The following is a summary of “Family History of Prostate and Breast Cancer Integrated with a Polygenic Risk Score Identifies Men at Highest Risk of Dying from Prostate Cancer before Age 75 Years” published in the November 2022 issue of Clinical Cancer by Plym et al.

One of the few widely acknowledged risk factors for prostate cancer is a family history of the disease. It is unclear how much additional value may be added to lifetime risk classification for prostate cancer by evaluating inherited polygenic risk factors beyond those revealed by family history. Risk of prostate cancer and death from prostate cancer were evaluated by following 10,120 men in the Health Professionals Follow-up Study and using their existing genetic data. Researchers evaluated the ability of a validated polygenic risk score (PRS) incorporating 269 prostate cancer risk variants to identify males at risk for prostate cancer and prostate cancer death throughout the age span, in addition to a personal or family history of prostate or breast cancer.

A total of 1,915 cases of prostate cancer and 166 deaths from the disease were recorded throughout a 20-year observation period. The highest rates of prostate cancer and prostate cancer-specific death were observed among men in the highest PRS quartile who also had a family history of prostate or breast cancer. The prostate cancer hazard ratio (HR) was 6.95 [95% CI, 5.57-8.66] and the prostate cancer mortality hazard ratio (HR) was 4.84 [95% CI, 2.59-9.03] in comparison to the lowest genetic risk group of men (lowest PRS quartile and no family history). 

By age 75, 97.5% of prostate cancer deaths occurred in men in the 2 highest PRS quartiles (50–100%) or in men with a family history of prostate or breast cancer (61.8%). Our results suggest that males who are at the highest risk of dying from prostate cancer before the age of 75 can be identified using risk stratification based on family history and inherited polygenic risk.