Polygenic risk scores: the future of cancer risk prediction, screening, and precision prevention

Abstract

Genome-wide association studies (GWASs) have shown that the genetic architecture of cancers are highly polygenic and enabled researchers to identify genetic risk loci for cancers. The genetic variants associated with a cancer can be combined into a polygenic risk score (PRS), which captures part of an individual’s genetic susceptibility to cancer. Recently, PRSs have been widely used in cancer risk prediction and are shown to be capable of identifying groups of individuals who could benefit from the knowledge of their probabilistic susceptibility to cancer, which leads to an increased interest in understanding the potential utility of PRSs that might further refine the assessment and management of cancer risk. In this context, we provide an overview of the major discoveries from cancer GWASs. We then review the methodologies used for PRS construction, and describe steps for the development and evaluation of risk prediction models that include PRS and/or conventional risk factors. Potential utility of PRSs in cancer risk prediction, screening, and precision prevention are illustrated. Challenges and practical considerations relevant to the implementation of PRSs in health care settings are discussed.

Keywords

• cancer screening
• genome-wide association study (gwas)
• polygenic risk score (prs)
• precision prevention
• risk prediction model