What Is Hereditary Diffuse Gastric Cancer?

  • Titilayo Ologun Master's degree, Bioinformatics, Teesside University, UK
  • Arunima Babu  Masters, Biomedical Sciences, University of Aberdeen, UK
  • Katheeja Imani MRes Biochemistry, University of Nottingham, UK

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Hereditary diffuse gastric cancer (HDGC) is an uncommon genetic disorder linked to a higher chance of developing gastric (stomach) cancer. Diffuse gastric cancer is sometimes referred to as "signet ring cell gastric cancer" as stomach lining cells develop into signet-ring-shaped cells because of HDGC. The term "diffuse'' is used because this cancer frequently spreads to other parts of the stomach, either expanding alone or in tiny groups as opposed to staying in one spot. A small percentage of diffuse gastric cancers, which make up around 20% of all stomach cancers, are brought on by HDGC.

This form of stomach cancer is inherited; parents may pass it on to their offspring. Additionally, having HDGC raises your chance of developing other cancers, such as breast cancer. Stomach cancer can develop at any age. However, the average age at which someone with HDGC is identified with the disease is 38. The average age of persons who get gastric cancer that is not related to this disease is above 60. Gastric cancer is the fifth most frequent malignancy globally and the third biggest cause of cancer death in people after lung cancer and colorectal cancer.1

The precise number of HDGC patients is unknown. Varied ethnic groups have varied rates of HDGC. Only 1% to 3% of all stomach cancer cases are HDGC.HDGC is mostly diagnosed before 40.

The CDH1 gene is where most HDGC mutations originate.3 Genetic testing can be done on people who have relatives who have HDGC to see whether they have the CDH1 gene mutation or any other less common mutations that are known to cause HDGC. If you have two or more members of your immediate family who have been diagnosed with diffuse gastric cancer or who were diagnosed when they were young, you should consider genetic counselling. 

Since HDGC does not exhibit any distinctive symptoms or outward indicators that set it apart from other types of gastric cancer, the diagnosis might be difficult. However, if there are many lobular breast cancer instances or diffuse gastric cancer in the family, it may cause HDGC to be suspected.1

Causes of HDGC

There is a 50% likelihood that the children of parents who have the HDGC-causing CDH1 gene mutation (alteration) will also have the mutation passed down through generations. Worldwide, there are regional variations in the incidence of stomach cancer. Only a small portion of stomach cancer cases in the US are thought to be caused by HDGC, which affects fewer than 1% of the population. The countries of Central and South America, as well as Japan, China, and other Southeast Asian nations, have the highest incidence of stomach cancer worldwide.

Signs and symptoms of HDGC

Early gastric cancer symptoms frequently resemble those of mild illnesses, indigestions, and stomach aches. They are typically hazy and nonspecific. However, as the illness advances, the symptoms worsen and remain longer. 

Some of the most typical signs of stomach cancer include the following:

  • Discomfort or pain in the abdomen
  • Dark or bloody stools
  • Constant tiredness
  • Having trouble swallowing
  • Feeling full or bloated even after a small meal
  • Acid reflux and indigestion
  • Reduced appetite
  • Nausea and vomiting
  • Unintentional loss of weight 

Diagnosis of HDGC

Given that several of the more popular imaging techniques used to look for stomach cancer cannot detect HDGC, HDGC can be challenging to diagnose. As a result, HDGC is discovered after the disease has progressed further to a later stage. 

Imaging studies and biopsies could be used to identify HDGC that has progressed to other parts of the body.

  • Imaging: Your physician will utilize imaging studies such as an ultrasound, CT, or PET scan to determine the location and size of the tumour if you have any symptoms of HDGC. The presence of tumour metastasis to other regions in the body will also be checked. 
  • Biopsies: The doctor will perform one or more biopsies to get a tiny sample of the tumour’s tissue to establish whether it is HDGC. To determine the type of tumour present in the sample, a specialist called a pathologist will examine cells under a microscope.

Management and treatment for HDGC

Every patient will receive individualized care. To determine the best course of action for your tumour, consult with an HDGC therapy specialist.          

Common treatment and management plans for HDGC include:

  • Surgery: the entire stomach is typically removed during surgery to lower the chance of the cancer developing again or spreading
  • Chemotherapy: This is used to treat HDGC when surgery is not an option or when the disease has spread 
  • Radiotherapy: high-energy photon or X-ray beams are used in radiation treatment to either kill or slow the growth of cancer cells
  • Immunotherapy: In immunotherapy, cancer cells are attacked and eliminated by the body's own immune system
  • Targeted drug therapy: One well-known type of targeted medication treatment frequently utilized with gastric cancer is monoclonal antibodies. Chemotherapy is frequently used in conjunction with this kind of treatment.


How can I prevent HDGC?

Individuals assigned female at birth (AFABs) who are at high risk for HDGC should talk to their doctors about breast cancer screening options when they are 30 years old. The most effective method of screening for breast cancer in AFABs who have a CDH1 mutation is not entirely known.

Options for screening include:

  • Self-exams of the breast once a month
  • Every six months, a doctor or nurse should undertake clinical breast exams
  • Routine breast imaging using mammograms, ultrasounds, and/or breast MRI 

How common is HDGC?

The precise number of HDGC patients is unknown. Varied ethnic groups have varied rates of HDGC. 1% to 3% of stomach cancers are caused by HDGC. The majority of HDGC patients are diagnosed before 40.

Who is at risk from HDGC?

Not every person with an HDGC gene mutation will develop cancer. By the age of 80, those assigned male at birth (AMABs) are anticipated to have a lifetime risk of diffuse gastric cancer of 67% to 70%, while AFABs are anticipated to have a lifetime risk of 56% to 83%. An AFAB with a CDH1 gene mutation has a 39%–52% probability of developing lobular breast cancer by the age of 80.

A person is at risk of HDGC in any of the situations listed below:

  • Families with at least 1 occurrence of diffuse gastric cancer and 2 or more cases of stomach cancer
  • Under 40 years of age with a diffuse gastric cancer diagnosis
  • Family history of lobular breast cancer and diffuse gastric cancer, with at least one diagnosis occurring before age 50
  • Two or more lobular breast cancer cases diagnosed before 50 in a family
  • An individual who has been diagnosed with lobular breast cancer more than once before the age of 50
  • Having a cleft lip or palate personally or via family history is a risk factor for diffuse gastric cancer

When should I see a doctor?

It is advised that individuals who have been identified as carriers of this genetic mutation or if any of the close family members were diagnosed before the age of 50 with lobular breast cancer or diffuse gastric cancer should talk to their healthcare provider about the best preventative measures for cancer. 


Hereditary Diffuse Gastric Cancer (HDGC) is a rare genetic disorder associated with an increased risk of stomach cancer, specifically the diffuse type. HDGC is characterized by a mutation in the CDH1 gene, inherited from parents, elevating the likelihood of passing it to their children. The condition often remains asymptomatic, making diagnosis challenging, but a family history of diffuse gastric or lobular breast cancer may raise suspicion. HDGC diagnosis involves genetic testing in some cases due to the limitations of imaging techniques. Treatment options include individualized plans, with surgery, chemotherapy, radiotherapy, immunotherapy, and targeted drug therapy among the common approaches. Prevention strategies involve breast cancer screening for those who have a family history of diffuse gastric or lobular breast cancer. The disease predominantly affects those under 40, with regional variations in its incidence globally. Understanding HDGC and its risk factors is crucial for early detection and tailored management. Talk to your healthcare provider if there is a family history. 


  1. Luo W, Fedda F, Lynch P, Tan D. CDH1 Gene and Hereditary Diffuse Gastric Cancer Syndrome: Molecular and Histological Alterations and Implications for Diagnosis And Treatment. Front Pharmacol [Internet]. 2018 [cited 2023 Jun 20];9. Available from: https://www.frontiersin.org/articles/10.3389/fphar.2018.01421 

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This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.

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Titilayo Ologun

Master's degree, Bioinformatics, Teesside University

Titilayo is a versatile professional excelling as a Biochemist, Public Health Analyst, and Bioinformatician, driving innovation at the intersection of Science and Health. Her robust foundation encompasses profound expertise in scientific research methodologies, literature reviews, data analysis, interpretation, and the skill to communicate intricate scientific insights. Driven by an ardent commitment to data-driven research and policy advancement, she remains resolute in her mission to elevate healthcare standards through her interdisciplinary proficiency and unwavering pursuit of distinction. With a passion for knowledge-sharing, she brings a unique perspective to each piece.

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