Gastric cancer (stomach cancer) begins in the lining of the stomach and remains a serious health concern worldwide. Although incidence is declining in many regions, it continues to pose major challenges in East Asia, Eastern Europe, and Latin America. Early detection is often difficult because symptoms may be subtle, while advanced disease requires complex treatment involving surgery, chemotherapy, and sometimes targeted or immune therapies.
In recent decades, screening programs in some countries have helped detect gastric cancer earlier, improving survival rates. Ongoing research is uncovering new genetic, molecular, and environmental insights that shape both prevention and therapy strategies.
Causes and Risk Factors
The main cause of gastric cancer is chronic infection with Helicobacter pylori (H. pylori), a bacterium that leads to long-term inflammation of the stomach lining
- Dietary factors: Diets high in salted, smoked, or pickled foods can irritate the stomach and promote cancer formation. In contrast, diets rich in fresh fruits and vegetables may offer protection.
- Smoking and alcohol: Both contribute to stomach lining damage and increase risk.
- Genetics: Mutations in the CDH1 gene are linked to hereditary diffuse gastric cancer (HDGC), sometimes requiring preventive surgery after genetic counseling.
- Other conditions: Pernicious anemia, Epstein–Barr virus infection, and chronic gastritis elevate risk. Poor living conditions may increase the chance of infection and delay diagnosis.
Global Impact and Epidemiology
Gastric cancer incidence varies by region. East Asia—especially Japan, Korea, and China—shows the highest rates. Men are generally affected more than women, and risk increases with age. In countries with organized screening programs, cancers are detected earlier, and survival outcomes are better.
Endoscopy-based national screening programs in high-incidence countries such as Japan and Korea are associated with earlier detection and lower mortality from gastric cancer
Development and Pathophysiology
Correa Sequence (Intestinal Type)
The intestinal-type pathway follows the Correa sequence: chronic H. pylori infection leads to gastritis, atrophy, intestinal metaplasia, dysplasia, and finally carcinoma
Diffuse Type
Diffuse-type gastric cancer develops differently. It involves poorly cohesive cells that infiltrate the stomach wall, often due to CDH1 mutations. The stomach may appear thick and rigid—a condition known as “linitis plastica.”
Inflammation and Cytokines
Chronic inflammation releases cytokines such as IL-1β and reactive oxygen species that damage DNA and encourage malignant transformation.
Molecular Subtypes
Modern genomic profiling has identified four key molecular subtypes—EBV-positive, MSI-high, genomically stable, and chromosomally unstable. These classifications guide targeted and immunotherapy approaches
Symptoms and Diagnosis
Early gastric cancer often produces mild symptoms such as bloating or indigestion. As it advances, patients may experience weight loss, abdominal pain, vomiting, or gastrointestinal bleeding. Diagnosis relies on upper endoscopy with biopsy, followed by staging through endoscopic ultrasound (EUS) or CT imaging.
Staging and Treatment Options
Gastric cancer treatment is based on the stage, tumor biology, and patient condition. The TNM system classifies depth (T), lymph node involvement (N), and metastases (M). Treatment is coordinated by multidisciplinary teams.
Similar diagnostic approaches are also used for other digestive conditions. Learn more about gastric ulcer symptoms and treatments to recognize early warning signs before complications arise.
Surgical Options
- Endoscopic resection: Endoscopic submucosal dissection (ESD) is appropriate for carefully selected early gastric cancers that meet established criteria.
- Gastrectomy: Partial or total gastrectomy with lymph node removal (D1 or D2). D2 lymphadenectomy is recommended in experienced, high-volume centers to ensure safety and improve long-term outcomes.
Non-Surgical and Systemic Options
- Perioperative chemotherapy: Used for locally advanced disease before and after surgery.
- Adjuvant therapy: Chemotherapy or chemoradiation may be given after surgery to lower recurrence risk.
- Metastatic disease: Managed with palliative chemotherapy, HER2-targeted drugs like trastuzumab, and immunotherapy (e.g., PD-1 inhibitors) guided by molecular biomarkers.
Prognosis and Prevention
Survival depends strongly on the stage at diagnosis. Early detection through endoscopy-based programs leads to better outcomes. Advanced and metastatic cancers have lower survival rates, emphasizing the importance of prevention and timely care.
Eradicating H. pylori infection is one of the most effective preventive steps. Studies show that H. pylori eradication can reduce gastric cancer risk by up to 50% in high-risk populations
Preventive care doesn’t stop with the stomach — maintaining a healthy colon also lowers overall gastrointestinal cancer risk. See our guide on colorectal cancer prevention and care to understand lifestyle habits that protect your digestive tract.
Other preventive actions include reducing salt-preserved foods, quitting smoking, moderating alcohol, and promoting fresh produce intake. In families with known CDH1 mutations, genetic counseling and risk-reducing surgery may be appropriate.
Future Directions and Conclusion
Advances in molecular profiling, AI-assisted endoscopy, and precision oncology are reshaping gastric cancer care. Liquid biopsies that detect tumor DNA in blood show promise for early detection and relapse monitoring. Immunotherapy and targeted combinations continue to improve outcomes in advanced disease. Researchers are also developing vaccines against H. pylori to enable long-term prevention.
In conclusion, gastric cancer remains a complex but increasingly manageable disease. Prevention through infection control and healthy lifestyle choices, coupled with timely diagnosis and multidisciplinary treatment, provides the best path toward reducing its global impact.
Key Questions and Answers
Q1: What is the main risk factor for gastric cancer?
Chronic infection with H. pylori is the primary risk factor, driving inflammation that can lead to cancerous changes in the stomach lining.
Q2: How does the Correa Sequence explain gastric cancer development?
It describes a gradual transition from chronic gastritis to atrophy, intestinal metaplasia, dysplasia, and finally cancer—typically linked to H. pylori infection.
Q3: What are the treatment options for early-stage gastric cancer?
Carefully selected early cancers can be treated with endoscopic submucosal dissection (ESD). Larger or deeper tumors usually require gastrectomy with D2 lymphadenectomy performed in experienced centers.
Q4: How do molecular subtypes affect treatment?
Genomic subtyping (EBV-positive, MSI-high, etc.) helps guide targeted and immunotherapy choices for better personalization of treatment.
Q5: How can gastric cancer be prevented?
Key preventive strategies include H. pylori eradication, improved diet, smoking cessation, and genetic counseling for families with hereditary risk.