When it comes to cancer, genes can significantly influence an individual’s risk. Hereditary genetic testing provides insight into our genetic code, identifying variations/mutations that may increase the likelihood of developing cancer. But who should seek hereditary cancer testing, and what does the process entail?
Who Should Consider Hereditary Cancer Testing?
Hereditary cancer testing is particularly recommended for individuals with a strong family history of cancer, especially those with relatives diagnosed at an early age or those with multiple family members affected by the same type of cancer or the cancers that come under a syndrome.
According to the NCCN (National Comprehensive Cancer Network) guidelines, individuals with multiple relatives diagnosed with cancer—especially at a young age—or those with a family history of certain cancer types should consider genetic testing.
The NCCN guidelines also suggest that individuals without a known family history but who present with early-onset cancer or multiple primary tumors should consider genetic testing. This proactive approach is supported by research that highlights the value of genetic testing in identifying mutations that may not be apparent through family history alone, enabling better-informed healthcare decisions.
Germline Testing is the gold standard for high-risk individuals
The BRCA1/2 mutation, which is well-known for its link with breast and ovarian cancer, a mutation in one of these genes might increase your lifetime chance of developing breast cancer by up to 40-60%. Knowing this enables early surveillance, preventative surgical options , and even tailored medicines, which may significantly lower your risk.
Who Has the Authority to Prescribe Genetic Tests?
A genetic test is typically prescribed by healthcare professionals with specialized expertise, such as oncologists or genetic counselors. These specialists can evaluate your risk based on your personal and family history, and then walk you through the testing procedure.
Genetic counseling, in particular, is crucial. A genetic counselor can help you understand the implications of testing, prepare you for potential outcomes, and provide the information needed to help you make informed decisions.
This step is vital because genetic testing isn’t just about identifying risk; it’s about understanding your options and deciding what to do with that information.
Types of Hereditary Testing: When it comes to hereditary testing, several methods are available, each with its own strengths:
- Next-Generation Sequencing (NGS): This is the most comprehensive method, allowing for the simultaneous analysis of multiple genes. It’s especially useful for individuals who want to cover multiple genes and have a complex family history or multiple cancers.
- Multiplex Ligation-dependent Probe Amplification (MLPA) is used to detect copy number variations, such as deletions or duplications in specific genes. The method is particularly useful in identifying large copy number variations in hereditary conditions like BRCA1/BRCA2 mutated breast and ovarian cancer, providing crucial diagnostic insights.
- Mutation-Specific Testing (MST) targets specific known mutations by amplifying and analyzing predefined DNA regions. It is used for diseases with well-characterized mutations, like BRCA1/2 in breast cancer. Unlike NGS, which can survey multiple genes or the whole genome/exome, or MLPA, which detects large deletions and duplications, MST focuses on identifying and confirming pre-identified mutations.
Each of these testing modalities has a role in a comprehensive genetic examination that is tailored to the individual’s risk profile and medical history.
Expanded Panels vs. Focus Cancer Panels: Which to Choose?
When choosing a genetic test, one of the key decisions is whether to opt for an expanded panel or a targeted cancer panel.
- Expanded Panels: These cover a broad range of genes and are ideal for individuals with a complex family history or multiple types of cancer. They offer a more comprehensive analysis but can sometimes lead to uncertain findings, known as variants of uncertain significance (VUS).
- Targeted Cancer Panels: These are more targeted, analyzing specific genes known to be associated with certain cancers, such as the Hereditary Breast and Ovarian Cancer (HBOC) panel. Focus panels are particularly useful when there is a strong suspicion of a specific hereditary cancer syndrome.
- When to Use MLPA and MST: Critical Scenarios
While they aren’t first-line testing, MLPA and MST are employed in particular situations where alternative approaches might not work well.
- MLPA: It is useful for detecting extensive deletions or duplications in genes that might be missed by standard sequencing. For example, when BRCA1/2 testing is negative but the clinical suspicion is still strong, this test is frequently used as a follow-up. MLPA can find significant mutations that NGS could not technically cover. It is therefore an essential tool for making sure that no important mutations are missed.
- Strand Life Sciences’ NGS germline panels, with 450x depth, provide an additional layer of sensitivity to detect even the smallest mutations. A study of 300 samples evaluated for BRCA1/2 mutations revealed that 209 were BRCA-negative. These samples were subsequently tested using MLPA, which revealed just one positive occurrence of a significant mutation. This study emphasizes the value of high sensitivity, high coverage germline testing to detect mutations that might otherwise require further confirmatory testing.
- MST: Mutation-Specific Testing (MST) focuses on detecting known mutations linked to specific diseases for example BRCA1/2 mutated breast cancers. It involves amplifying and sequencing targeted DNA regions to identify predefined genetic variants. MST is particularly useful for confirming known variants in hereditary conditions such as BRCA1/2 mutations in breast cancer.
What Should You Do If the Report Is Positive?
It can significantly alter one’s life if a hereditary cancer test is positive. However, it is crucial to keep in mind that a positive result is a risk factor that guides your subsequent actions rather than a diagnosis.
Speaking with a genetic counselor and your healthcare practitioner should be your first course of action. They will assist you in understanding your genetic test results and evaluating recurrence risk, provide options for enhanced surveillance, and guide you on potential strategies which could include risk-reducing surgical options or lifestyle changes, and recommendations for family testing..
The Future of Hereditary Testing
Hereditary testing is more than just a glimpse into your genetic makeup—it’s a powerful tool for cancer prevention and personalized medicine. As research advances, so does our ability to detect and manage hereditary cancers. The depth and accuracy of modern tests, such as those using NGS and MLPA, ensure that we catch even the most elusive mutations, providing patients with the information they need to make informed decisions about their health.
With ongoing studies and technological advancements, the future of hereditary testing looks promising. By staying informed and proactive, we can all take steps to reduce our cancer risk and live healthier lives.