Gastric adenocarcinoma is a cancer that starts in the gland cells lining the inside of the stomach. It accounts for the vast majority of stomach cancers, roughly 90% to 95% of all cases. Globally, stomach cancer is the fifth most common cancer and the fourth leading cause of cancer death, with about 1.1 million new cases and 770,000 deaths estimated in 2020 alone.
How It Develops
The stomach lining constantly produces mucus, digestive enzymes, and acid. Adenocarcinoma begins when the DNA in these gland cells accumulates enough damage to trigger uncontrolled growth. This process usually unfolds over years or decades, often progressing through stages of chronic inflammation, thinning of the stomach lining, and precancerous changes before a true cancer forms.
The single biggest driver of that chain is infection with the bacterium H. pylori, which roughly half the world’s population carries. Long-term infection creates a persistent inflammatory environment that speeds up cell turnover and increases the chance of harmful mutations. Certain strains of the bacterium are especially dangerous because they produce a protein called CagA, which gets injected directly into stomach lining cells and disrupts normal growth controls. Not everyone with the infection develops cancer, but the chronic inflammation it causes is the starting point for most cases of gastric adenocarcinoma.
Key Risk Factors
Beyond H. pylori, diet plays a measurable role. A large meta-analysis covering nearly 5 million people found that high salt intake raised stomach cancer risk by 25%, and even moderate salt intake increased risk by 20%. High consumption of pickled foods raised risk by 28%, and high processed meat intake by 24%. These effects likely stem from salt damaging the stomach lining directly and from chemical compounds formed during food preservation.
Other established risk factors include smoking, heavy alcohol use, obesity (particularly for cancers near the top of the stomach), a family history of stomach cancer, and certain inherited genetic syndromes. Men are diagnosed at roughly twice the rate of women. Geographic patterns are striking too: rates are highest in East Asia, Eastern Europe, and parts of South America.
Where in the Stomach It Grows Matters
Gastric adenocarcinomas are broadly split by location. Cancers in the lower portion of the stomach (distal) are more closely tied to H. pylori infection and dietary factors. Cancers near the top of the stomach where it meets the esophagus (proximal) are more associated with obesity and chronic acid reflux, and their incidence has been rising in Western countries even as overall stomach cancer rates decline.
Proximal tumors tend to behave more aggressively. They’re more likely to invade deeper layers of the stomach wall and are more often made up of poorly organized, undifferentiated cells. In studies comparing early-stage tumors by location, proximal cancers were roughly 3.5 times more likely to have invaded into deeper tissue than distal ones.
Intestinal vs. Diffuse Subtypes
Under the microscope, gastric adenocarcinomas fall into two main patterns. The intestinal type forms recognizable gland-like structures, similar to what you’d see in colon cancer. It tends to occur in older adults, is more common in men, and is more strongly linked to H. pylori and environmental factors. The diffuse type is made up of scattered, poorly connected cells (sometimes called signet-ring cells because of their appearance). It can occur at younger ages and is more often associated with inherited genetic mutations.
While diffuse-type tumors have a reputation for worse outcomes, the picture is more nuanced than it first appears. When researchers control for how advanced the cancer is at diagnosis, the difference in survival between the two types narrows considerably. What matters most is stage, not subtype.
Symptoms and Why Early Detection Is Difficult
Stomach cancer often causes no symptoms in its early stages, which is one of the main reasons it’s frequently diagnosed late. When early symptoms do appear, they mimic everyday digestive complaints: vague upper belly pain, indigestion, heartburn, or mild nausea. These are easy to dismiss or attribute to something routine.
As the cancer advances, symptoms become more distinct. Feeling full after eating very small amounts of food, unintentional weight loss, persistent vomiting, and fatigue are common. Vomiting blood or passing black, tarry stools signals bleeding from the tumor. If the cancer spreads, it can cause additional symptoms depending on where it lands: yellowing of the skin if it reaches the liver, visible lumps in the neck or collarbone area if it reaches lymph nodes, or swelling of the abdomen if fluid accumulates in the belly cavity.
How It’s Diagnosed
The gold standard for diagnosis is an upper endoscopy with biopsies. A thin, flexible camera is passed through the mouth into the stomach, allowing the doctor to visually inspect the lining and take tissue samples. Guidelines recommend collecting 5 to 8 biopsy samples, especially from ulcerated areas, to ensure enough tissue for both microscopic examination and molecular testing.
Advanced imaging techniques during endoscopy, such as narrow-band imaging, can highlight subtle surface details that might otherwise be missed. Endoscopic ultrasound helps determine how deeply a tumor has penetrated the stomach wall. For very early cancers confined to the surface layers, the tissue removal during endoscopy can sometimes serve as both the diagnostic test and the treatment in one procedure.
Staging and Survival Rates
Survival depends heavily on how far the cancer has spread at the time of diagnosis. The five-year relative survival rates break down sharply by stage:
- Localized (confined to the stomach): 75%
- Regional (spread to nearby lymph nodes or organs): 35%
- Metastatic (spread to distant parts of the body): 7%
These numbers underscore why catching the disease early makes such a dramatic difference. In countries like Japan and South Korea, where routine screening endoscopy is common, a much higher proportion of cases are caught at the localized stage. In most Western countries, the majority of patients are diagnosed with regional or metastatic disease.
Treatment Approaches
For early-stage cancers that haven’t penetrated beyond the surface lining, endoscopic removal of the tumor can be curative on its own. When the cancer has grown deeper but hasn’t spread to distant sites, surgery to remove part or all of the stomach is the primary treatment, often combined with chemotherapy before and after the operation to shrink the tumor and reduce the chance of recurrence.
For advanced or metastatic disease, treatment is tailored increasingly by the tumor’s molecular profile rather than its appearance alone. About 15% of advanced stomach cancers produce excess amounts of a protein called HER2 on their surface. These tumors respond to targeted therapy that blocks HER2, which became a standard treatment after a large trial showed it significantly extended survival when added to chemotherapy.
Immunotherapy has become another important option, particularly for tumors that express a protein called PD-L1 above a certain threshold. Analysis of multiple large clinical trials found that patients whose tumors had a PD-L1 score of 5 or higher benefited most from adding immunotherapy to chemotherapy, with a 30% reduction in the risk of death. This score is now routinely tested at diagnosis to guide treatment decisions. Patients whose tumors fall below that threshold see less clear benefit from immunotherapy, and treatment plans typically rely more on chemotherapy and targeted agents.
The Growing Global Burden
Despite declining rates in many parts of the world thanks to better sanitation, H. pylori treatment, and refrigeration replacing salt-based food preservation, the absolute number of stomach cancer cases is rising due to population growth and aging. Projections estimate the annual burden will climb to roughly 1.8 million new cases and 1.3 million deaths by 2040. The shift toward more proximal tumors in Western populations, driven by rising obesity and reflux disease, adds a new dimension to a cancer historically dominated by infection and dietary salt.