Individualized polygenic hazard scores may help predict the age of onset of prostate cancer (PCa) aggression, according to a study published in the BMJ.
Tyler M Seibert, MD, of the Center for Multimodal Imaging and Genetics at the University of California in San Diego, and associates conducted tests to analyze prostate cancer severity, age at single nucleotide polymorphisms affiliated with cancer diagnosis, and genotype to generate a “genetic tool” to assist in the prediction of aggressive prostate cancer age, who should be screened for PCa, and at what age.
The study consisted of 31,747 men of European decent with provided age, PCa status, and genotypic data. Of the participants, 18,868 had PCa, 10,635 had aggressive PCa, 5406 had very aggressive PCa, and 12,879 were controls. There were 201,043 single nucleotide polymorphisms provided for the analysis, 2415 of which were linked to an elevated risk for PCa. Due to incomplete data sets, 4803 patients (and 43 polymorphisms) were excluded from the investigation.
In an independent validation dataset, consisting of 6411 men, a statistically significant hazard score (yielded from 54 single nucleotide polymorphisms) predicted diagnosis age for aggressive cancer (z=11.2).
High scores (men > 98th centile) were compared with average scores (men 30th to 70th centile). The obtained hazard ratio was 2.9 for aggressive cancer. The addition of family history did not improve prediction rates (HR, 1.1).
Compared with average risk, high scoring men had a hazard ratio of 2.9. In addition, the score also helped predict any PCa, as well as very aggressive PCa (z=15.4 and z=6.8, respectively).
“This study presents and validates a novel polygenic hazard score that is an indicator of age of onset of aggressive PCa,” the authors noted.
“This genetic risk model might play a role in guiding decisions about whether and when to screen for PCa,” they continued. “Investigation into the relation between the score and early midlife [prostate specific antigen] testing is warranted.”
- Seibert TM, Fan CC, Wang Y, et al. Polygenic hazard scored to guide screening for aggressive prostate cancer: development and validation in large scale cohorts. BMJ. 2018 Jan 10. doi: 10.1136/bmj.5757