Prostate Cancer Prevention Clinic for Men with Risk of Familial Prostate Cancer

• Applicants: Professor Dr. Peter Albers; Professorin Dr. Dagmar Wieczorek
• Subject Area: Reproductive Medicine, Urology ; Human Genetics
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 514060189

Within the National Cancer Prevention Graduate School, the German Cancer Aid (DKH) funds a newly established Prostate Cancer Prevention Clinic for men with familial risk at Düsseldorf University in collaboration with the DKFZ core unit (National Cancer Prevention Center). This is a unique and first of its kind outpatient clinic which will include about 50-70 men at risk for prostate cancer (PCA) per year (2023-2026) and offer specialized diagnostics (like multiparametric MRI, psychometric tests, laboratory and genetic analysis). Aim is a better management of patient´s anxiety by establishing an individualized risk score with consecutive risk-adapted monitoring. DKH is funding a graduate student who will evaluate the psychometric tests administered in this risk consultation for men at risk for prostate cancer with respect to the development of anxiety. The planned genetic analyses are not covered by funding, but will be the key for development of an individual score and risk-adapted early detection. The University Hospital Düsseldorf (CIO-D as part of the Center for Integrated Oncology, CIO-ABCD) supports this outpatient clinic in terms of personnel. All men will receive genetic counselling including pedigree analyses, clinical investigations and multiparametric specialized MRI of the prostate. After informed consent, all men (index patients or men at risk) will receive diagnostic panel sequencing of dedicated, well-known PCA-related genes in a first step. To date, however, only a few genes have been identified for which an association with PCA is postulated (e.g. BRCA1, BRCA2, HOXB13). Only 15-20% of affected individuals are identified to carry a mutation in one of these genes. It is likely that there are a large number of other PCA risk genes and the understanding of the genetic basis of PCA is only rudimentary to date. It is therefore essential to perform further genetic analyses of blood and/or tumor (exome sequencing, genome sequencing and transcriptome analyses) in men without pathogenic mutations in the few PCA risk genes in a second step with the aim of elucidating the underlying genetic alterations and thus gaining a profound understanding of the mechanisms of tumorigenesis. Only this knowledge will allow to specify the risk for the men/their family members and to transfer them to an appropriate early diagnosis, which is the aim of our prostate cancer risk consultation. To specify the risk based on genetic analyses and clinical/imaging examinations, a genotype-phenotype correlation for men with PCA will be established for mutations in known as well as in newly identified genes. Finally, a scoring system will be developed to calculate a personalized risk for men at increased risk of PCA and subsequently tested and evaluated.

• DFG Programme: Research Grants