Predisposition to prostate cancer and clinical implications in a real-life cohort

Julie Chartier; Albain Chansavang; Anne Jouinot; Nadim Hamzaoui; Arunya Srikaran; Diane Molière; Olivier Huillard; Constance Thibault; Manuela Tiako; Mathilde Sibony; Pierre Laurent-Puig; Eric Pasmant; Camille Tlemsani

doi:10.1038/s41431-025-01859-0

Predisposition to prostate cancer and clinical implications in a real-life cohort

Eur J Hum Genet. 2025 May 6. doi: 10.1038/s41431-025-01859-0. Online ahead of print.

Authors

Julie Chartier¹, Albain Chansavang^{2

3}, Anne Jouinot³, Nadim Hamzaoui^{2

3}, Arunya Srikaran¹, Diane Molière⁴, Olivier Huillard¹, Constance Thibault⁵, Manuela Tiako¹, Mathilde Sibony⁶, Pierre Laurent-Puig^{4

7}, Eric Pasmant^{2

3}, Camille Tlemsani^{8

9}

Affiliations

¹ Department of Medical Oncology, Hôpital Cochin, Paris Cancer Institute CARPEM, Université Paris Cité, APHP.Centre, Paris, France.
² Department of Genomic Medicine of Tumors and Cancers, Fédération de Génétique et Médecine Génomique, Cochin Hospital, Université Paris Cité, APHP.Centre, Paris, France.
³ Institut Cochin, INSERM U1016, CNRS UMR8104, Université Paris Cité, CARPEM, Paris, France.
⁴ Institut du Cancer Paris Carpem, AP-HP, Genomic medicine of tumors and cancers department, Fédération de Génétique et Médecine Génomique, Université Paris Cité, APHP.Centre, Paris, France.
⁵ Department of Medical Oncology, Hôpital Européen Georges Pompidou, Paris Cancer Institute CARPEM, Université Paris Cité, APHP.Centre, Paris, France.
⁶ Department of Pathology, Hôpital Cochin, Paris Cancer Institute CARPEM, Université Paris Cité, APHP.Centre, Paris, France.
⁷ Centre de Recherche des Cordeliers, INSERM, CNRS SNC 5096, Université Paris Cité, Paris, France.
⁸ Department of Medical Oncology, Hôpital Cochin, Paris Cancer Institute CARPEM, Université Paris Cité, APHP.Centre, Paris, France. camille.tlemsani@aphp.fr.
⁹ Institut Cochin, INSERM U1016, CNRS UMR8104, Université Paris Cité, CARPEM, Paris, France. camille.tlemsani@aphp.fr.

PMID: 40328961
DOI: 10.1038/s41431-025-01859-0

Abstract

Genetic predisposition is identified in 5-10% of prostate cancer patients. Although genetic testing is more frequently proposed, international recommendations are lacking. This study evaluates the impact of germline analysis on management of prostate cancer patients. Retrospective descriptive data were collected from prostate cancer patients who attended oncogenetic counselling between 2018 and 2021. Data included clinical and tumoral characteristics, and genomic analysis. Comparative analysis was performed between patients with germline pathogenic variants (PVs) and non-carriers using non-parametric tests. Fourteen out of the 168 patients (8.3%) had a PV, primarily in DNA repair genes (N = 13/14), including BRCA1/2 (N = 5). Twenty-five patients (14.9%) had variants of undetermined significance. Patients with PVs were more likely to have synchronous metastatic extension (79% vs 43%, p = 0.02) and a Gleason score ≥8 (82% vs 53%, p = 0.11). Significant enrichment of ATM PVs compared to a healthy control cohort was observed with an odds ratio of 32.5 [15.8-67.0] (p < 0.05). Three of five patients with BRCA1/2 PVs received DNA repair-targeted treatment. This cohort provides insights into the impact of oncogenetic counselling on prostate cancer patients' management. It highlights the need to refine referral criteria based on disease stage and Gleason score and to further investigate ATM PVs. The data also underscore the importance of developing a care pathway with clear criteria for germline and/or somatic analysis to improve theranostic outcomes.