Prevalence of Adverse Germline Genetic Variants in Prostate Cancer


Key Points

  • Deleterious germline variants were identified in 17.2% of patients.
  • Many men with positive variants would not have been eligible for genetic testing on current guidelines.

In a study reported in JAMA Oncology by Nicolosi et al, it was found that 17% of men with prostate cancer had likely deleterious germline genetic variants, and that many of these men would not have been considered candidates for genetic testing.

Study Details

The study involved data from 3,607 men with history of prostate cancer who underwent germline genetic testing between 2013 and 2018 and were unselected for family history, stage of disease, or age at diagnosis. Referral-based testing was performed at a Clinical Laboratory Improvement Amendments/College of American Pathologists–certified diagnostic laboratory. Analyses were performed between February 2017 and August 2018.

Prevalence of Positive Variants

Among the 3,607 men, 620 (17.2%) had positive (ie, pathogenic, likely pathogenic, and increased risk) germline variants. The 10 most common variants were BRCA2 (24.3%), CHEK2 (14.1%), ATM (9.6%), MUTYH (8.2%), BRCA1 (6.4%), HOXB13 (4.5%), APC (4.5%), MSH2 (3.4%), TP53 (3.3%), and PMS2 (2.7%). In total, BRCA1/2 variants accounted for 30.7% of variants. DNA mismatch repair variants (PMS2, MLH1, MSH2, MSH6) with known therapeutic implications accounted for 1.74% of the variants in the total population tested. Positive germline variants were found in 15.1% of patients with Gleason scores ≤ 6 and in 16.3% of patients with Gleason scores ≥ 7.

Among the 674 positive variants identified, 291 (43.8%) were in genes indicated for testing in the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for prostate cancer (version 3.2018) (BRCA1/2, ATM, PALB2, and FANCA). Evaluation of self-reported family histories showed that 229 men (37%) with positive variants in the cohort would not have been considered eligible for genetic testing using the NCCN Guidelines for genetic/familial breast and ovarian for patients with prostate cancer.

The investigators concluded: “Current NCCN Guidelines and Gleason scores cannot reliably stratify patients with prostate cancer for the presence or absence of pathogenic germline variants. Most positive genetic test results identified in this study have important management implications for patients and their families, which underscores the need to revisit current guidelines.”

Oliver Sartor, MD, Tulane Cancer Center, Tulane Medical School, is the corresponding author for the JAMA Oncology article.

Disclosures: The study authors' full disclosures can be found at

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.