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Genetic risk model could guide prostate cancer screening

Polygenic hazard score could help guide whom and when to screen for prostate cancer

Louise Prime

Thursday, 11 January 2018

A polygenic hazard score can be used for personalised genetic risk estimates that can predict for age at onset of aggressive prostate cancer (PCa), researchers have reported* in today’s BMJ. As the scoring assessment is relatively inexpensive and can predict the utility of PSA testing for an individual man, they suggested that their new score could help to objectively guide decisions on whom to screen and when.

Worldwide, prostate cancer is newly diagnosed in more than a million men every year, and was associated with an estimated 300,000 deaths in 2012. Prostate specific antigen (PSA) screening has the potential to detect prostate cancer early, potentially allowing time for treatment to save a man’s life. But universal screening is widely rejected by many guidelines because of both the high rate of false positives (elevated PSA levels in men without prostate cancer); and the risk of overtreatment (many men with prostate cancer never develop aggressive disease).

A large international team of researchers analysed more than 200,000 single nucleotide polymorphisms (SNPs) from 31,747 men of European ancestry from the international PRACTICAL consortium, to develop a polygenic hazard score (PHS) –an assessment of individual genetic risk of developing aggressive PCa. Then they applied the final model to an independent dataset containing genotype and PSA screening data for 6,411 men in an independent clinical trial, and calculated the hazard score for these men to test prediction of survival free from PCa.

The study authors reported that, in the independent validation, the hazard score was a highly significant predictor of age at diagnosis of aggressive PCa. In this validation set, men with high scores (>98th centile) had almost three times the risk (hazard ratio 2.9) of aggressive cancer compared with men with average scores (30th-70th centile). Inclusion of family history in a combined model did not improve prediction of onset of aggressive PCa, and PHS performance remained high when family history was accounted for. Furthermore, they said, the positive predictive value of PSA screening for aggressive PCa was increased with increasing PHS.

They concluded that their new polygenic hazard score for personalised genetic assessment of individual age-associated risk of PCa, validated in an independent dataset, shows “accurate prediction of onset of aggressive PCa”. They added: “Moreover, the score can predict the utility of PSA testing for an individual man. This genetic risk model might play a role in guiding decisions about whether and when to screen for PCa. Investigation into the relation between the score and early midlife PSA testing is warranted.”

They also commented: “The score is a relatively inexpensive assessment of an individual man’s age-specific risk and provides objective information on whether a given patient might benefit from PSA screening.”


*Seibert TM, Chun Chieh F, Yunpeng W, et al. Polygenic hazard score to guide screening for aggressive prostate cancer: development and validation in large scale cohorts. BMJ 2018; 360: j5757. doi: 10.1136/bmj.j5757

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