Male awareness of prostate cancer risk remains poor in relatives of women with germline variants in DNA-repair genes

Vittorio Fasulo; NicolòMaria Buffi; Giuseppe Chiarelli; Giovanni Lughezzani; Monica Zuradelli; Carla Barbara Ripamonti; Monica Barile; Paolo Bianchi; Alessio Benetti; Marco Paciotti; Alessandro Uleri; Pier Paolo Avolio; Alberto Saita; Rodolfo Hurle; Federica Maura; Luca Germagnoli; Rosanna Asselta; Giulia Soldà; Paolo Casale; Massimo Lazzeri

doi:10.1002/bco2.252

Male awareness of prostate cancer risk remains poor in relatives of women with germline variants in DNA-repair genes

BJUI Compass. 2023 Jun 21;4(6):738-745. doi: 10.1002/bco2.252. eCollection 2023 Nov.

Authors

Vittorio Fasulo^{1

2}, NicolòMaria Buffi^{1

2}, Giuseppe Chiarelli^{1

2}, Giovanni Lughezzani^{1

2}, Monica Zuradelli^{1

3}, Carla Barbara Ripamonti⁴, Monica Barile⁴, Paolo Bianchi⁴, Alessio Benetti², Marco Paciotti^{1

2}, Alessandro Uleri^{1

2}, Pier Paolo Avolio^{1

2}, Alberto Saita², Rodolfo Hurle², Federica Maura^{1

4}, Luca Germagnoli^{1

5}, Rosanna Asselta^{1

5}, Giulia Soldà^{1

5}, Paolo Casale², Massimo Lazzeri²

Affiliations

¹ Department of Biomedical Sciences Humanitas University Pieve Emanuele MI Italy.
² Department of Urology IRCCS-Humanitas Research Hospital Rozzano MI Italy.
³ Medical Oncology and Hematology Unit IRCCS-Humanitas Research Hospital Rozzano MI Italy.
⁴ Laboratory Analysis Unit IRCCS-Humanitas Research Hospital Rozzano MI Italy.
⁵ IRCCS-Humanitas Research Hospital Rozzano MI Italy.

Abstract

Abstract.

Objective: The aim of this study is to evaluate male awareness of developing prostate cancer (PCa) in families with germline DNA-repair genes (DRG) variants.

Materials and methods: Data were collected from a prospective, monocentric cohort study. The study was conducted in a university hospital with a multidisciplinary approach to the patient (collaboration of the Departments of Oncology, Urology, Pathology, Radiology, and Medical Genetics Laboratory). We recruited healthy males, relatives of families of women with breast or ovarian cancer who tested positive for pathogenic variants (PVs) or likely pathogenic variants (LPVs) in DRGs. A dedicated PCa screening was designed and offered to men aged 35 to 69 years, based on early visits with digital rectal examination (DRE), prostate health index (PHI) measurement, multiparametric magnetic resonance imaging (mpMRI) and, if necessary, targeted/systematic prostate biopsies. The primary endpoint was to evaluate the willingness of healthy men from families with a DRG variants detected in female relatives affected with breast and/or ovarian cancer to be tested for the presence of familial PVs. The secondary endpoints were the acceptance to participate if resulted positive and compliance with the screening programme.

Results: Over 1256 families, of which 139 resulted positive for PVs in DRGs, we identified 378 'healthy' men aged between 35 and 69 years old. Two hundred sixty-one (69.0%) refused to be tested for DRG variants, 66 (17.5%) declared to have been previously tested, and 51 (13.5%) males were interested to be tested. Between those previously tested and those who accepted to be tested, 62 (53.0%) were positive for a DRG variant, and all of them accepted to participate in the subsequent surveillance steps. The main limitation is that is a single-centre study and a short follow-up.

Conclusions: All men tested positive for a DRG variants agreed to go under the surveillance scheme. However, only 31% of 'men at risk' (i.e., relative of a DRG variant carrier) expressed their willingness to be tested for the familial DRG variant. This observation strongly supports the urgent need to implement awareness of genetic risk for PCa within the male population.

Keywords: BRCA 1‐2; DNA‐repair gene variant; genetic risk; prostate cancer; screening.