April 11, 2025
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Hereditary Diffuse Gastric Cancer (HDGC) remains a significant subject of genetic research, accounting for 1% to 3% of all gastric cancers. Understanding the role of CDH1 gene mutations in HDGC is critical for advancing both early detection and targeted intervention strategies.
In this blog, we will explore the implications of CDH1 gene testing, the risks associated with HDGC, and the latest research methods that guide scientists and researchers in studying these mutations.
HDGC (Hereditary Diffuse Gastric Cancer) is a rare form of stomach cancer, specifically signet-ring cell adenocarcinoma (SRCC), which develops deep within the stomach lining. This cancer often goes undetected until it’s in an advanced stage, as it doesn’t form visible tumors early on. It’s primarily caused by mutations in the CDH1 gene, leading to abnormal cell growth and increased cancer risk.
People with HDGC may also face higher risks of lobular breast cancer and potentially colorectal SRCC, both of which are associated with poor survival rates.
HDGC is caused by a CDH1 gene mutation, which leads to abnormal cell growth and increases the risk of stomach cancer. But it’s not just about stomach cancer. People with HDGC also have an increased susceptibility to other conditions, like cleft lip or palate, and even other types of cancer.
HDGC follows an autosomal dominant hereditary pattern, which means if a parent has the CDH1 mutation, each child has a 50% chance of inheriting it. This is why family history plays such a huge role in identifying the risk early on.
Also, females with a CDH1 mutation face a 13.6%–33% risk of developing gastric cancer and a 36.8%–55% risk of developing lobular breast cancer by age 80.
CDH1 gene testing is recommended for those who meet specific personal or family history criteria, according to the International Gastric Cancer Linkage Consortium's (IGCLC) 2020 guidelines.
Also, you must note that Intestinal-type gastric cancers and non-lobular breast cancers are not considered for testing criteria, even if confirmed. If CDH1 genetic testing doesn’t reveal a pathogenic variant, CTNNA1 genetic testing is recommended.
The process of conducting the CDH1 genetic testing involves the following steps:
1. Pre-test Counseling: Mapping Family Health Tree
Before the test, the patient sits down with a genetic counselor or a doctor who will walk them through their family health history. This helps build a family health tree and ensures the test is the right choice for them.
2. The Spit/Swab Moment: Simple DNA Collection
No need for needles! The DNA collection is simple – the patient either spits in a tube or provides a cheek swab. It’s quick, painless, and doesn’t require any special prep.
3. The Waiting Game: 2-4 Weeks for Life-Changing Results
Once the sample is submitted, the waiting begins. Usually, patients have their results in 2-4 weeks.
4. Multistep Genetic Counseling Protocol
After the results come in, the patients generally meet again with a genetic counselor to discuss what the findings mean. They guide through any next steps and help understand options moving forward.
5. Comprehensive CDH1 Analysis
The lab will run a full CDH1 analysis, looking for mutations, deletions, or duplications in genes. This step ensures a thorough check for any potential issues.
6. CTNNA1 Testing (if needed)
If no CDH1 mutation is found but patients still meet the criteria, CTNNA1 testing will be the next step for a more comprehensive view of their genetic risk.
Although the process may seem daunting, each step is designed to provide clear, actionable information about health and cancer risks.
If the CDH1 test comes back positive, there are several management strategies. Here’s what to consider:
The most effective defense against gastric cancer for people with a CDH1 gene mutation is prophylactic gastrectomy, removing the stomach before cancer can develop.
This is especially important because signet-ring cell adenocarcinoma (SRCC) can grow without forming visible tumors, making it hard to detect early. By removing the stomach, doctors can reduce the risk of cancer in these patients.
If you’re not ready for surgery, annual endoscopies with special stain technology can help catch any early signs of cancer. It’s important to stay on top of regular screenings for early detection.
But even with these tests, many early-stage cancers can still be missed, so relying solely on endoscopies to delay surgery isn't recommended.
For females with a CDH1 mutation, breast cancer risk is also a concern. It is recommended to begin annual breast MRIs starting at age 30 to catch any potential issues early.
The choice is yours when it comes to preventive surgery—whether it's breast removal or other preventive measures. The timeline is flexible, but staying proactive about your health is key.
Common Recommendations:
While CDH1 mutations primarily increase the risk of gastric and breast cancers, there are other health concerns to keep in mind:
1. Slightly Higher Colon Cancer Risk
People with HDGC may have a slightly higher risk of colon cancer. The good news? Regular screenings can catch it early and reduce the risk of complications.
2. Cleft Lip/Palate Links
Some families with CDH1 mutations also see an increased incidence of cleft lip/palate. If they have such a family history, it’s important to factor it into the health plan.
3. Nutrition Challenges Post-Surgery
After a gastrectomy, there are significant nutrition challenges. Without a stomach, digesting food becomes more difficult, so patients need ongoing nutritional support and adjustments to their diet.
Key Health Management Tips:
Managing health after a CDH1 mutation diagnosis means looking at the big picture, not just cancer risks. Regular screenings, nutrition management, and personalized care are key to staying healthy.
The CDH1 mutation carries a 50% inheritance risk for first-degree relatives. Genetic counseling is essential for understanding how the mutation may affect family members and what steps they should take.
Prenatal Testing & Ethical Considerations
Prenatal testing can determine if the baby has inherited the mutation. This brings up important ethical questions, such as whether to proceed with the pregnancy if the mutation is detected.
Cascade Testing
If a family member tests positive for CDH1, cascade testing can help identify other relatives at risk.
Key Considerations:
Family planning decisions are deeply personal and should be made with careful consideration, support, and expert guidance.
The field of HDGC and CDH1 gene testing is advancing rapidly with new technologies and innovations that promise better detection, treatment, and prevention. Here are some of the exciting developments:
1. Liquid Biopsy: Non-Invasive Early Detection
Instead of invasive tissue biopsies, liquid biopsy technology is emerging as a game-changer.
Grail, a U.S.-based company, is leading the way in cancer research with its methylation-based technology. By analyzing cell-free DNA (cfDNA) from blood samples, it detects cancer signals and tracks tumor burden using methylation patterns. This non-invasive method is particularly valuable for post-diagnosis monitoring, allowing for early detection of recurrence and treatment response.
Widely used by bio-pharma companies, Grail’s technology enables longitudinal monitoring without the need for invasive tissue biopsies. It’s a breakthrough in cancer care, paving the way for smarter, more accurate surveillance and early detection.
2. AI and Personalized Medicine
Artificial intelligence (AI) is enhancing personalized medicine by helping create tailored treatment plans.
PathAI, a leader in AI-powered diagnostics, has launched TumorDetect, a solution that automates tumor assessment and prioritizes cases in pathology labs. Using AI to analyze whole slide images (WSIs), TumorDetect identifies potential tumor areas, allowing pathologists to focus on the most critical cases.
This technology speeds up cancer diagnosis, improving turnaround times and streamlining processes like IHC testing. By highlighting tumor hotspots with visual overlays, TumorDetect enhances precision, making cancer diagnostics faster and more efficient. It's a major leap forward in automating and improving pathology workflows.
3. Improved Surveillance Techniques
Chromoendoscopy and molecular markers are helping doctors spot cancer earlier by improving visualization during endoscopic exams. These advancements help monitor patients with CDH1 mutations more effectively.
4. Genotype-Phenotype Correlation Studies
Researchers are studying how genetic mutations (genotype) correlate with the development of diseases (phenotype). These studies are paving the way for more accurate risk predictions and better management strategies for HDGC patients.
5. Targeted Therapies Under Investigation
There’s growing interest in targeted therapies that focus on the specific genetic mutations causing HDGC. Ongoing research aims to develop treatments that directly address CDH1 mutations, offering new options for patients with HDGC and related cancers.
These emerging technologies promise to revolutionize the way we approach HDGC and CDH1 gene testing, bringing better outcomes and more personalized care for those at risk.
Hereditary Diffuse Gastric Cancer (HDGC) and CDH1 gene mutations are serious risks, but early detection can make all the difference. Genetic testing helps identify these risks and guide preventive actions like gastrectomies and regular screenings.
As emerging technologies like liquid biopsies and AI-powered diagnostics are transforming, it is important to stay ahead with advanced tools and tailored strategies to manage genetic risks. This is where Biostate AI comes in.
Biostate AI offers affordable, high-quality RNA sequencing and multiomics data collection, giving you a deeper insight into your health at unprecedented prices. With services like Total RNASeq for $80/sample and a comprehensive approach to longitudinal change and multi-organ impact, Biostate AI is helping scientists and researchers make faster, more accurate discoveries.
Ready to see how Biostate AI can elevate your research? Get a quote today and explore the future of multi-omics research—your next breakthrough is just a click away!
Testing positive for the CDH1 mutation can cause anxiety and concern for both the individual and their family. Genetic counseling offers essential emotional support and guidance throughout the process.
CDH1 gene testing is highly reliable when done at certified labs. However, rare mutations may not always be detected, so further tests, like CTNNA1 testing, may be recommended if results are negative but risk factors still exist.
The cost of CDH1 testing varies, but it generally ranges from a few hundred to over a thousand dollars. Check with your insurance provider, as it may cover testing based on medical criteria.
Yes, but there’s a 50% chance of passing the mutation to your children. Prenatal testing and genetic counseling can help you explore your options for family planning.
