Hereditary Diffuse Gastric Cancer

Blood is the preferred specimen, but saliva can be used as an alternative as your CDH1 genes are most often the same in blood or saliva.

Unfortunately, the current screening for stomach cancer is minimal and often times will miss the cancer at an early stage.

An individual who has a mutation has a 50% chance to pass the mutation that causes hereditary diffuse gastric cancer on to each of their children. The siblings of an individual who has a mutation have a 50% chance to inherit the mutation. Either the mother or father of an individual who carries a mutation are obligate carriers for the mutation. In general, children should not be tested until they are at least 18 years of age. Genetic testing for a hereditary cancer condition is an individual’s choice, and is an option available, but not mandatory, for other family members

To find other people with hereditary diffuse gastric cancer, please visit:

To determine if you are someone who would be a good candidate for genetic testing, meeting with a genetics provider is recommended. You can find a genetic counselor near you at: [link url="www.nsgc.org” target=”_blank”>www.nsgc.org or [link url="www.cancer.gov/cancertopics/genetics/directory” target=”_blank”>www.cancer.gov/cancertopics/genetics/directory.

A gastroenterologist can help manage the stomach screening, and a surgeon is someone you should meet with to discuss the gastrectomy.

The abbreviation for hereditary diffuse gastric cancer is HDGC.

The average age of developing stomach cancer is 38 years old.

Permanent weight loss of 20% of total body weight typically occurs within the first 6 months after a total gastrectomy. Individuals who have their stomach removed are recommended to eat 6-8 small meals a day in order to avoid any symptoms that may occur from food entering the small intestine too quickly.

Hereditary diffuse gastric cancer is a condition that runs in the family and causes an increased risk for certain types of cancer including: stomach cancer, breast cancer, and colon cancer.

A total gastrectomy is complete removal of the stomach.

Symptoms of stomach cancer are generally nonspecific at the early stages. Once symptoms do appear, individuals usually have an advanced stage of the disease. Symptoms in the late stage of gastric cancer may include: nausea, vomiting, abdominal pain, dysphagia (difficulty swallowing), feeling full quickly, loss of appetite, and weight loss.

After more than one family member has been found to have stomach, breast, and colon cancer hereditary diffuse gastric cancer should be suspected in the following situations:

During a gastrectomy, the stomach will be removed, and then the first part of the small intestine will be connected with the esophagus.

CDH1 encodes the protein E-cadherin, which helps with cell to cell adhesion. A mutation causes an E-cadherin deficiency, and this deficiency causes the epithelial layers to lose their integrity which is a critical step in tumor progression. Loss of the E-cadherin protein allows the tumor cells to grow ad invade neighboring structures.

CDH1 is the only known gene that when changed causes gastric cancer that runs in the family, however, only 30-50% of individuals who have HDGC have an identifiable mutation in this gene.

A gastroenterologist will use an endoscope to go down through the esophagus into the stomach and take random biopsies of the stomach. Generally, multiple biopsies will be taken from 5 different sections of the stomach.

For hereditary diffuse gastric cancer, a variant means that the change in the DNA sequence of a gene has unknown effects on the gene function or the risk for disease. Individuals who have a variant identified are treated as if it were a negative result until it is reclassified.
Only 30-50% of individuals who undergo genetic testing will have a mutation identified in the CDH1 gene. This suggests that perhaps there is another gene, currently unknown, which may be causing hereditary diffuse gastric cancer.

A variant means that the change in the DNA sequence of a gene that has unknown effects on the gene function or the risk for disease. Individuals who have a variant identified are treated as if it were a negative result until it is reclassified.

Symptoms of stomach cancer are generally nonspecific at the early stages. Once symptoms do appear, individuals usually have an advanced stage of the disease. Symptoms in the late stage of gastric cancer may include: nausea, vomiting, abdominal pain, dysphagia (difficulty swallowing), feeling full quickly, loss of appetite, and weight loss.

The types of cancer that are suggestive of hereditary diffuse gastric cancer include: invasive lobular carcinomas, diffuse gastric cancer (also known as signet ring adenocarcinoma of the stomach), intra-mucosal signet ring cell adenocarcinomas of the stomach, and signet ring colon cancer.

Some individuals may develop cancer earlier or later than others within their family or between different families, which is known as a variable age of onset. Not everyone who has inherited a change will develop cancer and this is something known as incomplete penetrance.

Diffuse gastric cancer usually diagnosed under the age of 40, which is rare in the general population, and lobular breast cancer.

There is not newborn testing for hereditary diffuse gastric cancer in 2015.

There are different options for genetic testing and meeting with a genetics health provider can help determine which option of genetic testing makes the most sense for you based on your personal or family history. An individual may be only tested for the CDH1 gene. An individual may be tested for the CDH1 gene along with multiple other genes that can also cause an increased risk for stomach and/or breast cancer. Testing multiple genes at once is called a cancer panel.

In December of 2015, there is currently one clinical trial underway for HDGC. It involves a behavioral questionnaire to start a cancer registry for early onset and familial gastric cancer. The easiest place to look for more research on hereditary diffuse gastric cancer is to search for studies on the website: [link url="www.clinicaltrials.gov” target=”_blank”>www.clinicaltrials.gov.

There is no specific treatment to prevent diffuse gastric cancer syndrome. However, there are ways to manage and screen for gastric, breast, and colon cancer to try and prevent or discover cancer at an earlier stage.

Having hereditary diffuse gastric cancer is a predisposition for stomach, breast, and colon cancer. Having a mutation in the CDH1 gene does not guarantee someone will develop cancer.

If you have inherited a gene change that increases your risk for diffuse gastric cancer the chance you will actually get gastric cancer is up to 80% for males and females by age 80. The risk for lobular breast cancer is up to 60% for females by age 80, and the risk for colon cancer is increased above the general population risk.

Your doctor should also be aware of the signs and symptoms of stomach cancer including: nausea, vomiting, abdominal pain, dysphagia, feeling full quickly, loss of appetite, and weight loss.

Your doctor should be aware of the medical management guidelines found on NCCN.com which include:

There are a couple options when family planning. One option is to adopt or use a sperm or egg donor. Another option is to have biological children, and know that there is a 50% risk that each child could inherit this mutation. Another option is having preimplantation genetic diagnosis (PGD), which involves in vitro fertilization. Through the process of PGD, embryos can be checked to see if they contain the CDH1 mutation or not, and only embryos that do not contain the mutation will be implanted in the mother.

The gastrectomy procedures depends on your case and the surgical team. Your doctor can give you a better idea in your exact situation. The average procedure takes 4-5 hours and will require a 7-12 day stay in the hospital.

Hereditary diffuse gastric cancer is inherited in an autosomal dominant manner. This means, an individual only needs one mutation in order to have an increased risk for cancer. If a parent has a mutation there is a 50% chance that each of their children could inherit the mutation. If an individual has a mutation there is a 50% chance that their siblings also have the mutation.

You can start a support group by contacting already existing support groups and asking them how you they started their organization. It is also recommended that you contact a professional who can provide guidance. Also, look at: Global Genes’ Toolkits: https://globalgenes.org/toolkits/so-you-think-you-want-to-start-a-nonprofit/so-you-think-you-want-to-start-a-nonprofit-2/.

In addition to donating to your local cancer center, you can donate to research funds such as the “No Stomach For Cancer” fund ([link url="www.nostomachforcancer.org” target=”_blank”>www.nostomachforcancer.org) or or to Cancer Research UK ([link url="www.cancerreserachuk.org” target=”_blank”>www.cancerreserachuk.org).

Testing for diffuse gastric cancer can be done through a simple blood test. The type of tests to be ordered by your doctor is called sequencing of the CDH1 which is when the “spelling” of the CDH1 gene is checked for errors. They may also order a deletion/duplication analysis of the CDH1 gene that looks for big chunks of the gene that are missing or added that could be missed when sequencing. The tests are usually ordered by a genetics health provider after genetic counseling which will examine an individual’s personal and family history to determine if genetic testing for the CDH1 gene makes sense as opposed to testing for another genetic condition. A genetic counselor focused on cancer in your area can be found at [link url="www.nsgc.org” target=”_blank”>www.nsgc.org website.

The website: [link url="www.clinicaltrials.gov” target=”_blank”>www.clinicaltrials.gov gives a list of clinical trials currently underway for HDGC. You can also go to Center Watch Patient Notification Service, Clinical trials through the National Cancer Institute Search, and through the National Institutes of Health Service.

You can also find clinic research or scientific articles at: [link url="www.scholar.google.com” target=”_blank”>www.scholar.google.com and search "hereditary diffuse gastric cancer."

There are several cancer centers who work with individuals with gastric cancer. One example is Johns Hopkins’ Gastric Cancer Center which can be found at: http://www.hopkinsmedicine.org/gastric_cancer_center/treatments_services/hereditary_diffuse.html.

Some things can make hereditary diffuse gastric cancer worse. There are some risk factors that increase the risk for developing stomach cancer, however, having none or all of the risk factors does not guarantee you will or will not develop cancer.

The risk factors for stomach cancer include: ethnicity, geography, gender, age, H. Pylori infection, diet, obesity, tobacco, previous stomach surgery, and a family history.

Risk factors for breast cancer include: gender, age, family history, hormonal exposures (early menarche, late menopause, not having children, first live birth after 30, estrogen or hormone replacement therapy), radiation exposure, obesity, alcohol use, atypical hyperplasia or LCIS diagnosed by breast biopsy, and dense breast.

Genetic testing children under the age of 18 has always been controversial in genetic testing. However, since there have been reports of individuals under the age of 18 who have been diagnosed with hereditary diffuse gastric cancer, it has been suggested that genetic testing younger than 18 may be beneficial in some circumstances. The International Gastric Cancer Linkage Consortium agreed that genetic testing can begin at the age of 16 if there has been an early onset gastric cancer in the family.

There is no specific treatment to prevent diffuse gastric cancer syndrome. However, there are ways to manage and screen for gastric, breast, and colon cancer to try and prevent or discover cancer at an earlier stage. Hereditary diffuse gastric cancer screening recommendations include:

There are no other names for hereditary diffuse gastric cancer.

Support groups for hereditary diffuse gastric cancer include:

In 2015, doctors haven’t found that specific gene changes in CDH1 are related to specific types of gastric cancer. In other words, there are no genotype phenotype correlations with HDGC as of December 2015.

The differential diagnosis for HDGC includes: