Why does cancer occur?
Cancer is caused by changes in a cell’s DNA — its genetic “blueprint.” The majority of these changes occur from external influences, known as environmental factors. However, approximately 5–10% of all cancers are caused by inherited genetic mutations passed down from our parents.¹
Using hereditary breast and ovarian cancer syndrome (HBOCS) as an example, BRCA1 mutations are inherited in an autosomal dominant fashion (Figure 1). As such, each child would have a 50% chance of carrying the mutant BRCA1 gene from a parent, which predisposes them to the development of hereditary cancers. Therefore, the occurrence rate of such cancers in the affected family would be higher than that in a non-affected family. The onset of these cancers may also be earlier compared to the average age of onset of the respective cancers.
Autosomal dominant inheritance: Offspring receives an abnormal gene from only one parent (either the paternal [father] or maternal [mother] line).
How is an hereditary cancer gene inherited?
What are the implications of receiving a gene mutation?
BRCA1/2 mutations, for example, are widely known to increase the risk of breast, ovarian, pancreatic, and prostate cancers. Mutations in many other hereditary cancer related genes can also substantially increase the lifetime risk of a tumor when compared to the general population (Figure 2).²⁻⁵
Commonly Found Hereditary Cancer & Hereditary Cancer Syndromes
• Lynch Syndrome
• Li−Fraumeni Syndrome
• Juvenile Polyposis Syndrome
• Peutz−Jeghers Syndrome
• Cowden Syndrome
• Von Hippel−Lindau Syndrome
Who should take a genetic test for cancer risk?
Those with multiple family members who have cancer
Those with a family member who has multiple cancers, an early-onset cancer, or a rare cancer
Any individual who is concerned about the inherent risk of hereditary cancers and cancer syndromes
This educational material is provided for informational purposes only.
Please consult with your healthcare provider for medical advice.
ABOUT ACT GENOMICS
ACT Genomics is an internationally recognized award-winning cancer solution provider who specialize in tailored treatment plans at any given disease stage — from cancer risk evaluation and strategic treatment selection to drug resistance and recurrence monitoring — based on a patient's personal genomic information.
We offer a cancer risk prediction panel named ACTRisk™ that evaluates 67 NCCN guideline-recommended hereditary cancer-related genes (9 major hereditary cancers and 11 cancer syndromes) to identify the risk of hereditary cancers and cancer syndromes and then provide appropriate risk management recommendations.
ACTRisk™ Technical Specifications
Assay Performed
Sequencing of 67 hereditary cancer related genes
Sequencing Mean Depth
>500×
Turnaround Time
12 working days
(upon receipt of qualified sample and complete requisition form)
9 Hereditary Cancers Covered
Breast cancer
Ovarian cancer
Colorectal cancer
Endometrial cancer
Gastric cancer
Prostate cancer
Pancreatic cancer
Melanoma
Neuroendocrine
Technology
Next-Generation Sequencing (NGS)
Sample Types
Blood
Genetic Varation
• Single-nucleotide variants (SNVs)
• Small insertions and deletions (small InDels)
• Splice site variants
11 Hereditary Cancer Syndromes Covered
Hereditary breast and ovarian cancer syndrome
Hereditary diffuse gastric cancer
Lynch syndrome
Juvenile polyposis syndrome
Peutz–Jeghers syndrome
Familial adenomatous polyposis
MUTYH-associated polyposis
Li–Fraumeni syndrome
Cowden syndrome
Melanoma-pancreatic cancer syndrome
Von Hippel–Lindau syndrome
Note: ACT Genomics services can only be prescribed by doctors. Please speak to your doctor for medical advice.
REFERENCES:
1. NIH, Genetic Testing for Inherited Cancer Susceptibility Syndromes
2. Kuchenbaecker, KB, et al. JAMA. 2017;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)
LIMITATIONS:
1. This test does not provide information of variant causality and does not detect variants in non-coding regions that could affect gene expression. Polymorphisms are not reported. The presence of pathogenic variants in genes not analyzed or with incomplete coverage could not be excluded. Genes with incomplete coverage including ALK, APC, ATR, AXIN2, BMPR1A, BRCA1, CDH1, EPCAM, GALNT12, MEN1, MLH1, MSH2, MSH6, NF1, NF2, NTHL1, PMS2, POLD1, POLE, PTEN, RAD50, RAD51D, RB1, RET, SDHC, SMAD4, STK11, TP53, TSC1 and TSC2 as primer design, pseudogenes and tech error. In addition, LGR analysis in APC exon 7, EPCAM exon1, PMS2 exon9, exon12, exon13, exon14, exon15, RAD51C exon6 and RAD51D exon7 cannot be included due to pseudogene and amplicon design.
2. It is possible that the test may return with no abnormal mutation identified for certain genes or part of the test results may not be available due to the technical limitations of the test itself and/or an individual’s genetic differences even the test has been conducted under standard process. This material (including the test and the results) therefrom are intended for educational purposes only for the use of healthcare professionals and do not replace independent professional judgement. This material (including the test and the results) shall at no time be deemed a diagnostic or medical treatment recommendation to any individual. No representation, warranty, express or implied, is made as to, and no reliance should be placed on the fairness, accuracy, completeness or correctness of the information or opinions which may be contained herein. The test takers shall always consult their healthcare professionals for any enquiries of clinical interpretation of the test results.