Affiliation:
1. Faculty of Medicine Tel Aviv University Tel Aviv Israel
2. Department of Professional Medicine Maccabi Healthcare Services Tel Aviv Israel
3. KSM Research and Innovation Center Maccabi Healthcare Services Tel Aviv Israel
4. Davidoff Cancer Center Rabin Medical Center Petah Tikva Israel
5. BioInsight Ltd. Binyamina Israel
6. Genetic Institute, Maccabi Healthcare Services Rehovot Israel
7. Tipa Biobank, KSM Research and Innovation Center, Maccabi Healthcare Services Tel Aviv Israel
8. The Genomics Unit, Sheba Cancer Research Center Sheba Medical Center Ramat Gan Israel
Abstract
AbstractBackgroundWhole exome sequencing (WES) furthered our understanding of various tumors. We assessed the occurrence of germline likely pathogenic/pathogenic (LP/P) variants, disease features, and clinical outcomes in early‐onset prostate cancer.MethodsThis retrospective study (N = 134) included consecutive prostate cancer patients who donated blood samples for research purposes to the Kahn‐Sagol‐Maccabi biobank. Patients diagnosed at >65 years were excluded. Clinical characteristics were extracted from the medical records. Germline WES was performed with analysis reporting on oncogenetic, two immunogenic, and a secondary minimum list panels (121, 468, 76, and 59 genes, respectively).ResultsMedian age at diagnosis was 61 (range 46–65) years; 131 (98%) were diagnosed with local disease. The median follow‐up time from diagnosis was 14 (range <1–25) years. Of the patients with local disease, 32 (24%) and 10 (8%) had biochemical and distant recurrences, respectively. Twenty‐five patients (19%) had ≥1 additional cancer (excluding non‐melanoma skin cancer), most frequently bladder (6), colorectal (5), and lymphoma (5). Seven (5%) deaths were reported, with only one related to prostate cancer. LP/P variants were identified in 8 patients (6%), all in genes from the oncogenetic panel: ATM, BRCA1 (in two patients), BRCA2 (in two patients), HOXB13, MUTYH, and MYH7. Of these eight patients, with a median follow‐up of 7 years (range <1–15), two (25%) had biochemical recurrences, one had (12.5%) distant recurrence, and no deaths were reported.ConclusionsIn this cohort of 134 early‐onset prostate cancer patients, we identified germline LP/P variants in an oncogenetic panel in 6% of participants, with no unique clinical outcome.