Hereditary Diffuse Gastric Cancer (HDGC) is an inherited condition that can run in families.
People with HDGC have an increased risk of developing both gastric (stomach) and lobular (an uncommon type) breast cancers.
Many individuals with HDGC will develop stomach cancer by 70 years of age. For those who have a close family member who previously had a stomach cancer, the risk is as high as 60% of women and 70% of men – that is 6-7 out of 10 people with a CDH1 mutation. For those people with no family history of stomach cancer, the risk may be slightly lower. It is rare to develop gastric cancer before 20 years of age even with a gene mutation.
There are usually no symptoms to alert you that you have early gastric cancer. Some people develop nausea, feeling full or bloated after eating, heartburn or indigestion, persistent abdominal pain, difficulty swallowing, weight loss or tiredness. These symptoms can be caused by other conditions and if they are caused by stomach cancer, the disease is often advanced.
Females with a CDH1 mutation are more likely to develop ‘lobular’ breast cancer. By 70 years of age, as many as 40% (4 in 10 females with a CDH1 mutation) will develop a breast cancer. The risk in men appears to be very low. It also appears to be low in CTNNA1 mutations.
There may be no symptoms to alert you that you have early lobular breast cancer but you may notice a lump in your breast, or abnormal changes such as dimpling of the skin, a change in the size or shape of one breast, changes to the appearance of a nipple or discharge from a nipple.
In HDGC part of the CDH1 gene is altered, so it cannot do its job properly. The CDH1 gene makes a protein called e-Cadherin, which helps cells stick together to build a smooth lining to the stomach. People with HDGC have one working copy and one altered copy of the CDH1 gene. When e-Cadherin malfunctions, cells can start to look misshapen (signet ring cells) and they can separate from the stomach lining (islets of signet rings). Eventually, this can develop into diffuse gastric cancer, though exactly why this happens for some and not all people in this situation, is unclear. A similar process is thought to occur in the breast leading to lobular breast cancer.
When you have HDGC, each of your children has a 1 in 2 (or 50%) chance of inheriting it.
Diffuse gastric cancer is a rare form of stomach cancer, but most of the time it is not due to a gene mutation. If several people in a whanau develop diffuse gastric cancer, or at a young age (less than 50), or if there have been both breast and stomach cancers in the same whanau, then this may be due to HDGC.
The gene involved in HDGC (called CDH1) is like a very long instruction sentence. A spelling mistake or alteration in parts of this instruction can affect the way the e-Cadherin protein is assembled. Each family with HDCG will have a different alteration but the individuals within the family will have the same alteration (mutation). A blood sample from someone who has HDGC can be tested to find their specific mutation. If we do find a mutation, we can test other family members to see if they have inherited it or not.
We recommend that children have a genetic test in their late teens (around the age of 16-18 years) to see if they have inherited the altered gene. If they have not inherited the altered CDH1 gene, they do not need HDGC related health checks, but if they develop stomach or breast symptoms then like anybody else they need to see their GP for investigation. Individuals who have not inherited the altered CDH1 gene will not be able to pass the altered gene on to their children in the future.
If an individual has inherited the altered CDH1 gene, it is important that they have stomach checks every year, starting from around 16-18 years of age, and breast checks every year from the age of 30 years.
Stomach cancers can often be found by passing a slim camera through your mouth and into your stomach (a gastroscopy). Samples of the stomach (biopsies) are also taken to look for very early changes. Diffuse gastric cancers usually grow by spreading out through the stomach wall, rather than as an easily seen lump or polyp. Many times early detection can help guide treatment options, but early changes are very difficult to find and can be missed. Unfortunately there is no reliable way of finding all early gastric cancers.
Mammograms (x-ray examinations of the breasts) can find most types of breast cancer. HDGC is associated with lobular breast cancers, which grow by spreading out through the breast, rather than as an easily seen lump, and can be hard to see on mammograms. MRI scans of the breast finds more of these lesions, so from the age of 30 women are advised to have both mammograms and MRI scans of their breasts.
Many people with HDGC are advised to have surgery to remove the stomach or breasts, if there is a high risk of developing cancer. In some situations regular monitoring alone is appropriate.
A total gastrectomy is an operation where the stomach is removed, and the food pipe is connected directly to the small bowel that absorbs all the nutrients. This is similar to operations done to help patients lose weight. It is a big operation, and your doctors will talk to you about whether it is appropriate for you to consider, when in your life circumstances might be the best time to have surgery, and what to expect.
Some women with HDGC choose to undergo risk-reducing mastectomy. This is an operation where breast tissue is removed before breast cancer develops. There are several ways of recreating the breast appearance, including breast implants or tissue flaps.
Many people in New Zealand have an infection with H Pylori in their stomach. This organism can increase the risk of stomach ulcers or stomach cancer. We recommend it is treated with antibiotics. A stool test is very reliable way of finding if you have that infection, and insuring it has been successfully treated.
At the moment there is no known effect of diet on those with HDGC. We recommend a healthy diet and lifestyle including maintaining a healthy weight. Healthy foods include fruit, vegetables, cereals, bread (whole meal), pasta, rice, olive oil and low-fat dairy food such as yoghurt. Possible harmful foods are excessive amounts of animal fat, processed meats (ham, bacon, sausage, hot dogs etc. ), large quantities of red meat.
There is convincing evidence that smoking tobacco increases the risk of many cancers, including gastric cancer. We would also recommend you do not vape long term.
There is convincing evidence that drinking any alcohol increases the risk of many cancers, including stomach and breast cancers. The recommendation for the general population is to avoid binge drinking, stick to less than 2 standard drinks a day, and have at least two alcohol free days a week. For people with a tendency towards cancer development, drinking less than this is recommended.
For more information on diet Click Here
There is currently no evidence that medication is helpful in preventing the progression of cancer in HDGC. This is an area of ongoing research.