Connection Between Genetic Risk, Early Death Among Patients With Prostate Cancer

A study from Anna Plym, PhD, and colleagues published in JAMA Network Open investigated the association between high versus low genetic risk and early death in patients with prostate cancer.

Researchers evaluated the data from 2 cohort studies, including from genotyped men without prostate cancer and with lifestyle data. Patients were sorted into groups based on modifiable lifestyle behaviors and genetic risk.

Those with a polygenic risk score higher than the median or a family history of cancer (67%) were determined to have a higher genetic risk. The other participants were reported to have a lower genetic risk.

Primary end points for the research included time-to-event analysis estimating hazard ratios (HR), absolute risks, and preventable deaths by age.

Of the 19,607 patients, investigators noted 107 early deaths and 337 deaths attributable to prostate cancer. They reported that patients at a higher genetic risk of prostate cancer experienced higher rates of early (HR, 3.26; 95% CI, 1.82-5.84) and late (HR, 2.26; 95% CI, 1.70-3.01) prostate cancer death compared with those who had a lower genetic risk. Patients with a higher genetic risk also faced an increased lifetime risk of prostate cancer death.

Ninety-four (88%) of the 107 early prostate cancer-related deaths were attributed to patients with an increased genetic risk. Of those early deaths, researchers noted that 36% (95% CI, 12-60) were preventable following adherence to healthy lifestyle behaviors, including not smoking, a healthy weight, high physical activity, and a healthy diet.

“In this 20-year follow-up study, men with a genetic predisposition accounted for the vast majority of early prostate cancer deaths, of which one-third were estimated to be preventable,” the researchers wrote. “This [finding] suggests that men at increased genetic risk should be targeted in prostate cancer prevention strategies.”