Karan Rai1, Gabriel Brooks2,3. 1. Geisel School of Medicine at Dartmouth, Lebanon, NH, USA. 2. The Dartmouth Institute for Health Policy and Clinical Practice, Geisel School of Medicine, Lebanon, NH, USA. 3. Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA.
We agree with Dr. Morelli and colleagues[1] that logistical challenges are a significant obstacle to wider
implementation of DPYD genotyping prior to fluoropyrimidine chemotherapy. We
applaud these authors for this interesting demonstration that normal (non-malignant) tissue
collected during biopsy or resection of cancer can be used as a DNA source for
DPYD genotyping. This tissue-based approach could serve as a complement to
blood-based sample collection in selected circumstances. Another approach that would reduce
barriers to acquisition of timely DPYD genotype information is widespread
implementation of pharmacogenomics in primary care, upstream of a cancer diagnosis.[2]In closing, we note that the DPYD c.2194G>A variant, 1 of 5 variants
evaluated by Dr. Morelli and colleagues, is not recognized by the Clinical Pharmacogenetics
Implementation Consortium (CPIC) as having an association with reduced DPD enzyme function.
CPIC assigns this gene variant as having an activity value of 1 (normal function), which may
partly explain the lack of toxicity with this variant in this cohort.