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PubMed This is a summary of 79 peer-reviewed journal articles Updated
Medical Genetics

Starting Your Journey with HDGC: From Panic to Power

At a Glance

Hereditary Diffuse Gastric Cancer (HDGC) is a genetic syndrome caused by CDH1 or CTNNA1 mutations. While it increases the risk of stomach cancer, it is preventable. Management options include intensive endoscopic surveillance (Cambridge Protocol) or prophylactic stomach removal.

Finding out you have a CDH1 or CTNNA1 mutation can feel like a sudden, overwhelming storm. It is normal to feel fear, but this discovery is fundamentally a tool for empowerment. Before this result, you were at risk without a map; now, you have the information needed to prevent cancer before it ever starts [1][2].

Understanding Your Diagnosis

Hereditary Diffuse Gastric Cancer (HDGC) is a genetic syndrome that increases the risk of developing a specific type of stomach cancer called diffuse gastric cancer. Unlike common stomach cancers that form solid tumors, diffuse cancer spreads as individual cells (often called signet ring cells) within the stomach lining, making it very difficult to detect with standard tests [3][4].

  • CDH1 Mutation: This is the most common cause of HDGC. It affects the “glue” (E-cadherin) that holds cells together [5].
  • CTNNA1 Mutation: A rarer cause of HDGC that also affects cell adhesion. While it carries significant risks, it is often considered to have a slightly lower overall “penetrance” (likelihood of causing cancer) than CDH1 [6][7].

Stabilizing Facts

When you first search for HDGC, you may see frightening statistics from older studies. It is important to look at the most current data:

  1. Risks are being revised downward: Older studies suggested a 70–80% lifetime risk of stomach cancer. Current 2020 guidelines and recent studies show that for many people—especially those whose mutations were found “incidentally” through broad genetic panels—the risk is often much lower, estimated between 25% and 42% [8][9][1].
  2. Prevention is highly effective: For those at high risk, a prophylactic total gastrectomy (PTG) — the surgical removal of the stomach before cancer develops — is considered a “standard of care” because it essentially eliminates the risk of stomach cancer [10][11].
  3. Surveillance is an option: If you are not ready for surgery, expert centers can perform intensive endoscopic surveillance (using the Cambridge Protocol). This involves high-definition internal exams with numerous “mapping” biopsies to monitor the stomach lining [1][12][13].

Understanding Your Specific Risk

Your risk level is influenced by your family history and how your mutation was discovered.

Mutation/Group Estimated Stomach Cancer Risk (by age 80) Estimated Lobular Breast Cancer Risk (Women)
CDH1 (Classic Family History) ~60% - 70% [14] ~37% - 55% [8]
CDH1 (Incidental Discovery) ~25% - 42% [8][9] ~37% [9]
CTNNA1 ~49% - 57% [6] Significantly lower than CDH1 [6]

Note: For women with a CDH1 mutation, the risk of lobular breast cancer (a specific type of breast cancer) is also increased. Management typically involves breast MRIs rather than immediate surgery [2][1].

Moving Forward

You do not have to make decisions today. The 2020 International Gastric Cancer Linkage Consortium (IGCLC) guidelines emphasize individualized care [1]. Your next steps should involve a multidisciplinary team.

Explore the rest of this guide to learn more:

01

The Biology of HDGC: Why the "Glue" Matters

Learn the biology behind Hereditary Diffuse Gastric Cancer (HDGC). Understand how CDH1 and CTNNA1 mutations cause signet ring cells and diffuse stomach cancer.

02

Monitoring Your Health: Surveillance and the Cambridge Protocol

Learn about HDGC surveillance and the Cambridge Protocol. Understand why 30+ biopsies are needed, endoscopy limits, and breast and colon cancer screening.

03

The Decision: Surgery and Your "New Normal"

Learn about prophylactic total gastrectomy (PTG) for CDH1 and HDGC. Compare stomach removal surgery with intensive surveillance to make the right choice.

04

Life Without a Stomach: Nutrition and Survivorship

Learn how to manage life without a stomach after a total gastrectomy. Understand dumping syndrome, vitamin B12 needs, diet changes, and weight stabilization.

05

Building Your Care Team: Why Experts Matter

Learn how to build an expert care team for Hereditary Diffuse Gastric Cancer (HDGC). Discover why high-volume centers matter and which specialists you need.

Finding this mutation is not a diagnosis of cancer; it is a diagnosis of an opportunity to prevent it.

Common questions in this guide

What does a CDH1 or CTNNA1 mutation mean for my health?
These mutations affect the cellular 'glue' that holds cells together, which increases your risk for a specific type of stomach cancer called diffuse gastric cancer. Women with a CDH1 mutation also have a higher risk of developing lobular breast cancer.
Is stomach cancer inevitable if I have a CDH1 mutation?
No, cancer is not inevitable. While older statistics suggested a very high lifetime risk, recent studies show the actual risk may be much lower. For people whose mutations were found incidentally, the lifetime risk of stomach cancer is currently estimated between 25% and 42%.
How can I prevent stomach cancer if I have HDGC?
The most effective prevention is a prophylactic total gastrectomy, which involves surgically removing the stomach before cancer can develop. If you are not ready for surgery, intensive endoscopic surveillance is another option to carefully monitor your stomach lining over time.
What is the Cambridge Protocol for HDGC?
The Cambridge Protocol is a specialized, highly detailed endoscopic surveillance method used for monitoring people with HDGC. It involves using high-definition cameras and taking numerous mapping biopsies across the stomach lining to check for microscopic, early signs of cancer.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Does our family meet the 'classic' IGCLC criteria for HDGC, and how does that affect my specific risk estimate?
  2. 2.Was my mutation found incidentally, and do you follow the 2020 IGCLC guidelines for 'incidental' carriers?
  3. 3.If I choose surveillance over surgery for now, do you use the 'Cambridge Protocol' for endoscopies?
  4. 4.How many prophylactic total gastrectomies does this hospital perform annually for CDH1/CTNNA1 carriers?
  5. 5.Can you refer me to a specialized dietitian and a genetic counselor who focuses on hereditary cancer syndromes?

Questions For You

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References

References (14)
  1. 1

    Hereditary diffuse gastric cancer: updated clinical practice guidelines.

    Blair VR, McLeod M, Carneiro F, et al.

    The Lancet. Oncology 2020; (21(8)):e386-e397 doi:10.1016/S1470-2045(20)30219-9.

    PMID: 32758476
  2. 2

    Hereditary Diffuse Gastric Cancer Syndrome and the Role of CDH1: A Review.

    Gamble LA, Heller T, Davis JL

    JAMA surgery 2021; (156(4)):387-392 doi:10.1001/jamasurg.2020.6155.

    PMID: 33404644
  3. 3

    Outcomes after prophylactic gastrectomy for hereditary diffuse gastric cancer.

    van der Kaaij RT, van Kessel JP, van Dieren JM, et al.

    The British journal of surgery 2018; (105(2)):e176-e182 doi:10.1002/bjs.10754.

    PMID: 29341148
  4. 4

    Inherited CDH1 pathogenic variant: is there a place for surveillance of esophageal gastric inlet patch?

    Leclercq P, Jadot V, Bours V, et al.

    Therapeutic advances in gastroenterology 2020; (13()):1756284820916399 doi:10.1177/1756284820916399.

    PMID: 32523621
  5. 5

    Prognosis and outcome in CDH1-mutant lobular breast cancer.

    Corso G, Veronesi P, Sacchini V, Galimberti V

    European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) 2018; (27(3)):237-238 doi:10.1097/CEJ.0000000000000405.

    PMID: 29595757
  6. 6

    Hereditary diffuse gastric cancer spectrum associated with germline CTNNA1 loss of function revealed by clinical and molecular data from 351 carrier families and over 37 000 non-carrier controls.

    Lobo S, Dias A, Pedro AM, et al.

    Gut 2026; (75(5)):872-885 doi:10.1136/gutjnl-2024-334601.

    PMID: 40998418
  7. 7

    Cancer predisposition and germline CTNNA1 variants.

    Lobo S, Benusiglio PR, Coulet F, et al.

    European journal of medical genetics 2021; (64(10)):104316 doi:10.1016/j.ejmg.2021.104316.

    PMID: 34425242
  8. 8

    Comparison of CDH1 Penetrance Estimates in Clinically Ascertained Families vs Families Ascertained for Multiple Gastric Cancers.

    Roberts ME, Ranola JMO, Marshall ML, et al.

    JAMA oncology 2019; (5(9)):1325-1331 doi:10.1001/jamaoncol.2019.1208.

    PMID: 31246251
  9. 9

    Germline CDH1 Variants and Lifetime Cancer Risk.

    Ryan CE, Fasaye GA, Gallanis AF, et al.

    JAMA 2024; (332(9)):722-729 doi:10.1001/jama.2024.10852.

    PMID: 38873722
  10. 10

    Panel testing reveals nonsense and missense CDH1 mutations in families without hereditary diffuse gastric cancer.

    Huynh JM, Laukaitis CM

    Molecular genetics & genomic medicine 2016; (4(2)):232-6 doi:10.1002/mgg3.197.

    PMID: 27064202
  11. 11

    Pioneering use of genetic analysis for CDH1 to identify candidates for prophylactic total gastrectomy to prevent hereditary diffuse gastric cancer.

    Mokhtari-Esbuie F, Szeglin B, Ravari MR, et al.

    eGastroenterology 2023; (1(2)) doi:10.1136/egastro-2023-100017.

    PMID: 38188186
  12. 12

    Endoscopic surveillance with systematic random biopsy for the early diagnosis of hereditary diffuse gastric cancer: a prospective 16-year longitudinal cohort study.

    Lee CYC, Olivier A, Honing J, et al.

    The Lancet. Oncology 2023; (24(1)):107-116 doi:10.1016/S1470-2045(22)00700-8.

    PMID: 36509094
  13. 13

    Laparoscopic Prophylactic Total Gastrectomy for Hereditary Diffuse Gastric Cancer in CDH1 Mutation Carriers.

    Ithurralde-Argerich J, Rosner L, Rizzolo M, et al.

    Journal of laparoendoscopic & advanced surgical techniques. Part A 2021; (31(7)):729-737 doi:10.1089/lap.2021.0239.

    PMID: 34097461
  14. 14

    Endoscopic Ultrasound Has Limited Utility in Diagnosis of Gastric Cancer in Carriers of CDH1 Mutations.

    Kumar S, Katona BW, Long JM, et al.

    Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 2020; (18(2)):505-508.e1 doi:10.1016/j.cgh.2019.04.064.

    PMID: 31077828

This page provides educational information about Hereditary Diffuse Gastric Cancer (HDGC) and genetic risk. It does not replace professional medical advice from a qualified genetic counselor or oncologist regarding your specific mutation.

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