A new genetic tool, the polygenic hazard score, was a “highly significant predictor” of age of onset of aggressive prostate cancer was recently described in BMJ.
“The good news is we have excellent, curative treatment options (surgery or radiation therapy) when the disease is detected in its early stages,” Tyler Seibert, MD, PhD, of the Center for Multimodal Imaging & Genetics at the University of California at San Diego, told Healio Family Medicine. “However, prostate cancer screening of the whole population has been problematic because of many false positives and overly aggressive treatment of slow-growing forms of the disease.”
Researchers added that prior studies used genome-wide associations polymorphisms to foretell risk for aggressive prostate cancer. “Epidemiological data, however, show that risk of [aggressive prostate cancer] is not a simple dichotomy of cases and controls but rather is highly dependent on increasing age,” they wrote.
Seibert and colleagues analyzed aggressive prostate cancer status, genotypes, and age to choose single nucleotide polymorphisms (SNPs) linked to diagnosis. The SNPs then were analyzed to estimate their effects on age at diagnosis of aggressive prostate cancer based on a Gleason score of 7 or greater, PSA concentration of 10 ng/L or greater, having stage T3 to T4, and both nodal and distant metastasis.
The dataset included 31,747 men; the validation dataset comprised 6,411 men.
Seibert and colleagues found that in the independent validation set, the hazard score calculated from 54 SNPs was a highly significant predictor of age at diagnosis of aggressive cancer (z = 11.2; P < 10–16). The HR for aggressive cancer was 2.9 (95% CI, 2.4–3.4) when scores in the 98th percentile or greater were compared with those with scores in the 30th to 70th percentile. In addition, polygenic hazard score performance remained high when family history was accounted for, but including family history in a combined model did not improve prediction of onset of aggressive prostate cancer (P = .59), Also, the positive predictive value of PSA screening for aggressive prostate cancer increased with increasing polygenic hazard score.
“Currently, primary care doctors are expected to make a recommendation for each patient regarding screening — both whether to screen and at what age to start — but they are not given a lot of reliable, objective information to help inform that decision. The polygenic hazard score could help the primary care doctor provide a personalized decision for each patient based on that individual's own DNA,” Seibert said in the interview. “This study shows the tremendous potential of genetic scores to predict which men are at risk of developing aggressive prostate cancer at a young age.”
He said replicating the findings is one of several next steps for researchers.
“The next big question for us is how this applies to men of non-European genetic ancestry. The tool was developed and validated in a large genetic database that came from studies in men of European ancestry, so it is critically important to us to now make sure we have a useful tool for men of all genetic backgrounds,” Seibert said.
He added it would be reasonable to assume the polygenic hazard score could be available in clinical practice within a few years. – by Janel Miller
Disclosure: Seibert reports no relevant disclosures. Please see the study for a full list of the other authors relevant financial disclosures.