Pilot study from Genomics England to report on DPYD variants

A pilot study from Genomics England is now reporting back DPYD variants in cancer patients as part of the 100,000 Genomes Project.

The DPYD protein is responsible for degrading fluoropyrimidine drugs, which include 5-fluorouracil and capecitabine. These drugs are commonly used in the treatment of cancer. Decreased activity of the DPYD protein is associated with an increased risk for severe or fatal toxicity from standard doses of fluoropyrimidine drugs. Guidelines from the Clinical Pharmacogenetics Implementation Consortium (CPIC) recommend reducing the starting dose of fluorouracil and capecitabine in patients with decreased DPYD activity, and avoiding use of the drugs in patients with absent DPYD activity.

For cancer patients recruited into the 100,000 Genomes Project, Genomics England is prospectively analyzing germline whole genome sequence (WGS) data for the presence of the rs3918290 (1905+1G>A; DPYD*2A), rs55886062 (1679T>G; DPYD*13), rs67376798 (2846A>T) and rs56038477/rs75017182 (1236G>A/1129-5923C>G; haplotype B3) variants. rs3918290 and rs55886062 are associated with absent DPYD activity, while rs67376798 and rs56038477/rs75017182 confer decreased DPYD activity. If any of these DPYD variants are discovered in the analysis, the genome analysis report for those variants includes a link out to the PharmGKB website for more information.

The WGS results are made available to Genomic Medicine Centres, allowing clinicians to assess whether adjusting treatment regimens may help reduce toxicity risk. Feedback on any actions taken by clinicians will be recorded and analyzed to determine the clinical effectiveness of reporting these variants within the National Health Service (NHS). The program aims to demonstrate how WGS results can help cancer patients receive effective treatment with a lower risk for severe toxicity.


Read the Genomics England blogpost
Read the CPIC guideline for fluoropyrimidines and DPYD

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