In a study reported in the Journal of Clinical Oncology, Jennifer L. Beebe-Dimmer, MPH, PhD, and colleagues found that risk of prostate cancer varied according to cancer family history, with the strongest association being observed between family history and early-onset prostate cancer.

Jennifer L. Beebe-Dimmer, MPH, PhD

Study Details

In the study, 619,630 men age ≥ 40 who were members of a pedigree that included at least three consecutive generations were identified from the Utah Population Database. Each was individually assessed for history of familial prostate cancer, hereditary prostate cancer (using more stringent definition vs familial prostate cancer), hereditary breast and ovarian cancer, Lynch syndrome, and personal prostate cancer status.

Cases of prostate cancer were classified into the subtypes of early-onset, lethal, and clinically significant. Analyses adjusted for covariables were used to determine relative risks for each subtype and for each family history category.

Key Findings

Overall, 36,360 men (5.9% of cohort) had prostate cancer, with 2,562 (7.0%) having early-onset disease, 4,044 (11.1%) having lethal disease, and 15,201 (41.8%) having clinically significant disease.

Family history of hereditary prostate cancer was associated with the highest risk for all prostate cancer subtypes combined (relative risk [RR] = 2.30, 95% confidence interval [CI] = 2.22–2.40), followed by familial prostate cancer (RR= 1.81, 95% CI = 1.76–1.86), hereditary breast and ovarian cancer (RR = 1.47, 95% CI = 1.43–1.50), and Lynch syndrome (RR = 1.16, 95% CI = 1.12–1.19).

Overall, the greatest risk associated with any family history category was for early-onset disease. For example, hereditary prostate cancer was associated with relative risks of 3.93 (95% CI = 3.33–4.61) for early-onset disease, 2.21 (95% CI = 1.95–2.50) for lethal disease, and 2.32 (95% CI = 2.17–2.48) for clinically significant disease. Familial prostate cancer was associated with relative risks of 3.38 for early-onset disease, 1.70 for lethal disease, and 1.79 for clinically significant disease (all statistically significant).

Hereditary breast and ovarian cancer was associated with relative risks of 2.05 for early-onset disease, 1.39 for lethal disease, and 1.47 for clinically significant disease (all statistically significant). Lynch syndrome was associated with relative risks of 1.34 for early-onset disease, 1.08 for lethal disease, and 1.15 for clinically significant disease (all but association with lethal disease statistically significant).

The investigators concluded: “In this large, population-based, family database, the risk of [prostate cancer] varied by cancer [family history] and was most strongly associated with [early-onset] disease. These results are critically valuable in understanding and targeting high-risk populations that would benefit from genetic screening and enhanced surveillance.”

Kathleen A. Cooney, MD, of Duke University School of Medicine, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by the Huntsman Cancer Foundation, National Institutes of Health, National Cancer Institute, and others. For full disclosures of the study authors, visit ascopubs.org.