AntePC – Prostate Cancer Polygenic Risk Score Test

Science behind AntePC

• E-mail: info@antegenes.com
• Phone number: +372 5377 8141

Overview and Purpose of the AntePC Test

AntePC is a genetic test that assesses a man’s personalized risk of developing prostate cancer using a polygenic risk score. AntePC is one of the tools 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.

AntePC has been developed as a laboratory test by healthcare and medtech company Antegenes (License number L05386).

AntePC test uses data from single nucleotide polymorphisms (SNPs) in the genome to evaluate the personalized risk of developing prostate cancer. This approach is based on the methodology of polygenic risk scores. SNPs used in the risk score either increase or decrease the risk. AntePC combines the number of risk-increasing and lowering SNPs in the genome and their effects, which are summed up to form an overall estimate. Each SNP has little impact on the overall risk of prostate cancer, but combining the effects of individual SNPs contributes to a clinically significant assessment of the risk of developing prostate cancer. The risk model is based on peer-reviewed international research and has been evaluated and validated using anonymous population data of the Estonian Biobank and UK Biobank.

AntePC is used to determine the carrier status of genetic variants that affect patient’s individual risk and are combined into a polygenic risk assessment and the 10-year probability of developing the disease. Individual patient risk is put into context with the population background data and estimates about the genetic risks of individuals of the same sex, age and nationality. Individual test results are accompanied with actionable follow-up recommendations. The final report also includes information about other clinical risk factors that are not included in the polygenic risk estimation.

The test report is made available to the patient and submitted to the Estonian E-Health system. If the patient has been referred to Antegenes by a healthcare service provider then the results can also be shared with the treating physician.

Target Population

AntePC test is recommended for men between the ages of 40 and 70.

AntePC Test Development

The polygenic risk scores and their risk differentiation estimations were validated using anonymous data from the Estonian Biobank and UK Biobank. Based on large-scale genetic data, various risk prediction models published in the international scientific literature were compared, and the prediction accuracy of the best performing model was evaluated on independent data.

The risk score underlying AntePC was adapted and independently validated for practical use based on Schumacher et al., 2019) (1). AntePC uses 121 prostate cancer-related SNPs to estimate personalized risk scores.

Interpretations based on individual risk scores are dependent on population data. AntePC estimates the distribution of individual risk levels relative to the rest of the population, using the population distribution and the risk differentiation between patients estimated during validation on biobanks data. The patient’s 10-year population-based risk is calculated using Choudhury et al. (2) absolute risk model (2). The absolute risk model applies the risk differentiation estimates from Estonian Biobank. The absolute risk model additionally uses patient sex, age and country based epidemiological background including overall prostate cancer incidence and morbidity, and overall mortality information.

Clinical recommendations of AntePC are based on evidence-based data on prostate cancer risk factors, screening, and prevention measures, and the corresponding recommendations of international organizations that are tailored to the individual risk estimates from the test.

AntePC Test Methodology

AntePC test uses a non-invasive buccal swab method to collect and isolate patient’s DNA.

The genetic material is analyzed either using second-generation genotyping or sequencing based methods. The standard procedure includes the use of Illumina Global Screening Array-24 (GSA) v3.0 chip and Illumina iSCAN sequencer for genotyping. This workflow genotypes the ~762 000 markers on the GSA chip by following the Illumina Infinium HTS (high-throughput screening) protocol (Illumina Inc, http://www.illumina.com; Document # 15045738 v04).

The test can also use information from other microarrays and sequencing approaches that output DNA data broadly covering the human genome.

Antegenes performs the risk assessment based on imputed genotype data. Quality-controlled markers resulting from genotyping are imputed using a 1000G panel with reference to the human genome GRCh37.

AntePC Test Limitations

• AntePC test is not used to diagnose prostate cancer.
• An elevated risk estimated by the AntePC test does not mean that the patient will develop prostate cancer during their lifetime. Also, a moderate or lower risk does not mean that the patient will not develop the disease.
• AntePC test is patient-specific and does not assess the risk of the patient’s family and relatives, i.e. polygenic risk score-based disease risks may not be transmitted directly from parents to children
• AntePC test does not analyze rare pathogenic mutations in single genes that significantly increase the risk of prostate cancer, such as BRCA1, BRCA2, ATM, CHEK2, EPCAM, HOXB13, MLH1, MSH2, MSH6 and others. Therefore, we recommend additional counseling and testing for the monogenic mutations, if:

1. The patient’s biological relative has a monogenic mutation in hereditary breast and ovarian cancer gene (BRCA1, BRCA2).
2. A first- or second-degree biological relative has been diagnosed with breast cancer below 50 years of age, pancreatic cancer, ovarian cancer, metastatic prostate cancer, two or more cases of breast cancer in one person or first- or second-degree male biological relative has been diagnosed with breast cancer;
3. The patient’s biological relatives have had three or more tumors associated with hereditary cancer syndromes;
4. Ashkenazi Jewish origin.

• The AntePC test is based on the most up-to-date scientific data, which may, however, be supplemented and changed in the future as additional information becomes available. The field of genetics is constantly evolving, which may lead to changes in risk assessments over time, as well as changes in test selection recommendations and clinical recommendations based on test results.
• Different polygenic risk scores predicting risks of the same trait may give different estimates of the individual’s risks due to differences in the genetic variants included in the models and their weights.
• The results of this test should be applied in context with other relevant clinical data. In addition to the possible genetic predisposition, other risk factors also influence the risk of prostate cancer.