Rare genetic mutations and prostate cancer in men on active surveillance

Categories: Winter 2023
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Pathogenic germline mutations in certain genes can increase the risk of aggressive prostate cancer (PC). Researchers sought to find out how common these mutations are in men with low-risk PC who are under active surveillance. The authors also wanted to see if these mutations are linked to changes in cancer grade, recurrence, or metastases in men who receive treatment after active surveillance.

The study evaluated men who were part of the Canary Prostate Active Surveillance (AS) Study (PASS). They checked their germline DNA for mutations using a cancer gene panel. The mutations were classified following the American College of Clinical Genetics and Genomics’ guidelines. Scientists used statistical models to check if these mutations were connected to changes in cancer grade or other unfavorable characteristics.

In total, 29 out of 437 (6.6%) participants in the study had a pathogenic germline mutation, and 19 of them were in genes related to DNA repair (4.3%). Eight participants (1.8%) had pathogenic germline mutations in three genes linked to aggressive prostate cancer: ATM, BRCA1, and BRCA2. They found that having these mutations in genes related to DNA repair did not lead

to more unfavorable characteristics and the carrier rates of these mutations were essentially the same in men whose tumors were or were not subsequently reclassified to a higher grade. The rates of these mutations in ATM, BRCA1, and BRCA2 were similar in men who had changes in cancer grade and those who did not (1.9% vs. 1.8%).

Pathogenic germline mutations in cancer predisposition genes are uncommon in men who have adopted AS for low-risk prostate cancer. These mutations don’t seem to have a noticeable link to changes in cancer grade or unfavorable characteristics.

A limitation to this study is the small sample size of men with germline mutation. The results of this study conflict with a previous report from Johns Hopkins reporting more adverse outcomes of AS for patients with germline BRCA2 mutations.

Cancer Medicine. 2022 April 25. https://doi.org/10.1002/cam4.4778

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