Discovering novel germline genetic variants linked to severe fluoropyrimidine-related toxicity in- and outside DPYD.
Jonathan E KnikmanQinglian ZhaiCarin A T C LunenburgLinda M HenricksStefan BöhringerMaaike van der LeeFemke M de ManSteven M OfferShikshya ShresthaGeert-Jan CreemersArnold BaarsVincent O DezentjéAlexander L T ImholzFrank J F JeurissenJohanna E A PortieljeRob L H JansenPaul HambergHelga J DroogendijkMiriam KoopmanPeter NieboerMarlène H W van de PoelCaroline M P W MandigersRon H N van SchaikHans GelderblomRon H J MathijssenJan H M SchellensAnnemieke CatsHenk-Jan GuchelaarJesse J SwenPublished in: Genome medicine (2024)
Results from DPYD exon sequencing and GWAS analysis did not identify additional genetic variants associated with severe toxicity, which suggests that testing for single markers at a population level currently has limited clinical value. Identifying additional variants on an individual level is still promising to explain fluoropyrimidine-related severe toxicity. In addition, studies with larger samples sizes, in more diverse cohorts are needed to identify potential clinically relevant genetic variants related to severe fluoropyrimidine toxicity.