Potential Utility of Polygenic Risk Scores in Cancer Screening in the United Kingdom

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In a modeling study reported in The Lancet Oncology, Huntley et al found that the extension of UK cancer screening programs for breast, prostate, and colorectal cancers to a polygenic risk score (PRS)-defined high-risk group of patients with cancer may improve cancer case detection and avoidance of death.

Study Details

The study used data on age-stratified cancer incidence for the UK population from the National Cancer Registration Dataset for 2016 to 2018. Percentage of cases of cancer captured and number of deaths averted were calculated according to screening using five PRS-defined high-risk quantiles: top 50%, 20%, 10%, 5%, and 1%.

Key Findings

The PRS-defined high-risk quintile (20%) of the population was estimated to capture 37% of breast cancer cases, 46% of prostate cancer cases, 34% of colorectal cancer cases, 29% of pancreatic cancer cases, 26% of ovarian cancer cases, 22% of renal cancer cases, 26% of lung cancer cases, and 47% of testicular cancer cases.

Extending UK screening programs to a PRS-defined high-risk quintile including persons aged 40 to 49 years for breast cancer, 50 to 59 years for colorectal cancer, and 60 to 69 years for prostate cancer could avert a maximum of 102, 188, and 158 deaths annually, respectively. In contrast, non–PRS-stratified screening in the full population of persons aged 48 to 49 years for breast cancer, 58 to 59 years for colorectal cancer, and 68 to 69 years for prostate cancer would use equivalent resources and potentially avert a maximum of 80, 155, and 95 deaths annually, respectively.

As noted by the investigators, “These maximal modeled numbers will be substantially attenuated by incomplete population uptake of PRS profiling and cancer screening, interval cancers, non-European ancestry, and other factors.”

The investigators concluded, “Under favorable assumptions, our modeling suggests modest potential efficiency gain in cancer case detection and deaths averted for hypothetical new PRS-stratified screening programs for breast, prostate, and colorectal cancer[s]. Restriction of screening to high-risk quantiles means many or most incident cancers will arise in those assigned as being [at] low risk. To quantify real-world clinical impact, costs, and harms, UK-specific cluster-randomized trials are required.”

Clare Turnbull, PhD, of the Division of Genetics and Epidemiology, The Institute of Cancer Research, London, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by The Wellcome Trust. For full disclosures of the study authors, visit

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