Have you heard of hereditary gastric cancer? (Hereditary Diffuse Gastric Cancer - HDGC) Let's talk about this!

Today we are going to talk about a serious condition that many people are not aware of. This is a type of stomach cancer that is hereditary. Doctors call it `(Hereditary Diffuse Gastric Cancer)` or `(HDGC)` for short. If someone in your family has had this condition, or if you want to know more about it, this article will be very important for you. Don't worry, let's talk about it simply.

What is this `(HDGC)`?

Simply put, HDGC is a hereditary cancer risk condition. This means that your lifetime risk of developing stomach cancer (Gastric cancer) is increased by about 70%. Not only that, women who inherit this condition also have a 42% increased risk of developing a specific type of breast cancer , Lobular Breast Cancer (LBC) .

People with this `(HDGC)` condition inherit a mutated gene (`(mutated gene)`) from one of their parents. Most often, this is a gene called `(CDH1)` . But sometimes other genes can be involved. `(CDH1)` is a tumor suppressor gene (`(tumor suppressor gene)`). When this is mutated, it does not work properly to control cancer. Think of it, this gene is like a policeman in our body who stops cancer cells from growing. So what happens if that policeman becomes weak? That's what happens here too.

What is "diffuse" gastric cancer?

Now let's see what this `(Diffuse Gastric Cancer)` is. This is a type of stomach cancer. But instead of growing in one place like other cancers, this one spreads throughout the stomach wall in small clusters of cells. It's like a water leak spreading along a wall. Due to this, the stomach wall thickens and hardens. Gradually, it spreads to the deeper layers of the stomach wall.

This type of stomach cancer is a bit difficult to diagnose because it is not clearly visible on standard imaging tests. Also, symptoms often appear only after the disease has spread, in the later stages. At that point, the cancer may have spread (metastasized) through the stomach wall to nearby tissues, such as the liver or bones.

How common is this condition?

Talking about the condition `(HDGC)`, it is estimated that approximately five to ten people out of ten thousand can inherit this condition at birth. About 20% of all stomach cancers are of the `(diffuse)` type. About 2% of those diffuse cancers are hereditary `(HDGC).` Although stomach cancer is generally more common in Asian countries than in Western countries, this `(HDGC)` condition is reported more frequently in Western countries.

What are the symptoms of `(HDGC)` condition?

As we mentioned earlier, symptoms of this type of diffuse gastric cancer may not appear until the disease has spread (metastasized). That's why it's important to be aware of the risk that this condition can run in families. In HDGC, the cancer develops at a slightly younger age than in other cancers. Most people are diagnosed before the age of 40.

The main symptoms may be:

• Stomach pain (especially in the upper left part of the abdomen)
• Stomach bloating, flatulence
• Nausea and vomiting
• Appetite
• Weight loss
• Extreme fatigue, tiredness
• Difficulty swallowing food
• Blood in poop (`(Blood in poop)`)
• Vomiting blood (`(Vomiting blood)`)
• Jaundice (yellowing of the eyes and skin)

Sometimes, a birth defect called cleft lip or cleft palate can also be an early sign of this syndrome. This is because this genetic mutation can cause this birth defect. However, most of the time, cleft lip is not related to HDGC. However, if you were born with such a birth defect and someone in your family has had these types of cancers, you may be a little suspicious.

What is the reason for the formation of this `(HDGC)`?

HDGC is a genetic disorder . It occurs when a mutation in one of the tumor-suppressing genes we talked about earlier changes the programming in your DNA. Tumor-suppressing genes tell cells to control cell division and growth. So when these genes don't work properly, cancer can develop.

You inherit this mutated gene from either your mother or your father. A mutation inherited in this way is called a germline mutation . It affects the genetic code of your reproductive cells.

How is this `(HDGC)` inherited?

HDGC is an autosomal dominant condition. This means that you only need to have one copy of the mutated gene to inherit the syndrome. It can be inherited from either your mother or your father. If one of your parents has the mutation, you or your siblings have a 50% chance of inheriting it. Think of it like the chance of a coin coming up heads or tails.

Does everyone who inherits the gene mutation develop cancer?

No. The genetic mutation you inherit from your parents affects only one copy of the cancer-suppressing gene in each cell. But every cell has two copies of this gene, one from your mother and one from your father. So even if you don't inherit the same mutation from both parents, you still have a copy of the gene that works normally.

For cancer to develop, a second mutation (`(somatic mutation)`)It must occur in the tissue where the cancer forms (i.e., the lining of the stomach or the lobules of the breast) during your lifetime. This second mutation also deactivates the other copy of the gene. That's when the cancer begins to grow.

What is the cause of this second mutation?

To be honest, we don't know the exact reason for this. But various factors may play a role. Environmental exposures often play a role in "triggering" genetic diseases. Other genes may also be involved. Some families that carry the HDGC gene have a higher incidence of cancer than others.

Some environmental risk factors that contribute to the development of stomach cancer are:

• Smoking
• Excessive alcohol use
• Eating too much red meat (such as beef, lamb)
• (H. pylori) infection (this is a bacteria that causes stomach ulcers)

How is the testing process for `(HDGC)`?

Even if you don't have symptoms yet, if there is reason to think you are at risk (for example, if someone in your family has had these types of cancer, or if you have had a genetic test that found a mutation in the `(CDH1)` gene), a doctor may refer you for testing for `(HDGC)`.

Your doctor will calculate your risk based on your family history and/or genetic test results. They may also look for cancer precursors in your tissues. For example, they may look for a condition called Lobular Carcinoma In Situ (LCIS) in the breast or signet-ring-type cells in the lining of the stomach. These are early changes that can become cancer.

How is HDGC diagnosed?

If you have symptoms of metastatic stomach cancer, your doctor will look for evidence of cancer in your stomach wall. They will take tissue samples and examine them under a microscope. If metastatic stomach cancer is found, and if someone in your family has had this type of cancer, your doctor may suggest that you have genetic testing .

Currently, about 40% of patients with HDGC have been found to have this CDH1 mutation. Other mutations may be involved, but CDH1 is the main one we know of and can identify. If you have it, it is a surefire way to diagnose HDGC. However, if you have a family history of this type of diffuse gastric cancer, you may be diagnosed with HDGC even if you do not have the CDH1 mutation.

What tests are used to diagnose `(HDGC)`?

These tests can be done to diagnose the disease:

• Genetic testing:This is a blood test. A sample of your blood is taken and analyzed to see if there are any genetic mutations associated with genetic diseases. Some people get this test because they have a family history of genetic diseases. Others get this type of genetic test because they don't know their family health history, for their own information, or because they are planning to have children.
• Upper endoscopy (EGD test): This is a test to look at the inside of your upper gastrointestinal tract (i.e., esophagus, stomach) and take tissue samples. This is essential for diagnosing stomach cancer, especially this type of cancer that has spread. A gastroenterologist (a doctor who specializes in gastrointestinal diseases) does this. He or she inserts a long tube (an endoscope) with a small camera through your mouth and down your esophagus into your stomach. Tissue samples can also be taken through the tube. However, even with these methods, it can be difficult to find metastatic stomach cancer. Because it is so widespread, the doctor may not be able to see it or get it in the tissue samples. Therefore, a doctor who looks for this type of cancer must have special training and experience.
• Breast MRI: Because lobular breast cancer is not detected by a regular mammogram, doctors recommend an MRI. If the MRI shows anything unusual, it is marked and another doctor takes a tissue sample.
• Biopsy: The doctor takes a sample of tissue and sends it to a lab to be examined under a microscope. This biopsy can confirm whether the tissue sample contains cancer cells.

What happens after it is identified as having `(HDGC)`?

If you already have cancer, your doctor will talk to you about treatment options. Even if you don't have cancer yet, if you have this syndrome, your doctor will likely recommend regular cancer screening tests, as mentioned above. Preventive surgery is another option you can talk to your doctor about.

How is metastatic stomach cancer treated?

Surgery is usually the first treatment for cancers that can be removed with surgery. If you have HDGC, your doctor will often recommend a total gastrectomy . This is because HDGC has a high risk of spreading far away before it is found.

In a total gastrectomy, the surgeon removes your entire stomach and connects the end of your esophagus directly to your small intestine. It is possible to live without a stomach, but there are some side effects. After surgery, you may have additional treatments (adjuvant therapies) such as radiation therapy or chemotherapy.

Because women with `(HDGC)` are also at risk of developing lobular breast cancer (`(LBC)`), they need to be constantly aware of the symptoms of `(LBC)` during treatment. If you have `(LBC)`, treatment usually starts with breast cancer surgery. Additional treatments are then given.

What is the life expectancy with `(HDGC)` condition?

Life expectancy depends on finding and treating the cancer early. Even with regular screening, this can be difficult. If metastatic stomach cancer is caught and treated early, the five-year survival rate is more than 90%. However, if it is found late, after it has invaded the stomach wall, the rate drops to less than 30%.

That's why we say it's so important to be aware of family history and seek medical advice if you're at risk.

Is there a way to prevent `(HDGC)`?

If you have the `(CDH1)` gene mutation (which is associated with an increased risk of developing cancer), there are several preventive measures you can take. For people without this specific gene mutation, the risks and measures are not clearly defined. You can talk to your doctor about your personal risks and options.

Prophylactic surgery

If you have been diagnosed with HDGC for at least 20 years and have no other major health problems, your doctor may recommend a prophylactic total gastrectomy . Although the loss of the stomach can have some effects on your digestive system, these side effects are easier to manage than dealing with advanced stomach cancer.

For those who are not ready to take these steps, a "wait-and-watch" approach can be adopted, which involves frequent upper intestinal endoscopy and random biopsy samples. However, even with such close monitoring, HDGC may not always be detected early (when treatment is most effective).

Side effects of total gastrectomy:

• Dumping syndrome: When food passes directly from the esophagus into the small intestine, it passes through the small intestine faster than normal. This can cause major changes in the hormones in the digestive system, leading to symptoms such as nausea, diarrhea, and low blood sugar. These symptoms can be controlled by changing your eating habits. These symptoms will subside over time.
• Malabsorption and malnutrition: When the stomach is removed, the part of the stomach that contains the acids and enzymes that help digest food is lost. This can prevent food from being broken down properly and prevent the body from absorbing nutrients. This can lead to malnutrition. This can be helped by changing your diet and taking nutritional supplements.

Genetic counseling and family planning

For people with the CDH1 gene mutation, genetic counseling can be very helpful in discussing family planning. This can help you understand the risk of your child inheriting the HDGC condition. If you are planning to have children, one option to manage that risk is selective In Vitro Fertilization (IVF) .

In IVF, eggs and sperm are taken from the mother and father and fertilized in a lab. After the embryos develop, a single cell from each embryo can be taken and tested for the CDH1 mutation. The parents can choose embryos that do not have the mutation and implant them in the mother's uterus.

Finally, what to keep in mind

Finding out that you have Hereditary Diffuse Gastric Cancer Syndrome (HDGC) can be a very emotional experience, and you may have to make big decisions. These can affect you and your family. Take your time to think things through without panicking. Ask as many questions as you need. Your medical team is here to help you find the best way to navigate this journey. Remember, awareness is the first step. You are not alone.

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