Introduction: About 5-10% of PCa correlate with an inherited susceptibility. Germline mutations in DNA-repair genes (DRG) were found in approximately 5% of localized PCa and in 12% of metastatic castration-resistant PCa. As DRG mutations correlate with PCa aggressiveness there is an urgent need to test individuals suspected to be carriers who most benefit from early diagnosis and personalized therapies. The aim of the present study is to investigate the awareness of risk of PCa in families with germline mutations in DRG.
Methods: This is a prospective, monocentric study of families with DRG mutations. Those families were selected from all families of women with breast and/or ovarian cancer treated in the last 5 years at the Breast Unit of our tertiary University Hospital. To test the awareness of risk of PCa we used the ratio between the number of families (where at least one man was present, who was offered the test for mutation detection) and probands who were really tested. Willingness to be tested was stratified according demographic, educational status and geographical residence. Healthy men with DRG mutations were offered a dedicated annual PCa screening consisting of digital rectal examination (DRE), blood test for Prostate Health Index (PHI) and multiparametric MRI with software assisted target biopsy plus systematic biopsy in suspected cases.
Results: Reviewing the genealogical trees of all breast/ovarian cancer patients who attended our Genetic Counselling Clinic from January 2016 to May 2021, we identified, over 1083 families, 132 positive ones for mutations in DRG. Over 132 families, we found that all the male members of 62 rejected to be tested. The original parent branch of mutation was unknown in 24 families and limited the interest in male relatives. In 9 families no male relatives were present; in 5 families, all men were already tested negative; probands were missed in 8. Finally, we selected 29 families (25%) with at least one male relative willing to be tested. We identified 59 men with a DRG mutation, of whom 27 met the inclusion criteria for screening and started it. Living in Northern Italy, higher educational levels, being married, the presence of offspring and at least one first-degree relative affected with cancer correlated with a higher willingness to be tested (p < 0.05). No correlation between age at genetic counselling and test acceptance was found.
Conclusions: Our analysis showed that only 25% of men with a high-risk of developing PCa accepted a genetic profiling, limiting their access to a dedicated PCa screening. This observation strongly supports the urgent need to implement awareness of genetic risk for PCa within male population.
Source of Funding: This work was supported by AIRC (Associazione Italiana Ricerca sul Cancro), grant number IG 2020 ID 25027