyrimidine dehydrogenase (DPYD) gene can result in varied enzymatic activity and potential toxicity when receiving 5-FU chemotherapy including treatment related death in up to 1% patients. Current international guidelines suggest an international rate of 3-5% albeit routine prospective pharmacogenomic testing is not currently recommended. However, in a genetically homogenous population such as Ireland, DPYD variant enrichment may support routine testing.

Methods

All patients receiving 5-FU based chemotherapy in South & South-West region of Ireland were prospectively tested from 01/09/2018 to present. The Viapath DPYD genotyping panel which interrogates for 5 variants was used. Toxicity type and grade for all patients were recorded (CTCAE v5.0).

Results

To date, 139 patients have been tested,50.4% male and 49.6% female, median age 63 years. The majority(59%) were being treated for colorectal cancer. Sixteen patients were found to be heterozygous carriers of a DYPD variant with one compound heterozygous variant identified i.e. an overall prevalence of 12 %. No homozygous carriers were identified. Grade ≥3 was observed in 33% DPYD variant carriers compared to 19% in DPYD wild type patients i.e. relative risk of grade ≥3 toxicity is 1.7, p = 0.17.Table:

648P

DPYD VariantsPrevalence % n = 139% Rate of ≥ G3 toxicity
7(5.0%)42%
c. 2846A>T1(0.7%)n/a*
c. 1905 + 1G>A3(2.2%)100%
c. 1679T>G0 (0%)n/a*
c. 1601GA5 (3.6%)0%
c. 1905 + 1G>A+c;1236G>A/Hapb3 compound heterozygous1(0.7%)n/a*
TOTAL:17 (12.2%)

Conclusions

The study shows a higher than expected prevalence of DPYD variants of 12.2% compared to internationally reported 3-5%. Patients with DPYD variants c.1236G>A and c.1905+1G>A were particularly likely to develop Grade ≥ 3 toxicity. Prospective testing continues to assess the clinical relevance of individual variants in our population.

Legal entity responsible for the study: The authors.

Clinical trial identification

Editorial acknowledgement

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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