Polygenic Hazard Score Predicts Age of Prostate Cancer Diagnosis

(HealthDay News) — A hazard score calculated from 54 single nucleotide polymorphisms can predict age at diagnosis of aggressive prostate cancer (PCa), according to a study published online in The BMJ.

Tyler M. Seibert, MD, from the University of California, San Diego, in La Jolla, and colleagues developed and validated a genetic tool to predict age of onset of aggressive PCa. Single nucleotide polymorphisms associated with diagnosis were selected in analysis of genotype, PCa status, and age. To estimate their effects on age at diagnosis of aggressive PCa, these polymorphisms were incorporated into a survival analysis. The development and validation datasets comprised 31,747 and 6411 men, respectively.

The researchers found that the hazard score calculated from 54 single nucleotide polymorphisms significantly predicted age at diagnosis of aggressive cancer in the independent validation set. The hazard ratio for aggressive cancer was 2.9 when comparing men in the validation set with high scores (>98th centile) to those with average scores (30 to 70th centile). Prediction of onset of aggressive PCa was not improved by inclusion of family history in a combined model; when family history was accounted for, polygenic hazard score performance remained high. With increasing polygenic hazard score, the positive predictive value of prostate-specific antigen screening for aggressive PCa was increased.

“Polygenic hazard scores can be used for personalized genetic risk estimates that can predict for age at onset of aggressive PCa,” the authors write.

Several authors disclosed financial ties to the pharmaceutical and medical technology industries.

Reference

Seibert TM, Fan CC, Wang Y, 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