ACTRisk™

ACTRisk™

Genetic Testing For Hereditary Cancers

Identifies Hereditary Cancer-related Genes and Cancer Risk

When multiple cases of cancer occur in a family, it is necessary to consider whether the family members are exposed to a shared intrinsic risk factor arising from the inheritance of cancer-related gene mutations.

What are Hereditary Cancers?

Approximately 5–10% of cancers are caused by inherited genetic mutations.In addition to BRCA1/2 mutations, which are widely known to increase the risk of breast, ovarian, pancreatic and prostate cancers, mutations in many other hereditary cancer-related genes also increase the lifetime risk of cancer by up to 90 times compared with that of the general population (Figure 1).2-5

Although hereditary cancers constitute a small proportion of all cancer cases, they should not be overlooked. Many of the cancer-stricken families carry susceptibility or predisposing genes which are passed down the family across multiple generations. Based on the penetrance rate, these genes can be classified as either high penetrance, moderate penetrance or low penetrance.Patients with moderate-to-high penetrance genes are at significantly higher risk of developing cancer. Therefore, in accordance with the recommendations of the American Society of Clinical Oncology (ASCO) and the National Comprehensive Cancer Network (NCCN) guidelines, cancer screening, monitoring and intervention need to be performed early. Indeed, a study in 2017 found that the incidence of colorectal cancer could be reduced if patients with susceptibility gene (e.g., MLH1, MSH2, MSH6, PMS2) mutations underwent regular colonoscopy and polyps removal, which were found to decrease the mortality rate by a staggering 65%.7

How are Cancer Susceptibility Genes Inherited?

Patients with a hereditary cancer usually have a family history of cancer. Therefore, it is important to consider both the paternal and maternal lines of inheritance. Using hereditary breast and ovarian cancer syndrome (HBOCS) as an example, BRCA1 mutations are inherited in an autosomal dominant fashion (Figure 2). As such, each of the siblings or children would have a 50% chance of carrying the mutant BRCA1 gene from the parent, which predisposes them to the development of hereditary cancers. Therefore, the occurrence rate of these cancers in the affected family would be comparatively higher than others. The onset of these cancers may also be earlier compared with the average age of onset of the respective cancers. Because each hereditary cancer has different characteristics, it is highly recommended that genetic counselling is conducted by a trained professional before and after the tests.

References
1. NIH, Genetic Testing for Inherited Cancer Susceptibility Syndromes.
2. Kuchenbaecker KB, et al. (2017) JAMA. 317(23):2402–2416.
3. NCCN Guidelines: Genetic/Familial High-Risk Assessment: Colorectal (2019. V3).
4. NCCN Guidelines: Genetic/Familial High-Risk Assessment: Breast and Ovarian (2020. V1).
5. NCCN Guidelines: Gastric Cancer (2017. V3).
6. Erin F Cobain, et al. (2016) Semin Oncol. 43(5):528–535.
7. Steel E, et al. (2017) Hered Cancer Clin Pract. 15:1.

Hallmarks of ACTRisk™

  1. Provides Information on 67 Types of Hereditary Cancer Genes
    The test can be done with just one blood draw, and a comprehensive evaluation of 9 major hereditary cancers and 11 cancer syndrome genes can be obtained by using whole exome sequencing.

  2. Bioinformatics Analysis Based on International Databases
    Extracts up-to-date information from international databases, namely GnomAD, 1000 Genome, ClinVar, COSMIC and ACT Genomics' in-house ethnographic database.

  3. Genetic Testing with High Accuracy
    Uses next-generation sequencing (NGS) technology to detect various types of mutations such as SNV, Small InDel, Splicing Site and LGR.

  4. Detailed Cancer Risk & Clinical Management Reporting
    Provides the relevant risk information based on the latest international clinical research literature, provides comprehensive risk factors, and is clear and easy to understand.

  5. Short Turnaround Time
    Provides professional solutions within 15 working days (starting from the date of receipt of approved samples at our CAP-accredited laboratory).

Who Should be Tested?

  1. Multiple family members who have cancer.

  2. Any individual who is concerned about the inherent risk of hereditary cancers and cancer syndromes.

  3. A family member who has multiple cancers, an early-onset cancer or a rare cancer.

Technical Specifications

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Number of Genes Tested

67 Hereditary Cancer-related Genes

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Turnaround Time

12 Working Days*

*starting from the date of receipt of approved samples at our CAP-accredited laboratory
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Genetic Variation

∙ Single nucleotide variants (SNVs)
∙ Small insertions and deletions (small InDels)
∙ Specific exon-intron splicing site mutation of selected genes
∙ Large genomic rearrangement (LGR) of 18 genes, including BRCA1/2 and MMR genes.

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Databases Used

∙ International databases such as GnomAD, 1000 Genome, ClinVar and COSMIC
∙ ACT Genomics' in-house ethnographic database built from published evidence

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Specimen Requirements*

4-8 mL whole blood x 2 tubes

*refer to our specimen instructions

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