What screening is recommended for stomach cancer in patients with a family history of the disease, particularly those who have had a first-degree relative die from it?

Screening for Gastric Cancer in Patients with Family History

For patients with a first-degree relative who died from gastric cancer, screening recommendations depend critically on whether the family meets criteria for hereditary diffuse gastric cancer (HDGC) versus familial intestinal gastric cancer (FIGC), with genetic testing and endoscopic surveillance being the cornerstone of management.

Hereditary Diffuse Gastric Cancer (HDGC) Screening

If your patient's family meets HDGC criteria, genetic testing for CDH1 mutations is mandatory and should guide all subsequent management. 1

HDGC Criteria and Genetic Testing

• Genetic testing for CDH1 is recommended in families meeting International Gastric Cancer Linkage Consortium (IGCLC) criteria, which include: two or more documented cases of diffuse gastric cancer in first- or second-degree relatives with at least one diagnosed before age 50, or three or more cases of diffuse gastric cancer in first- or second-degree relatives at any age 1
• Testing should include both DNA sequencing and large rearrangement analysis 1
• Testing can begin from late teens or early 20s in families with early-onset diffuse gastric cancer 1

Management for CDH1 Mutation Carriers

• Prophylactic total gastrectomy is recommended between ages 20-30 years for confirmed CDH1 mutation carriers 1
• For those declining gastrectomy, annual endoscopy surveillance with a minimum of 30 random biopsies is required 1
• Recent evidence suggests endoscopic surveillance can detect occult signet ring cell carcinoma effectively, with 63% of patients having cancer detected during surveillance endoscopies, though this remains controversial as an alternative to surgery 2
• Female CDH1 carriers require annual breast MRI starting at age 30 1

Familial Intestinal Gastric Cancer (FIGC) Screening

For families with intestinal-type gastric cancer (the more common type) without polyposis syndromes, screening recommendations are less robust but still clinically important.

When to Initiate Screening

• Begin screening 10 years before the age at which the affected relative was diagnosed with gastric cancer 3, 4
• For relatives of patients diagnosed with gastric cancer before age 50, screening should start significantly earlier—patients with parents diagnosed before age 50 developed gastric cancer approximately 10 years earlier than those without family history 4
• If the affected relative's age at diagnosis is unknown, consider starting screening at age 40 1

Screening Protocol

• Helicobacter pylori testing and eradication is essential in all individuals with a family history of gastric cancer, as there is a synergistic effect between H. pylori infection and family history 1, 3
• Optimal timing for H. pylori eradication may be around age 20, before significant precancerous lesions develop 3
• Upper endoscopy with systematic biopsy protocol is the screening method of choice 5
• A pilot screening program found 44% of asymptomatic first-degree relatives had gastric intestinal metaplasia (GIM) and 7% had low-grade dysplasia 5

Surveillance Intervals

• For individuals who have developed precancerous gastric lesions (atrophy or intestinal metaplasia), consider 2-year surveillance intervals rather than the standard 3-year interval 3
• This more intensive approach may improve early gastric cancer detection in high-risk individuals 3

Risk Stratification Considerations

High-Risk Features Warranting Screening

• First-degree relative with gastric cancer, particularly if diagnosed before age 60 1
• Multiple family members with gastric cancer across generations 1
• Racial/ethnic minorities or immigrants from high gastric cancer incidence regions (East Asia, Eastern Europe, parts of South America) 1
• Presence of additional risk factors: pernicious anemia, male sex, smoking, older age 1

What NOT to Screen

• Routine endoscopic surveillance is NOT recommended for patients with only gastric intestinal metaplasia without family history or other high-risk features 1
• Second-degree or third-degree relatives with gastric cancer do not require enhanced screening beyond standard recommendations 1

Critical Pitfalls to Avoid

• Do not assume all familial gastric cancer is HDGC—intestinal-type familial gastric cancer is more common but has different management 1
• Verify the histologic type of gastric cancer in the affected relative (diffuse vs. intestinal type) as this fundamentally changes screening strategy 1
• Document the age at diagnosis of the affected relative as this determines when to initiate screening 3, 4
• Be aware that scar tissue from previous biopsies can hinder detection of small white lesions typical of HDGC 6
• Family history information is often incomplete or inaccurate—attempt to verify diagnosis and age of onset in affected relatives when possible 7

Practical Algorithm

1. Obtain detailed family history: number of affected relatives, their relationship to patient, age at diagnosis, histologic type if known
2. Assess for HDGC criteria: if met, refer for genetic counseling and CDH1 testing 1
3. If CDH1 positive: offer prophylactic gastrectomy age 20-30 or annual endoscopy with extensive biopsies 1
4. If HDGC criteria not met (more common scenario):
   • Test and eradicate H. pylori 3
   • Begin endoscopic screening 10 years before affected relative's age at diagnosis 3, 4
   • Use systematic biopsy protocol to assess for precancerous lesions 5
   • If precancerous lesions found, consider 2-year surveillance intervals 3