Polygenic risk scores to stratify cancer screening should predict mortality not incidence Review
| Authors: | Vickers, A. J.; Sud, A.; Bernstein, J.; Houlston, R. |
| Review Title: | Polygenic risk scores to stratify cancer screening should predict mortality not incidence |
| Abstract: | Population-based cancer screening programs such as mammography or colonscopy generally directed at all healthy individuals in a given age stratum. It has recently been proposed that cancer screening could be restricted to a high-risk subgroup based on polygenic risk scores (PRSs) using panels of single-nucleotide polymorphisms (SNPs). These PRSs were, however, generated to predict cancer incidence rather than cancer mortality and will not necessarily address overdiagnosis, a major problem associated with cancer screening programs. We develop a simple net-benefit framework for evaluating screening approaches that incorporates overdiagnosis. We use this methodology to demonstrate that if a PRS does not differentially discriminate between incident and lethal cancer, restricting screening to a subgroup with high scores will only improve screening outcomes in a small number of scenarios. In contrast, restricting screening to a subgroup defined as high-risk based on a marker that is more strongly predictive of mortality than incidence will often afford greater net benefit than screening all eligible individuals. If PRS-based cancer screening is to be effective, research needs to focus on identifying PRSs associated with cancer mortality, an unchartered and clinically-relevant area of research, with a much higher potential to improve screening outcomes. |
| Keywords: | lung-cancer; overdiagnosis |
| Journal Title: | npj Precision Oncology |
| Volume: | 6 |
| ISSN: | 2397-768X |
| Publisher: | Springer Nature |
| Date Published: | 2022-05-30 |
| Start Page: | 32 |
| Language: | English |
| ACCESSION: | WOS:000803304000001 |
| DOI: | 10.1038/s41698-022-00280-w |
| PROVIDER: | wos |
| PMCID: | PMC9151796 |
| PUBMED: | 35637246 |
| Notes: | Review -- 32 -- Source: Wos |
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