Applying a genetic risk score for prostate cancer to men with lower urinary tract symptoms in primary care to predict prostate cancer diagnosis: a cohort study in the UK Biobank

Abstract

Background Prostate cancer is highly heritable, with >250 common variants associated in genome-wide association studies. It commonly presents with non-specific lower urinary tract symptoms that are frequently associated with benign conditions. Methods Cohort study using UK Biobank data linked to primary care records. Participants were men with a record showing a general practice consultation for a lower urinary tract symptom. The outcome measure was prostate cancer diagnosis within 2 years of consultation. The predictor was a genetic risk score of 269 genetic variants for prostate cancer. Results A genetic risk score (GRS) is associated with prostate cancer in symptomatic men (OR per SD increase = 2.12 [1.86–2.41] P = 3.5e-30). An integrated risk model including age and GRS applied to symptomatic men predicted prostate cancer (AUC 0.768 [0.739–0.796]). Prostate cancer incidence was 8.1% (6.7–9.7) in the highest risk quintile. In the lowest quintile, prostate cancer incidence was <1%. Conclusions This study is the first to apply GRS in primary care to improve the triage of symptomatic patients. Men with the lowest genetic risk of developing prostate cancer could safely avoid invasive investigation, whilst those identified with the greatest risk could be fast-tracked for further investigation. These results show that a GRS has potential application to improve the diagnostic pathway of symptomatic patients in primary care.

Determining the role of genetic risk scores in symptomatic cancer detection

“…A recent study showed that a prostate cancer GRS could improve risk stratification in primary care. 8 …”

Does polygenic risk for substance‐related traits predict ages of onset and progression of symptoms?

“…A recent large study of white European‐ancestry (EUR) individuals in the UK Biobank showed the utility of a prostate cancer genetic risk score for triaging patients in primary care. Men in the highest quintile of risk had a prostate cancer incidence of 8.1% and could be fast‐tracked for further investigation, while the incidence among those in the lowest risk quintile was < 1% and they could more safely avoid invasive investigation [16]. Thus, there currently are clinical applications of PRS to differentiate individuals based on their genetic risk for a disease.…”

Adverse Childhood Events, Mood and Anxiety Disorders, and Substance Dependence: Gene X Environment Effects and Moderated Mediation

“…Polygenic risk scores (PRS), calculated by summing the effects of genetic variants across the genome, can reflect an individual's aggregate genetic liability for a particular trait or disorder. The effects of PRS, if large enough, could be useful clinically 33,34,35 . We therefore also examined PRS for M/ADs and SD as moderators of the direct and indirect effects of ACEs in both models.…”