In a study reported in the Journal of Clinical Oncology, Nyberg et al developed the risk model CanRisk-Prostate for predicting the development of prostate cancer based on age, detailed cancer family history, moderate- to high-risk pathogenic variants, and a polygenic score for common low-risk variants.
Study Details
The model was developed using data from a kin-cohort including individuals from 16,633 prostate cancer families identified in the United Kingdom (UK) between 1993 and 2017 from the UK Genetic Prostate Cancer Study. The model was validated in an independent prospective cohort of 170,850 unaffected patients enrolled in the UK Biobank prospective cohort study between 2006 and 2010; among these, there were 3,456 incident prostate cancer cases within 5 years and 7,624 within 10 years.
Key Findings
The model consisted of age; detailed cancer family history; moderate- to high-risk BRCA2, HOXB13, and BRCA1 pathogenic variants; and a polygenic score for 268 common low-risk single-nucleotide polymorphism variants.
In the validation cohort, the model discriminated between unaffected patients and patients with incident prostate cancer with C-index values of 0.790 (95% confidence interval [CI] = 0.783–0.797) for cancer developing within 5 years and 0.772 (95% CI = 0.768–0.777) for cancer developing within 10 years.
In the validation cohort, patients with the top 1% of predicted risks accounted for 7.2% and 5.8% of incident cancer cases at 5 and 10 years, respectively. Those in the top 10% accounted for 38.5% and 34.8% of cases; those in the top 50% accounted for 89.1% and 86.3% of cases.
The investigators concluded, “To our knowledge, this is the first validated risk model offering personalized prostate cancer risks. The model will assist in counseling [patients] concerned about their risk and can facilitate future risk-stratified population screening approaches.”
Tommy Nyberg, PhD, of the Centre for Cancer Genetic Epidemiology, University of Cambridge, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Cancer Research UK, Prostate Cancer UK, and others. For full disclosures of the study authors, visit ascopubs.org.
