What are the guidelines for screening with Esophagogastroduodenoscopy (EGD) in individuals with a family history of stomach cancer?

EGD Screening Guidelines for Family History of Gastric Cancer

For individuals with a first-degree relative with gastric cancer and a normal initial EGD, screening EGD should be considered every 3-5 years, with the decision based on the presence of additional risk factors such as H. pylori infection status and ethnicity. 1

Risk Stratification by Family History Type

The approach to screening differs substantially based on the specific hereditary syndrome versus sporadic familial clustering:

Hereditary Diffuse Gastric Cancer (HDGC)

• Genetic testing for CDH1 mutations is recommended in families meeting International Gastric Cancer Linkage Consortium (IGCLC) criteria 1
• For confirmed CDH1 mutation carriers:
  • Annual endoscopy surveillance with a minimum of 30 random biopsies is recommended for those under age 20 or declining gastrectomy 1
  • Prophylactic total gastrectomy is recommended between ages 20-30 years 1
  • Testing should begin in late teens or early 20s in families with early-onset disease 1

Familial Intestinal Gastric Cancer (FIGC)

• No robust screening recommendations exist for familial intestinal-type gastric cancer without polyposis 1
• H. pylori eradication is strongly advised in family members of patients with intestinal gastric cancer diagnosed before age 40 or in families with clustering of FIGC 1

Sporadic Family History (Non-Hereditary)

The most recent 2025 AGA guidelines provide the clearest pathway:

• If initial screening EGD shows no atrophy, metaplasia, or neoplasia in someone with a first-degree relative with gastric cancer:

  • Screening EGD should be considered every 3-5 years 1
  • This recommendation applies particularly when combined with persistent H. pylori infection despite eradication attempts 1

• If moderate to severe atrophy and/or multifocal gastric intestinal metaplasia is found:

  • Surveillance EGD should be considered every 3 years 1
  • Shorter intervals may be advisable with multiple risk factors 1

Quantifying the Risk

The evidence demonstrates that family history confers meaningful but variable risk:

• Overall relative risk with any first-degree relative: RR 1.83-2.08 2
• Sibling history confers higher risk than parental history: RR 3.18 vs. RR 1.66 2
• Two or more first-degree relatives with gastric cancer: RR 2.81 2
• Combined family history and H. pylori infection: RR 4.03 2

Critical Implementation Details

H. pylori Management

All individuals with family history of gastric cancer who test positive for H. pylori should undergo eradication therapy and confirmation of eradication 1. The synergistic effect of H. pylori and family history substantially increases gastric cancer risk 2, 3.

Timing to Initiate Screening

Begin screening 10 years prior to the age of onset in the affected relative, though this is based on expert opinion rather than high-quality evidence 3. For individuals without a specific age reference, the 2025 AGA guidelines suggest considering screening in the context of other risk factors including ethnicity and immigrant status 1.

Quality of Endoscopy

The screening EGD must be high-quality with:

• Systematic gastric biopsies if atrophy or metaplasia is suspected 1
• Targeted biopsies of any visual abnormalities 1
• Image-enhanced endoscopy techniques when available 1

Common Pitfalls

Do not apply hereditary diffuse gastric cancer protocols to all family history cases. HDGC represents a distinct entity requiring CDH1 testing and consideration for prophylactic gastrectomy, whereas sporadic familial clustering follows different screening algorithms 1.

Do not screen individuals with family history using the same intervals as average-risk populations. The 3-5 year interval for those with normal findings and family history is more intensive than would be recommended for average-risk individuals 1.

Recognize that screening intervals may need shortening to 2 years in individuals who have already developed precancerous lesions (atrophy or intestinal metaplasia) combined with family history 3.