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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.

SUBMITTER: Vickers AJ

PROVIDER: S-EPMC9151796 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Polygenic risk scores to stratify cancer screening should predict mortality not incidence.

Vickers Andrew J AJ Sud Amit A Bernstein Jonine J Houlston Richard R

NPJ precision oncology 20220530 1

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 associ ...[more]

PMID: 35637246

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Polygenic risk scores to stratify cancer screening should predict mortality not incidence.

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Polygenic risk scores to stratify cancer screening should predict mortality not incidence.

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