Medical Oncologist
Genetic risk & family screening
Hereditary Diffuse Gastric Cancer — and the CDH1 Gene
A fault in the CDH1 gene raises the lifetime risk of diffuse stomach cancer substantially. If you or a family member has received a CDH1 diagnosis, or if your family has had several cases of diffuse gastric cancer, this page explains what the numbers mean and what happens next.
Medically reviewed by Dr. C. Raghavendra Reddy, Medical Oncologist, MBBS (Gold Medal) · DNB · DM (Medical Oncology, Gold Medal) · Last reviewed August 2026
- High lifetime risk — IGCLC data puts cumulative gastric cancer risk at around 70 percent in male carriers and 56 percent in female carriers by age 80.
- Women face a second risk — Female CDH1 carriers also have an approximately 42 percent lifetime risk of lobular breast cancer, according to IGCLC.
- Surveillance starts early — Annual endoscopy using the Cambridge Protocol is recommended from around age 18 to 20.
- Gastrectomy is a choice, not an emergency — Prophylactic removal of the stomach eliminates the gastric cancer risk but is a significant surgery discussed over time with your team.
17+
Cancer Specialists
on Panel
on Panel
96.9%
Breast Cancer
Survival Rate*
Survival Rate*
15,000+
Patients
Treated
Treated
4.8★
Google Rating
(800+ reviews)
(800+ reviews)
A CDH1 gene mutation causes Hereditary Diffuse Gastric Cancer syndrome. Based on IGCLC data, lifetime gastric cancer risk reaches around 70 percent in men and 56 percent in women who carry a pathogenic CDH1 variant. Women also face an approximately 42 percent lifetime risk of lobular breast cancer. Annual surveillance and genetic counselling are advised from around age 18.
What does a CDH1 mutation actually mean for your health?
The CDH1 gene makes a protein called E-cadherin, which acts like a biological glue holding stomach cells in their correct position. When a pathogenic variant in CDH1 is inherited, that protein is faulty, and diffuse-type stomach cancer becomes much more likely over a lifetime.
This is not a risk you can see or feel. Diffuse gastric cancer does not form a visible lump — it spreads through the stomach wall in microscopic sheets of signet ring cells, which is why ordinary symptoms appear late and why surveillance must begin long before any symptom develops.
The IGCLC, the body that sets international guidance for this condition, places cumulative gastric cancer risk by age 80 at around 70 percent for male carriers and 56 percent for female carriers. Female carriers also carry an approximately 42 percent cumulative risk of lobular breast cancer by age 80. These are absolute lifetime figures, not relative comparisons to the general population.
What is the recommended screening schedule, age by age?
From age 18 to 20 — begin annual endoscopy
IGCLC recommends starting upper GI endoscopy from around age 18 to 20, or five years before the youngest diagnosis in your family, whichever comes first. Each endoscopy follows the Cambridge Protocol — random biopsies taken from multiple defined regions of the stomach lining rather than a visual-only inspection.
Annually — continue surveillance endoscopy
Endoscopy continues once a year for as long as you have your stomach. Even with the Cambridge Protocol, diffuse lesions can be missed, so annual commitment matters. Your team will review whether any findings change the timeline for the surgical conversation.
From age 30 (women) — add annual breast MRI
Female CDH1 carriers are advised to begin annual breast MRI from around age 30. MRI detects lobular breast cancer more reliably than mammography alone at this age, because lobular cancer does not always form a dense mass visible on X-ray.
From age 35 (women) — add annual mammography alongside MRI
Annual mammography is added from around age 35, used alongside breast MRI. The two investigations detect different features, and IGCLC guidance supports using both for comprehensive breast surveillance in female carriers.
Ages 18–40 — discuss prophylactic gastrectomy timing
Prophylactic total gastrectomy — removal of the stomach before cancer develops — eliminates the gastric cancer risk. Most carriers discuss timing with their oncologist and surgeon between the ages of 18 and 40, after full counselling on the nutritional and lifestyle implications. The decision is individual and not automatic.
Meet the Specialists
17+ senior cancer specialists. One panel for your case.
Trained at AIIMS, Tata Memorial, and leading international centres. Combined 150+ years of experience. Every complex case is reviewed by 3+ of them — together.
Medical Oncologist
Dr. C. Raghavendra Reddy
MBBS(Gold Medal), DNB(General Medicine), DM(Medical Oncology)(Gold Medal)
Medical Oncologist
Dr. Bharati Devi Gorantla
MBBS, MD(General Medicine), DM(Medical Oncology)(Adyar,Chennai), ECMO, MRCP SCE(UK)
Medical Oncologist
Dr. Owais Mohammed
MBBS, MD (General Medicine), DrNB (Medical Oncology), ECMO, MRCP SCE (Medical Oncology) (UK)
Medical Oncologist
Medical Oncologist
Surgical Oncologist
Dr. Muralidhar Muddusetty
MBBS (AIIMS), MS (Surgery) (AIIMS), DNB (Surgical Oncology), MRCS (Edinburgh)
Surgical Oncologist
Surgical Oncologist
Surgical Oncologist
Dr. Vinay Mamidala
MBBS, MS(General Surgery), M.Ch(Surgical Oncology), FMAS, FARIS(Ongoing)
Surgical Oncologist
Radiation Oncologist
Radiation Oncologist
Radiation Oncologist
Hematologist
Interventional Radiologist
Dr. Mohammed Imran
Surgical Oncologist
Dr. Vajja Sandeep Kumar
MBBS, MS (General Surgery), DrNB (Surgical Oncology), FALS Oncology
Surgical Oncologist
Want a specific doctor for your case? Mention them when booking.
Book Free ConsultationBook an appointment with our specialist
Share your name and number — we'll call you back within 30 minutes to schedule your consultation.
Get a straight answer from a specialist
45 minutes, your reports reviewed, your questions answered in plain language.
What does my geneticist mean by CDH1, pathogenic variant and HDGC?
- CDH1 gene
- The gene that provides instructions for making E-cadherin, a protein that keeps stomach-lining cells attached and organised. A pathogenic variant in CDH1 disrupts this function and raises the risk of diffuse gastric cancer.
- Pathogenic variant
- A confirmed DNA change that is known to cause disease — not a harmless spelling variation. Genetic testing distinguishes pathogenic variants from variants of uncertain significance, which require further evidence before a management decision can be made.
- Hereditary Diffuse Gastric Cancer (HDGC)
- The inherited syndrome caused by pathogenic CDH1 variants. It substantially raises the lifetime risk of diffuse gastric cancer and, in women, lobular breast cancer. It follows an autosomal dominant pattern — one altered copy of the gene is enough to carry the risk.
- Diffuse gastric cancer
- A type of stomach cancer where malignant cells spread through the stomach wall without forming a discrete mass. It looks and behaves very differently from intestinal-type gastric cancer and rarely causes symptoms until it is advanced.
- Signet ring cells
- The characteristic cell type in diffuse gastric cancer, named for their appearance under a microscope. Their presence in biopsies from a CDH1 carrier confirms early cancer and guides the urgency of next steps.
- Prophylactic total gastrectomy
- Surgical removal of the entire stomach before cancer develops. It eliminates the gastric cancer risk for CDH1 carriers. It is a major, irreversible procedure with permanent implications for how you eat, and the decision requires thorough counselling.
- Lobular breast cancer
- A form of breast cancer arising in the milk-producing glands. It is less likely than ductal cancer to form a palpable lump and may not appear on mammography alone. It is the second primary cancer risk for female CDH1 carriers.
Who should consider CDH1 testing?
IGCLC criteria for offering CDH1 testing include: two or more family members with diffuse gastric cancer, particularly where one was diagnosed before age 50; a single case of diffuse gastric cancer diagnosed before age 45; a personal or family history of both diffuse gastric cancer and lobular breast cancer; and any family with a known CDH1 mutation.
Testing is done from a blood sample and looks for pathogenic variants across the CDH1 gene. Results are interpreted by a clinical geneticist alongside your family history, not in isolation. If your result comes back as a variant of uncertain significance rather than a confirmed pathogenic variant, your team will explain what surveillance is still appropriate while more evidence is gathered.
A negative CDH1 result in a family with a strong HDGC history does not always mean no risk. In some families no mutation is found yet the pattern still meets surveillance criteria — a situation called mutation-negative HDGC. Your geneticist will advise whether ongoing endoscopy remains appropriate regardless of the result.
What are your options after a confirmed CDH1 mutation?
You have two main paths for managing gastric cancer risk: surveillance endoscopy or prophylactic total gastrectomy. Many carriers begin with surveillance while they consider the surgical option over time — these are not mutually exclusive.
Surveillance endoscopy, even with the Cambridge Protocol, has real limitations. Diffuse lesions are tiny and scattered, and biopsies from any one visit may not capture all of them. Annual endoscopy reduces the chance of missing a developing cancer, but it does not eliminate that risk the way surgery does.
Prophylactic gastrectomy removes the risk entirely, but it changes how you eat for life. You will eat smaller, more frequent meals. Some nutritional deficiencies — particularly vitamin B12, iron and calcium — require lifelong supplementation. Most people adapt well over one to two years, but the adjustment is real and needs preparation.
For women, breast surveillance is a third strand of the plan and runs alongside whatever gastric management you choose. Discuss the full picture with your oncologist, clinical geneticist and a surgeon experienced in this condition before deciding.
Explore 113 more Family, Fertility, Diet & Emotional Wellbeing topics
Genetic Predisposition & Family Risk
- BRCA Testing in India: Cost, Process and Where to Get It Done
- Cascade Testing: Getting Your Family Members Tested
- Coping With the Anxiety of a Positive Genetic Test
- Does a BRCA Mutation Mean You Will Definitely Get Cancer?
- Family History of Cancer: Should You Get Genetic Testing?
- Genetic Counselling: What Actually Happens in the Session
- Hereditary Diffuse Gastric Cancer and the CDH1 Gene
- How to Tell Your Children and Siblings About a Genetic Risk
- I'm BRCA Positive but Have No Cancer: What Happens Now?
- IVF and Preimplantation Testing to Avoid Passing On a Mutation
- Li-Fraumeni Syndrome: Living With a TP53 Mutation
- Lynch Syndrome: Cancers, Screening and Treatment Implications
- MEN2, VHL and Other Endocrine Cancer Syndromes
- MUTYH, PALB2, ATM and CHEK2: Moderate-Risk Genes Explained
- Male BRCA Carriers: The Risks Nobody Talks About
- PARP Inhibitors: How a Genetic Mutation Becomes a Treatment Advantage
- Risk-Reducing Mastectomy: How to Decide
- Risk-Reducing Ovary and Tube Removal: Timing and Consequences
- Somatic Mutation Found on NGS: Could It Be Inherited?
- Surveillance Instead of Surgery: What Screening Looks Like
- Which Family Histories Actually Suggest a Hereditary Cancer Syndrome?
- Will a Genetic Test Result Affect Your Insurance in India?
Caregiver Enablement
- Building a Care Roster When One Person Can't Do It All
- Caregiver Burnout: Recognising It Before It Breaks You
- Caregiver Red Flag Chart: When to Take Them to Hospital
- Caring for an Elderly Parent on Oral Cancer Tablets
- Cooking for Someone on Targeted Therapy: A Kitchen Guide
- Coordinating Care From Abroad: A Guide for NRI Families
- Financial Management for Caregivers: Bills, Claims and Records
- How to Get a Second Opinion Without Offending Your Doctor
- How to Track Side Effects: A Simple Daily Diary System
- Managing Medicines, Refills and Pharmacy Runs
- Questions Every Caregiver Should Ask at the Oncology Visit
- Supporting Someone Emotionally Without Saying the Wrong Thing
- The Complete Caregiver's Guide to Targeted Therapy
- What to Do When the Patient Refuses to Take Their Medicine
Diet, Nutrition & Complementary Therapy
- Ayurveda Alongside Targeted Therapy: An Honest Assessment
- Do Immunity Boosters Help During Cancer Treatment?
- Does Sugar Feed Cancer? Separating Myth From Fact
- Eating With Mouth Sores: Foods That Don't Hurt
- Eating to Control High Blood Sugar From Cancer Drugs
- Food Safety and Hygiene for Cancer Patients at Home
- Foods to Avoid on Targeted Therapy
- How Much Protein Does a Cancer Patient Actually Need?
- Hydration: How Much Water and What Counts
- Is Cow's Milk, Soya or Non-Veg Food Safe During Cancer Treatment?
- Keto and Intermittent Fasting During Cancer Treatment: Is It Safe?
- Managing Weight Loss and Muscle Wasting
- What Should You Eat While on Targeted Therapy? A Practical Indian Diet Guide
- What to Eat When You Have Diarrhoea From Cancer Tablets
- Yoga and Pranayama During Cancer Treatment
Fertility, Pregnancy & Sexual Health
- Accidental Pregnancy While on Targeted Therapy: What Now?
- Can You Breastfeed While on Targeted Therapy?
- Cancer Diagnosed During Pregnancy: Can Targeted Therapy Be Used?
- Contraception on Targeted Therapy: Which Methods Are Safe?
- Early Menopause Caused by Cancer Treatment
- Erectile Dysfunction and Sexual Changes in Men on Treatment
- Fertility After Long-Term Targeted Therapy: What the Data Shows
- Fertility Preservation Before Starting Treatment: Your Options and Timeline
- How Long Must You Wait Before Trying to Conceive?
- Sperm Banking Before Cancer Treatment: A Practical Guide
- Talking to Your Partner About Sex During Cancer Treatment
- Vaginal Dryness, Pain and Low Libido During Treatment
- Will Targeted Therapy Affect My Fertility?
Mental Health & Emotional Wellbeing
- Body Image When Your Skin, Nails and Hair Change
- Cancer Support Groups in India: How to Find One
- Depression During Long-Term Cancer Treatment
- Handling Unhelpful Advice and Toxic Positivity
- Living With Cancer as a Chronic Disease: A New Identity
- Sleep, Anxiety and Night-Time Fear During Treatment
- Talking to Your Children About Your Cancer Diagnosis
- Telling Friends, Relatives and Neighbours: How Much to Share
- The Fear That the Drug Will Stop Working: How to Live With It
- When Should You See a Psycho-Oncologist?
Myths, Misinformation & Verification
- Are Generic Cancer Drugs Fake or Weaker?
- Can Cancer Be Cured Without Any Modern Medicine?
- Cannabis and CBD Oil for Cancer: What the Evidence Actually Says
- Does Soursop, Apricot Seed or Alkaline Water Cure Cancer?
- Does a Biopsy Spread Cancer?
- How to Fact-Check Cancer Information You Read Online or From AI
- Miracle Cancer Cures on WhatsApp and YouTube: How to Spot a Fake
- Myth: Cancer Treatment Is Worse Than the Disease
- Myth: If the Scan Is Clear You Can Stop the Tablets
- Myth: Positive Thinking Cures Cancer
- Myth: Sugar, Milk or Non-Veg Food Feeds Cancer
- Myth: Targeted Therapy Has No Side Effects
- Myth: Targeted Therapy Is Only for the Rich
Palliative Care & End of Life
- Breathlessness and Comfort Care in Advanced Cancer
- Hospice and Home Palliative Care Services in India
- How to Have a Goals-of-Care Conversation With Your Doctor
- Pain Control at Home: What's Possible and What to Ask For
- Palliative Care Is Not Giving Up: Clearing the Biggest Myth
- Should You Ask How Long You Have Left?
- Supporting a Family Member in Their Last Months
- What 'Best Supportive Care' Actually Means
- When Is It Right to Stop Cancer Treatment?
Special Populations & Comorbidities
- Cancer Treatment After an Organ Transplant
- Cancer Treatment for Patients on Dialysis
- Cancer Treatment in Patients With Past or Active Tuberculosis
- Growth, Puberty and School During Childhood Cancer Treatment
- Hepatitis B and C Reactivation Risk During Cancer Treatment
- Managing Diabetes While on Targeted Therapy
- Obesity, Underweight and Dosing: Does Body Size Change the Dose?
- Paediatric Targeted Therapy: What Parents Need to Know
- Targeted Therapy With Autoimmune Disease
- Targeted Therapy With Chronic Kidney Disease
- Targeted Therapy With Existing Heart Disease
- Targeted Therapy With Liver Disease or Cirrhosis
- Targeted Therapy for Adolescents and Young Adults
- Targeted Therapy for Patients With Mental Illness or Dementia
- Targeted Therapy in HIV-Positive Patients
- Targeted Therapy in Patients Over 75: Is It Worth It?
- Treating Patients With Poor Performance Status
Next step
Still not sure what applies to you?
Send your reports across and a senior medical oncologist will go through what they mean, what is known, and what the options actually are.
Common questions
Frequently asked questions
Does a CDH1 mutation mean I will definitely get stomach cancer?
No. Carrying a pathogenic CDH1 variant means your lifetime risk is substantially elevated — IGCLC data puts it at around 70 percent for men and 56 percent for women by age 80 — but not every carrier develops cancer, and the risk can be managed through surveillance or surgery. What you should not do is assume you will be among those who remain unaffected and delay entering a surveillance programme. The earlier your team is involved, the more options remain open to you.
How is CDH1 genetic testing done?
A blood sample is taken and sent to a laboratory that analyses the CDH1 gene for pathogenic changes. Results usually take several weeks. The report will describe the finding as pathogenic, likely pathogenic, variant of uncertain significance, or negative. A clinical geneticist will explain what your specific result means for your surveillance plan and for family members who may also wish to be tested.
Can I pass this mutation to my children?
Yes. CDH1 mutations follow an autosomal dominant inheritance pattern, meaning each child of a carrier has a one-in-two chance of inheriting the variant. Testing can be offered to children when they are old enough to make an informed decision — typically around age 18, in time to begin surveillance before the recommended window opens. Genetic counselling helps families work through both the decision to test children and how to share results with other relatives.
How reliable is endoscopy for catching early cancer in CDH1 carriers?
It is the best currently available non-surgical tool, but it has significant limitations. Diffuse gastric cancer begins as microscopic signet ring cell foci scattered across the stomach lining and invisible to the naked eye. The Cambridge Protocol tries to compensate by taking a large number of random biopsies from defined regions, but even this approach can miss lesions between annual visits. This is why the conversation about prophylactic gastrectomy is a genuine clinical option rather than a last resort.
What is life like after prophylactic gastrectomy?
Most people live well after a total gastrectomy, but the adjustment takes time. Without a stomach, food passes directly from the oesophagus to the small intestine. You will need to eat small amounts frequently, eat slowly and chew thoroughly. Dumping syndrome — feeling unwell after eating, particularly sugary or rich foods — is common in the early months and usually improves. You will need lifelong B12 injections, iron monitoring, and calcium and vitamin D supplementation. A dietitian experienced in post-gastrectomy care is an essential part of the team, not an optional extra.
My relative had stomach cancer but no genetic test was ever done. Where do I start?
Start by asking your doctor for a referral to a clinical geneticist or a hereditary cancer risk clinic. Bring as much family history as you can: the type of stomach cancer, the age at diagnosis, and any other cancers in first- or second-degree relatives. If the relative who had cancer is still alive, testing them first gives the clearest result — a confirmed pathogenic variant in a blood relative makes your own test much simpler to interpret. If they have passed away, a geneticist can still work through the family history to decide whether testing you directly is warranted.