Association of Genetic Risk for Prostate Cancer With Early Prostate Cancer Death

In a study reported in JAMA Network Open, Plym et al found that men at a higher genetic risk for prostate cancer were more likely to experience early death from prostate cancer compared to men with a lower genetic risk for the disease.

Study Details

The cohort study used a combined analysis of genotyped men without prostate cancer at inclusion and with lifestyle data in two prospective cohort studies—the Malmö Diet and Cancer Study (MDCS; n = 10,270) in Sweden and the Health Professionals Follow-Up Study (HPFS; n = 9,937) in the United States—with follow-up taking place from 1991 to 2019. Men were categorized according to modifiable lifestyle behaviors and genetic risk. Polygenic risk score above the median or a family history of cancer defined men as at higher genetic risk; the remaining men were categorized as at lower genetic risk.

Key Findings

Of the total of 19,607 men included in the analysis, 13,186 (67%)—including 72% in the MDCS cohort and 62% in the HPFS cohort—were classified as having higher genetic risk. The median patient age at the start of follow-up was 59.0 years in the MDCS cohort and 65.1 years in the HPFS cohort.

During follow-up, 107 early prostate cancer deaths (ie, by age 75 years) and 337 late prostate cancer deaths (ie, at ≥ age 75 years) were observed. Compared with men at lower genetic risk, those at higher genetic risk had an increased risk for both early (hazard ratio [HR] = 3.26, 95% confidence interval [CI] = 1.82–5.84) and late (HR = 2.26, 95% CI = 1.70–3.01) prostate cancer death. Higher lifetime incidence of prostate cancer death was observed among men with higher vs lower genetic risk in both the MDCS cohort (3.1% vs 1.3%) and the HPFS cohort (2.3% vs 0.6%).

Men at higher genetic risk accounted for 94 (88%) of 107 early prostate cancer deaths (88%). Of these, 36% were estimated to be preventable through adherence to healthy lifestyle elements, such as not smoking, healthy weight, high physical activity, and healthy diet.

The investigators concluded, “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. This suggests that men at increased genetic risk should be targeted in prostate cancer prevention strategies.”

Anna Plym, PhD, of the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, is the corresponding author for the JAMA Network Open article.

Disclosure: The study was supported by the National Cancer Institute, Prostate Cancer Foundation, American Cancer Society, Swedish Cancer Society, and others. For full disclosures of the study authors, visit jamanetwork.com.