Is prostate cancer (PCa) risk elevated in individuals with BRCA mutations? What is the potential of polygenic risk score (PRS) in PCa screening? Experts explored these topics during “Plenary Session 8: Hereditary genito-urinary cancers” held on day 3 of EMUC25.
On BRCA mutations
In her presentation on BRCA, medical oncologist and EMUC25 Steering Committee member Dr. Elena Castro (ES) stated that lifetime prostate cancer (PCa) risk is significantly elevated in individuals with BRCA mutations, with estimates of approximately 17% for BRCA1 carriers and up to 40% for those with BRCA2. Due to this higher risk, annual PSA screening beginning at age 40–45 is recommended for BRCA2 mutation carriers. In contrast, there is currently no clearly established screening guideline for individuals with BRCA1 mutations.
Germline BRCA2 is considered an adverse prognostic factor in PCa, while the impact of BRCA1 is less well defined. Patients with PCa who harbour BRCA1 or BRCA2 mutations benefit from close clinical monitoring. Importantly, germline BRCA1 and BRCA2 alterations sensitise tumours to PARP inhibitors.
Men with high-risk localised, locally advanced, or metastatic PCa should be offered germline genetic testing. Currently, there are no clinical characteristics to identify mutation carriers. Dr. Castro added that when a BRCA1 or BRCA2 mutation is detected in tumour tissue, germline origin should be excluded.
PRS for PCa screening
In her presentation “Polygenic risk to guide prostate cancer screening”, oncogenetics research nurse consultant Dr. Elizabeth Bancroft (GB) discussed the potential of using PRS in PCa screening.
PRS is used to estimate an individual’s genetic predisposition to developing a certain disease. However, it only provides the probability, not a prediction. A higher PRS means a higher genetic predisposition to the disease relative to others in the population, and it can be used to risk-stratify populations.
PRS is calculated by summing the effects of single nucleotide polymorphisms (SNPs), which are the most common type of genetic variation among people. There are 451 SNPs identified that are associated with PCa.
Dr. Bancroft discussed the BARCODE1 study, which evaluated the use of PRS (~130 SNPs) to identify those at the highest risk. Those participants in the top 10% were offered PSA, MRI, and prostate biopsy. The BARCODE1 study concluded that PRS found a high proportion of clinically significant PCa in men at higher genetic risk. PSA and MRI missed some significant cancers in this high-risk group.
“PRS is a one-time test using germline DNA, which is constant, unlike other tools such as PSA, which can fluctuate,” stated Dr. Bancroft.
Furthermore, the PRODICT study, which will replicate BARCODE1, was recently launched with an enriched recruitment in Black African, Black Caribbean, East Asian and South Asian populations.
Pathologist Prof. Markus Eckstein (DE), urologist Prof. Juan Gómez Rivas (ES), oncologist Dr. Pasquale Rescigno (GB), radiation oncologist Dr. Noelia Sanmamed (ES), and radiologist Prof. Harriet Thoeny (CH) spearheaded the session.
For more information, you can (re)watch the presentations via the EMUC25 Resource Centre.
