The single biggest cause of stomach cancer is a bacterial infection. Helicobacter pylori, a spiral-shaped bacterium that colonizes the stomach lining, is responsible for the majority of non-inherited cases worldwide. But the full picture involves diet, genetics, lifestyle habits, and even where you live. Nearly 970,000 new cases of stomach cancer were diagnosed globally in 2022, and the causes behind them vary in ways that are both well understood and, in some cases, preventable.
H. pylori: The Primary Driver
H. pylori infects roughly half the world’s population, though only a small fraction develop stomach cancer. The bacterium causes damage through a slow, multi-step process that unfolds over decades. Once it establishes itself in the stomach lining, it injects a protein called CagA directly into the cells of the stomach wall. This protein triggers a cascade of inflammatory signals, flooding the area with molecules that promote chronic inflammation.
That chronic inflammation is where the real damage begins. The infection generates large amounts of reactive oxygen species, essentially unstable molecules that directly damage DNA. These cause point mutations, breaks in both strands of the DNA helix, and other forms of genetic corruption. At the same time, the bacterium gradually suppresses your cells’ built-in DNA repair machinery. Early in infection, the body ramps up its repair response to cope with the oxidative stress. But over years of chronic infection, that repair capacity gets worn down, leaving damaged DNA uncorrected.
CagA also disrupts the physical connections between stomach lining cells. It binds to proteins that hold neighboring cells tightly together, breaking apart those junctions. This causes the cells to lose their normal orientation and structure, which makes them more prone to behaving like invasive cancer cells. The combination of relentless inflammation, accumulating DNA damage, and structural disruption of the stomach lining creates the conditions for cancer to develop, typically over 15 to 30 years.
How the Stomach Lining Changes Over Time
Stomach cancer rarely appears out of nowhere. It usually follows a well-documented sequence of changes in the stomach lining. Chronic inflammation from H. pylori (or other causes) first leads to atrophic gastritis, where the normal acid-producing cells are gradually lost. Next comes intestinal metaplasia, a condition where the stomach lining starts to resemble intestinal tissue. This is considered a precancerous state.
The progression is slow but measurable. Among people with intestinal metaplasia, about 0.25% per year develop stomach cancer. If mild to moderate dysplasia (increasingly abnormal cells) is present, that rate climbs to 0.6% annually. With severe dysplasia, the annual rate jumps to 6%. These numbers explain why doctors monitor people with known precancerous changes through periodic endoscopy rather than waiting for symptoms.
Diet and Preserved Foods
What you eat has a significant influence on stomach cancer risk, and this partly explains the dramatic geographic differences in how common it is. Diets high in salt-preserved, smoked, or pickled foods are consistently linked to higher rates. Salt damages the stomach lining directly, making it more vulnerable to carcinogens, and preserved foods contain nitrosamines and other compounds that can cause DNA mutations.
On the protective side, fruits and vegetables offer meaningful defense. A large meta-analysis found that moderate daily intake of key vitamins reduced stomach cancer risk substantially: vitamin C (about 100 mg per day, roughly the amount in one large orange) was associated with a 35% lower risk. Vitamin A showed a 36% reduction and vitamin E a 32% reduction at modest daily doses. Overall, consistent vitamin intake from food sources was linked to a 23% reduction in risk. The likely mechanism is that antioxidants neutralize the reactive oxygen species that damage stomach cell DNA.
Smoking and Alcohol
Smoking increases stomach cancer risk by about 60% compared to never-smokers, even after accounting for other factors like alcohol use. The risk grows with duration. Alcohol on its own has a more moderate effect: men who drank four or more alcoholic beverages per day had roughly a 50% increase in risk compared to non-drinkers. But the combination is where things get notably worse. Men who both smoked for 30 or more years and drank four or more drinks daily had a 124% increase in risk compared to men who did neither.
Obesity and Cancer Near the Esophagus
Not all stomach cancers are the same, and their causes differ depending on location. Cancers of the cardia, the top part of the stomach where it meets the esophagus, have a distinct risk profile. Obesity is a major driver here. Excess abdominal fat increases pressure on the stomach, promoting acid reflux into the esophagus and the upper stomach. Over 20% of cancers at the gastric cardia are attributable to excess weight. This type of stomach cancer has been increasing in Western countries even as other forms have declined, mirroring the rise in obesity rates.
Genetics and Family History
A small but important percentage of stomach cancers are hereditary. The most well-defined genetic cause involves mutations in the CDH1 gene, which produces a protein that helps cells stick together. People who carry this mutation face a lifetime risk of diffuse gastric cancer (a particularly aggressive form that spreads throughout the stomach wall rather than forming a distinct tumor) ranging from 37% to 70% in men and 25% to 83% in women by age 80. This condition, called hereditary diffuse gastric cancer, follows an autosomal dominant inheritance pattern, meaning a single copy of the mutated gene from either parent is enough to confer the risk.
Beyond CDH1, having a first-degree relative with stomach cancer roughly doubles or triples your risk even without an identifiable gene mutation. This likely reflects a combination of shared genetics, shared H. pylori exposure within households, and similar dietary habits.
Geography and Environmental Exposure
Where you live is one of the strongest predictors of stomach cancer risk. Japan has the highest incidence rate at 27.6 cases per 100,000 people, followed closely by South Korea at 27.0. China’s rate is 13.7. The United States, by contrast, sits at just 4.1 per 100,000. Men are affected at roughly twice the rate of women across all regions: Japan’s male rate is 40.9 per 100,000 compared to 15.9 for women.
These differences are driven primarily by H. pylori prevalence, dietary patterns (high salt and preserved food consumption in East Asia), and screening practices. Importantly, studies of people who migrate from high-risk to low-risk countries show that their children’s risk drops toward the local rate, confirming that environmental factors, not just genetics, are responsible for most of the geographic variation.
Occupational exposures also play a role. Workers in rubber manufacturing face roughly 2.5 times the risk of stomach cancer compared to the general population, likely due to chemical exposures including dust and industrial compounds. Coal and other dusty industries have also shown elevated rates.
Who Gets Screened
The United States has no routine screening program for stomach cancer in people at average risk, largely because incidence is relatively low. But screening with upper endoscopy is recommended for several higher-risk groups: people with chronic atrophic gastritis or pernicious anemia, those who’ve had part of their stomach surgically removed, people with a family history of stomach cancer, those with known genetic syndromes like CDH1 mutations, and immigrants from countries where stomach cancer is common. In Japan and South Korea, population-wide screening programs exist and are a major reason those countries catch stomach cancers at earlier, more treatable stages despite their high incidence rates.