AnteCRC – Colorectal Cancer

Science behind AnteCRC

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

AnteCRC is a genetic test that assesses an individual’s personalized risk of developing colorectal cancer using a polygenic risk score. AnteCRC is one of the tools for the prevention and early detection of colorectal cancer. The purpose of the AnteCRC test is to reduce the risk of premature mortality due to colorectal cancer by primary and secondary prevention.

AnteCRC has been developed by the healthcare and biotechnology company Antegenes (License number L04685) and is registered CE-marked medical device (IVD).

AnteCRC test uses data from single nucleotide polymorphisms (SNPs) in the genome to evaluate the personalized risk of developing colorectal cancer. This approach is based on the methodology of polygenic risk scores. SNPs used in the risk score either increase or decrease the risk. AnteCRC 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 effect on the overall risk of colorectal cancer, but combining the effects of individual SNPs contributes to a clinically significant assessment of the risk of developing colorectal cancer.

The risk model is based on peer-reviewed international research and has been evaluated and validated using anonymous population data of the UK Biobank.

AnteCRC is used to determine the number of genetic variants that affect a patient’s individual risk and results in a combined genetic risk assessment. The patient’s individual risk is compared with the rest of the population, evaluating the 10-year probability of developing the disease and relative risk compared to the average genetic risk in the population, which is used to interpret the test results together with clinical recommendations.

Recommendations based on the relative risk calculated using the AnteCRC test consider only the polygenic risk component. In addition to test results, recommendations include clinical information about disease symptoms and indications for testing for the monogenic mutations.

Target Population

AnteCRC test is recommended for:

  • Men and women between the ages of 40 and 75 of European descent (Explanation: genetic risk studies used by AnteCRC have been conducted in populations of European descent).

The AnteCRC test is not recommended if:

  • The patient has a monogenic mutation, significantly increasing the risk of colorectal cancer (APC, KRAS, TP53, MLH1, MSH2, MSH6, PMS2, STK11, MUTYH).

Indications for testing for the monogenic mutations:

  • The patient’s biological relative has a monogenic mutation of colorectal cancer (APC, KRAS, TP53, MLH1, MSH2, MSH6, PMS2, STK11, MUTYH);
  • Two or more biological relatives have been diagnosed with colorectal cancer;
  • Biological relatives have had three or more tumors associated with hereditary cancer syndromes.

If these criteria are met, we recommend genetic counseling and, if appropriate, testing for hereditary forms of cancer.

AnteCRC Test Development

Population distribution of the polygenic risk score and risk differentiation were validated using anonymous data from the UK Biobank. Based on large-scale genetic data, various risk prediction models published in the international scientific literature were tested, and the prediction accuracy of the best performing model was evaluated on independent data. Based on the selected risk score, the population distribution on which the comparisons are based on was also created.

The risk score underlying AnteCRC (1) is tailored for practical use and independently validated. After validation, AnteCRC uses 91 colorectal cancer-related SNPs to calculate personalized risk scores.

Interpretations based on individual risk scores are dependent on population data. AnteCRC estimates the distribution of individual risk levels relative to the rest of the population, using the population distribution and the risk differentiation between patients assessed during validation on Estonian Biobank data. The patient’s 10-year population-based risk is calculated using Choudhury et al. absolute risk assessment model (2). The model uses the estimation of risk differentiation from validation on the UK Biobank data as input.

In addition, we use population-based overall mortality and colorectal cancer morbidity and mortality data to assess risks.

Clinical recommendations in AnteCRC test are based on evidence-based data on colorectal cancer risk factors, screening, and preventive measures, and the corresponding recommendations of international organizations, which are tailored to the individual risk level resulting from the test.

AnteCRC Test Methodology

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

The genetic material is analyzed using second-generation genotyping and carried out in the Core Facility of the Institute of Genomics, University of Tartu, which is certified by Illumina CSPro (Certified Service Provider). The Illumina Global Screening Array-24 (GSA) v3.0 chip and Illumina iSCAN sequencer are used for genotyping. The GSA chip has ̴̴762,000 markers. The whole analysis is performed according to the Illumina Infinium HTS (high-throughput screening) protocol (Illumina Inc, http://www.illumina.com; Document # 15045738 v04).

Quality-controlled markers resulting from genotyping are imputed using a 1000G panel with reference to the human genome GRCh37. Based on imputed genotype data, an individual risk score is calculated in the Antegenesis Information System.

The test report is made available to the patient and their treating. Interpretation of the results and clinical recommendations are added to the report.

 AnteCRC Test Limitations

  • AnteCRC test is not used to diagnose colorectal cancer.
  • AnteCRC test is not validated for use by individuals of non-European descent.
  • An elevated risk estimated by the AnteCRC test does not mean that the patient will develop colorectal cancer during their lifetime. Also, a moderate or lower risk does not mean that the patient will not develop the disease.
  • AnteCRC 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.
  • AnteCRC test does not analyze rare pathogenic mutations in genes that significantly increase the risk of colorectal cancer, such as APC, KRAS, TP53, MLH1, MSH2, MSH6, PMS2, STK11, MUTYH and others.
  • The AnteCRC 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 colorectal cancer.

Cost of the test

Please see the “Customer Price List”.

References

  1. Huyghe, Jeroen R., et al. “Discovery of common and rare genetic risk variants for colorectal cancer.” Nature genetics51.1 (2019): 76.
  2. Choudhury, Parichoy Pal, et al. “iCARE: An R Package to Build, Validate and Apply Absolute Risk Models.” bioRxiv(2018): 079954.