Germ line Mutation Incidence in Patients with Prostate Cancer and Additional Cancers

Germline pathogenic variants in predisposition genes, including MSH2, in patients with prostate cancer

Approximately 10-20% of patients with prostate cancer carry a germline mutation, but the relationship between prior cancer history and germline status has not been well studied. This retrospective cohort study uses the Myriad Collaborative Research Registry and includes 42,645 patients tested between 2013 and 2024. Germline mutation prevalence rises from 10% with no prior cancer to 15% with one prior cancer and 18% with two or more (p < 0.001). In adjusted analyses, one prior cancer (OR 1.27) and two or more (OR 1.46) are associated with germline positivity, with the strongest associations for prior ureteral (OR 4.81), bladder (OR 1.56) and colon (OR 1.29) cancers, and MSH2 mutations are elevated among patients with multiple prior cancers. Family history is not significantly associated with germline status.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The ureter and MSH2 signal is consistent with the Lynch syndrome spectrum and is a reminder to take the personal oncological history before ordering the test. The authors acknowledge selection bias, since only patients referred for testing by their providers are included, and call for validation in a risk model before any change to testing criteria. The lack of association with family history is surprising and may reflect how it is recorded in a laboratory registry.

Analysis by Dr Thibaut Benquey