Targeting lung cancer screening to individuals at greatest risk: the role of genetic factors

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Lung cancer (LC) is the most common global cancer. An individual’s risk of developing LC is mediated by an array of factors, including family history of the disease. Considerable research into genetic risk factors for LC has taken place in recent years, with both low and high-penetrance variants implicated in increasing or decreasing a person’s risk of the disease. LC is the leading cause of cancer death worldwide; poor survival is driven by late onset of non-specific symptoms, resulting in late-stage diagnoses. Evidence for the efficacy of screening in detecting cancer earlier, thereby reducing lung-cancer specific mortality, is now well established. To ensure the cost-effectiveness of a screening programme, and to limit the potential harms to participants, a risk threshold for screening eligibility is required. Risk prediction models (RPM), which provide an individual’s personal risk of LC over a particular period based on a large number of risk factors, may improve the selection of high-risk individuals for LC screening when compared with generalised eligibility criteria which only consider smoking history and age. No currently used RPM integrates genetic risk factors into its calculation of risk. This review provides an overview of the evidence for LC screening, screening related harms and the use of RPMs in screening cohort selection. It gives a synopsis of the known genetic risk factors for lung cancer, and discusses the evidence for including them in RPMs, focussing in particular on the use of polygenic risk scores to increase the accuracy of targeted lung cancer screening.

Bibliographical metadata

Original languageEnglish
Article number107399
JournalJournal of Medical Genetics
Early online date29 Jan 2021
Publication statusPublished - 29 Jan 2021