Photo Credit: Katy L. Pack
The following is a summary of “Large-Scale Pharmacogenomics Analysis of Patients With Cancer Within the 100,000 Genomes Project Combining Whole-Genome Sequencing and Medical Records to Inform Clinical Practice,” published in the October 2024 issue of Oncology by Leong et al.
The 100,000 Genomes Project aims to analyze genetic variants associated with drug-induced toxicity in patients with cancer.
Researchers conducted a retrospective study utilizing whole-genome sequencing (WGS) to assess variants of pharmacogenomic (PGx) related to drug toxicity in patients with cancer.
They analyzed germline WGS data from 76,805 participants for variants of PGx in 4 genes (DPYD, NUDT15, TPMT, UGT1A1) linked to toxicity from 5 cancer drugs (capecitabine, fluorouracil, mercaptopurine, thioguanine, irinotecan). A phenome-wide association study (PheWAS) was conducted to correlate genomic data with prescribing and hospital incidence records to identify adverse drug reactions (ADRs). In a subset of 7,081 patients with cancer, variants of DPYD were communicated to clinicians, and patient outcomes were subsequently collected.
The results showed that clinically relevant variants of PGx were identified in 62.7% of participants, indicating that approximately 14,540 patients annually could benefit from reduced doses or alternative therapies to minimize the risk of ADRs. Furthermore, significant associations were observed between variants of PGx in DPYD and toxicity-related phenotypes in patients treated with capecitabine or fluorouracil, with reported variants of DPYD found to be informative for clinical decision-making in most cases.
They concluded that reporting variants of PGx from germline, WGS can inform prescribing decisions and reduce the risk of ADRs in patients with cancer.
Source: ascopubs.org/doi/10.1200/JCO.23.02761
