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Screening for prostate cancer is one of the most controversial topics in the urological literature. The European Association of Urology supports measures to encourage appropriate prostate cancer detection through PSA testing while reducing overdiagnosis and overtreatment. Additionally, all professional guidelines recommend that age, family history, and race/ethnicity be considered to men at increased risk. However, recent data suggest that this standard of care by itself is insufficient and inadequate.
Prostate cancer risk has significant heritability – 57% (1). Family history is an indirect measure and has a fundamental limitation in that it is based on the current status of related family members and not the genetic makeup of that individual.
Advances in DNA sequencing technologies and identification of prostate cancer susceptibility genes and variants have now provided direct and feasible mechanisms to measure inherited risk.
High-penetrance genes (HPGs) mutations (BRCA1, BRCA2, ATM, CHECK2, etc.) are rare, but their carriers have a significantly higher (2–4 fold) risk of developing prostate cancer in their lifetime compared to the general population. Their testing should be done in healthy men with a history of HPGs in their biologic relatives or according to the specific prespecified criteria.
Most prostate cancer heritability is polygenic. More than 160 prostate cancer risk-associated SNPs have been identified through genome-wide association studies in the last decade. The evidence for the association of these SNPs with prostate cancer risk is strong and reproducible. In contrast to HPGs, risk-associated SNPs are common, but each has a small individual effect on disease risk but have a stronger cumulative effect in a polygenic risk score (PRS). The evidence and performance of PRS for predicting prostate cancer risk is stronger than family history.
AntePC is developed as a genetic test that measures men’s personal risk of developing prostate cancer using a polygenic risk score. AntePC is one of the bases for the early detection of prostate cancer. The purpose of the AntePC test is to reduce the risk of premature mortality due to prostate cancer by more accurate screening.
Clinical recommendations based on AntePC are based on evidence-based data on prostate cancer risk factors, screening and preventive measures, and the corresponding recommendations of international medical organizations, which are adapted to the individual risk level resulting from the test.
- Mucci LA, Hjelmborg JB, Harris JR, Czene K, Havelick DJ, Scheike T, et al. Familial Risk and Heritability of Cancer Among Twins in Nordic Countries. Jama. 2016;315(1):68-76.
- Callender T, Emberton M, Morris S, Eeles R, Kote-Jarai Z, Pharoah PDP, et al. Polygenic risk-tailored screening for prostate cancer: A benefit-harm and cost-effectiveness modelling study. PLoS Med. 2019;16(12):e1002998.
- Na R, Labbate C, Yu H, Shi Z, Fantus RJ, Wang CH, et al. Single-Nucleotide Polymorphism-Based Genetic Risk Score and Patient Age at Prostate Cancer Diagnosis. JAMA Netw Open. 2019;2(12):e1918145.
- Xu J, Labbate CV, Isaacs WB, Helfand BT. Inherited risk assessment of prostate cancer: it takes three to do it right. Prostate Cancer Prostatic Dis. 2019.