Using Big Data to Uncover Drug-Gene Interaction in Patients with Prostate Cancer

Pharmacogenomics (PGx) enables personalized medication optimization, potentially improving clinical outcomes, particularly for older adults who frequently experience polypharmacy. CYP2D6 is an enzyme that plays a crucial role in the metabolism of many drugs. The prevalence of CYP2D6 variants and their impact on potential drug-gene interactions in patients with prostate cancer (PPC), who are mostly represented by older adults, have not been systematically investigated. In this study, we analyzed the genotypes and phenotypes for CYP2D6 gene and medical prescription of over 3000 PPC enrolled in the All of Us research program. We found that about 20% of the patients were identified as non-normal metabolizer types with increased or reduced function. 67% of the patients had at least one medication mainly or partly metabolized by CYP2D6. 13% of the patients had an actionable phenotype and prior exposure to an impacted medication. These findings suggest a potential roadmap for improvement of medication prescription in PPC using PGx guidelines in routine clinical practice.