M. Eileen Dolan
The University of Chicago, USA
Title: Role of Pharmacogenomics in identifying cancer survivors at risk for adverse, persistent toxicities
Biography
Biography: M. Eileen Dolan
Abstract
Statement of the Problem: There are now over 28 million cancer survivors worldwide, and as a result, there is a heightened awareness of the long-term toxicities resulting from treatment and their impact on quality of life. Understanding the role of germline genetic factors in the development of cancer treatment-related toxicities is critical for the identification of patients at risk as well as for the development of drugs to treat or prevent these toxicities. The purpose of this presentation is to review current understanding of genetic susceptibility to adverse outcomes among cancer survivors following chemotherapy with a particular focus on genome-wide association studies (GWAS). Few of the findings from earlier narrowly focused candidate gene studies have been replicated in independent populations. A major strength of genome-wide approaches is that they do not require assumptions about the genes or pathways involved in the pharmacologic trait. The challenges include the need for large cohorts of patients with homogeneous treatment exposures and systematic evaluation of well-defined outcomes as well as replication in independent study populations. Persistent calls to incorporate ancestrally diverse populations into genomic efforts resulted in a recent rise in the number of studies utilizing cohorts of East Asian descent; however, few pharmacogenomic studies to date include cohorts of African, Native American and admixed populations. These disparities could contribute to the widening gaps in health outcomes. In addition to discussing an overview of this approach, the presentation will pay particular attention to recent studies identifying genetic variants associated with chemotherapy-induced peripheral neuropathy and ototoxicity (hearing loss and tinnitus). Conclusion & Significance: Genetic associations hold tremendous promise for more precisely identifying patients at highest risk for developing adverse treatment effects and potential identification of targets for prevention or treatment of the long-term toxicities associated with chemotherapy.