# Prevalence of germline variants in prostate cancer and implications for current genetic testing guidelines

Source: https://onco.cc/key-papers/paper-nicolosi-germline-variants-prostate-testing-guidelines-jama-oncol-2019/  
OnCo record `paper-nicolosi-germline-variants-prostate-testing-guidelines-jama-oncol-2019` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Testing 3,607 men with prostate cancer on a broad gene panel found something inheritable in one in six, and more than a third of them would not have been offered the test under the guidelines then in force.

## Summary

A cross-sectional study of 3,607 men with a personal history of prostate cancer who underwent germline genetic testing between 2013 and 2018, unselected for family history, stage of disease or age at diagnosis, at an accredited diagnostic laboratory. Six hundred and twenty men, 17.2%, had a positive result, defined as a pathogenic, likely pathogenic or increased-risk variant, and only 30.7% of those were in BRCA1 or BRCA2. Positive variants in HOXB13, a gene associated only with prostate cancer risk, were identified in 30 patients, 4.5% of those with a positive result. DNA mismatch repair variants with substantial known therapeutic implications were detected in 1.74% of the total population tested. Examination of self-reported family histories indicated that 229 men with positive variants, 37%, would not have been approved for genetic testing under the National Comprehensive Cancer Network genetic and familial breast and ovarian guidelines then applying to prostate cancer.

## Fields

- Kind: Key paper
- Last checked: 2026-09-25
- Journal: JAMA Oncology
- Year: 2019
- DOI: 10.1001/jamaoncol.2018.6760
- Authors: Nicolosi P, Ledet E, Yang S, et al.
- Findings: Positive germline variants in 620 of 3,607 men, 17.2%, on a broad panel.; Only 30.7% of positives were in BRCA1 or BRCA2.; Mismatch repair variants with therapeutic implications in 1.74% of all men tested.; Thirty-seven per cent of men with a positive result would not have qualified for testing under the guideline in force.
- What it means: It is the second half of the argument for unselected germline testing, and it widens the target beyond BRCA: two thirds of the actionable inherited findings in prostate cancer are in other genes, including the mismatch repair genes that open a checkpoint inhibitor route.
- Caveats: A referral cohort tested at a commercial laboratory, so ascertainment is not random and the 17.2% is higher than a population figure would be.; Increased-risk variants were counted alongside pathogenic ones.; Family histories were self-reported.

## Sources

- Nicolosi et al., JAMA Oncol 2019: germline variants in 3,607 men with prostate cancer referred for testing, against the testing guidelines: https://doi.org/10.1001/jamaoncol.2018.6760
- PubMed: https://pubmed.ncbi.nlm.nih.gov/30730552/

## Connected records

- cancers: [Prostate cancer](https://onco.cc/cancers/prostate/)
- technologies: [Germline (hereditary) testing](https://onco.cc/technologies/germline-testing/)
- targets: [ATM](https://onco.cc/targets/atm/), [BRCA1 / BRCA2 (HRD)](https://onco.cc/targets/brca/), [CHEK2](https://onco.cc/targets/chek2/), [MLH1](https://onco.cc/targets/mlh1/), [MSH2](https://onco.cc/targets/msh2/)
- pathways: [DNA damage response & homologous recombination](https://onco.cc/pathways/ddr/), [Double-strand break repair: HR versus end joining](https://onco.cc/pathways/homologous-recombination-repair/), [Mismatch repair & microsatellite instability](https://onco.cc/pathways/mismatch-repair-msi/)
- terms: [Germline BRCA mutation (gBRCA)](https://onco.cc/terms/gbrca-mutation/), [Germline vs somatic mutations](https://onco.cc/terms/germline-vs-somatic/), [Lynch syndrome](https://onco.cc/terms/lynch-syndrome/), [Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)](https://onco.cc/terms/msi/)
- journals: [JAMA Oncology](https://onco.cc/journals/jama-oncology/)
- biomarkers: [Germline BRCA1/2 pathogenic variant (gBRCAm)](https://onco.cc/biomarkers/brca-germline/)

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