Project 466643

Fluoropyrimidines are commonly prescribed anti-cancer drugs but they cause severe adverse drug reactions in up to a third of patients. The same dose of one drug may be efficacious and safe in one person but cause a severe adverse drug reaction in another. Genetic variation is a key factor that influences the occurrence of serious adverse drug reactions. In the case of fluoropyrimidines, 3-8% of the western population has genetic variation in the gene DPYD that puts them at over 70% risk for severe fluoropyrimidine adverse drug reactions. These people can often be safely treated with lower fluoropyrimidine doses. The goal of the Canadian Pharmacogenomics Network for Drug Safety (CPNDS) is to implement testing of genetic markers to predict the risk of adverse drug reactions. Therefore, I aim to use the resources of CPNDS to implementDPYD genetic testing at BC Cancer Agency, where people who test positive receive a reduced dose of fluoropyrimidines to prevent severe adverse drug reactions. This is highly relevant for a patients quality of life because adverse drug reactions result in hospitalizations and discontinuation of anti-cancer treatments. I will evaluate theDPYDtesting program by analyzing the extent fluoropyrimidine adverse drug reactions and related care are reduced after the program.Additionally, I aim to develop an analytical plan for identifying novel genetic variants associated with fluoropyrimidine adverse drug reactions with the genetic material collected in this study. Using genetics to reduce the risk of adverse drug reactions and inform treatment decisions is an essential part of precision medicine and will improve health outcomes for Canadians, as well as the 2 million patients per year all around the world who use fluoropyrimidines.