Gene score predicts prostate cancer risk
A polygenic hazard score appears to accurately estimate genetic risk and predict age at onset of aggressive prostate cancer, a recent study shows.
Using single nucleotide polymorphisms of 31,747 males, the researchers developed a polygenic hazard score to assess individual prostate cancer genetic risk and applied it to a cohort of 6,411 males. The main outcome was the predictive accuracy for age of onset of aggressive malignancy in the validation cohort.
According to a Cox proportional hazards model, the polygenic hazard score showed significant predictive ability for the age of onset of aggressive prostate cancer (z=11.2; p<10-16), any prostate cancer (z=15.4; p<10-16) and very aggressive prostate cancer (z=6.8; p<10-11).
Those in the >98th percentile of polygenic hazard scores were identified as high-risk patients and showed significantly higher risks of any prostate cancer (hazard ratio [HR], 2.5; 95 percent CI, 2.2–2.8), aggressive disease (HR, 3.0; 2.2–4.0) and early age of onset (HR, 2.9; 2.4–3.4).
A model developed using only aggressive prostate cancer cases also showed significant predictive value but did not outperform the original model (z=9.4; p<10-16; HR, 2.6; 2.1–3.1).
In a subsequent Cox test performed on patients with known family history statuses, there was no correlation between age of onset of aggressive disease and family history (z=0.9; p=0.37; HR, 1.1; 0.9–1.4).
Inclusion of family history in the model did not improve the predictive value over the original polygenic hazard score for any prostate cancer (p=0.14) or aggressive prostate cancer (p=0.59).