What is stomach (gastric) cancer?

Gastric cancer (GC) or adenocarcinoma is a highly malignant, fast-growing cancer.¹¹ The fourth most frequently diagnosed cancer worldwide, gastric cancer is also the second leading cause of cancer-related death.⁵ GC is a multifactorial disease, meaning both environmental and human factors are important to its pathogenesis, with many patients already presenting partial metastasis at diagnosis.^10,11 

Major risk factors include Helicobacter pylori infection, diets high in salt and smoked foods, smoking, and genetic conditions such as hereditary diffuse gastric cancer (CDH1 mutation) and Lynch syndrome.^8,5 Knowledge of the key risk factors aids prevention and early detection of GC. Nonspecific symptoms like weightloss and abdominal pain are typically the early symptoms which leads to frequent delays in diagnosis, resulting in a poor prognosis.¹⁵ However, early detection and treatment of H. pylori can significantly reduce the risk of developing gastric cancer.^5,7

Key risk factors

Infections

• H. pylori (primary risk)
  • Class I carcinogen (IARC); Chronic infection leads to chronic inflammation of the stomach mucosa and the eventual replacement of these cells by intestinal metaplastic cells, eventually transforming to cancer^7,10
• Epstein-Barr virus 
  • Although less common it is associated with ~10% of gastric cancers⁸

Lifestyle

• Dietary factors play a huge role in increasing the incidence of gastric cancer including but not limited to:
  • High intake of smoked/salty/pickled foods
  • Low intake of fruits/vegetables
  • High intake or red/processed meat¹
• Smoking
  • Reports indicate approximately 11% of gastric cancer cases globally are associated with smoking
  • Those with a history of smoking have a 1.5-2.5% increased risk of cancer developing compared to that in non-smokers
  • Cigarettes contain toxic and carcinogenic substances that damage DNA, causing abnormalities in bodily cell growth leading to cancer^1,3
• Heavy alcohol use has been associated with GI cancers as alcohol is classified as a class 1 carcinogen⁶
  • Acetaldehyde is a by-product of ethanol (alcohol) which disrupts DNA production leading to cellular mutations and the development of cancer^2,6

Medical conditions

Medical conditions can elevate the risk of gastric (stomach) cancer by promoting long-term inflammation, tissue damage, and abnormal cellular changes. Below is a brief overview of how certain conditions contribute to this increased risk:

• Chronic gastritis (inflammation of the mucosal lining of the stomach)^11,13
• Pernicious Anaemia -causes vitamin B12 deficiency, which leads to autoimmune destruction of parietal cells (cells which produce hydrochloric acid in the stomach), leading to absence of HCL in the stomach and causing intestinal metaplasia (transformation of cells in the tissue of the stomach to resemble cells of the intestines)¹²
• Intestinal metaplasia (a precancerous state)^10,13
• History of gastric polyps or ulcers^1,10
• History of gastrectomy or gastric surgeries^4,10,11 - this can cause long-term risk due to bile reflux creating a precancerous environment
• History of oesophageal cancer
  

Genetic & family history

• Family history of stomach cancer.
  • Having an immediate family member with gastric cancer is a lifelong risk factor for gastric cancer, however, the likelihood of developing the gastric cancer in this circumstance varies depending on the ethnic group and with the geographic region in question^4,5
• Several inherited cancer predisposition syndromes exist. Although rare and accounting for a low percentage of cases, they do carry significant risk and include but are not limited to:
  • Lynch syndrome (HNPCC)
  • Hereditary Diffuse Gastric Cancer (HDGC) is a rare inherited cancer syndrome with autosomal dominant transmission, primarily caused by germline mutations in the CDH1 gene^5,9
  • Hereditary Nonpolyposis Colon cancer¹⁶
  • Familial Adenomatous Polyposis (FAP)¹⁶
  • Peutz-Jeghers syndrome¹⁷

Environmental risks

Gastric cancer incidences vary vastly throughout the globe, indicating that environmental factors may be an important contributor to cases of GC, with the leading environmental factors varying also per region.¹¹ 

• Occupational exposure:
  • Higher risk in workers with exposure to coal dust, rubber, working in metal industries/factories and asbestos
• Water quality/exposure
  • Drinking water polluted with traces of Nitrates/nitrites may increase risk¹¹
• Living in high-risk geographic regions where incidence is higher (e.g., East Asia, East Europe and South America)¹¹
• Soil pollution and soil element content 
• Air pollution¹¹

Demographics

Certain population characteristics influence the likelihood of both the incidence and outcome of developing gastric cancers:

• Age: Incidence rises after age 50¹³
• Sex: More common in males (approx. 2:1 ratio)
• Ethnicity/Region: Higher in East Asian, Latin American, and Eastern European populations 
• Socioeconomic Status (SES): Lower SES is associated with increased risk due to poor nutrition, crowded living conditions (higher H. pylori transmission), and limited access to healthcare

Prevention tips

Gastric cancer can be prevented by minimising exposure to carcinogenic factors, screening high-risk groups, and offering timely rehabilitative care.¹¹ Below are a number of measures and strategies which, when combined, can significantly reduce the incidence of GC.

There are two major primary prevention strategies for gastric cancer at a population level which would require a huge public health campaign: 

• Eradication of H. pylori infections
  • Screening and treatment, especially in high- risk populations, can significantly reduce GC^8,16
• Adaptation of a healthy diet
  • Eat healthy, limit intake of salted, smoked and processed foods
  • A mediterranean diet consisting of vegetables, legumes and fish is thought to be preventative against GC¹
  • Increase intake of fresh fruits and vegetables rich in antioxidants and fibre¹⁰

Secondary prevention strategies include:

• Screening of high-risk individuals
  • Genetic testing and regular endoscopies for those with family history or carriers of hereditary syndromes (e.g., CDH1 mutation, Lynch syndrome)
  • Typically only a possibility in geographic locations with accessible, high-quality health services with adequate financial and technical resources^15,10
• Quit smoking
• Limit alcohol consumption

Summary

In summary, gastric cancer arises from a multifactorial combination of risks, including infections such as Helicobacter pylori and Epstein–Barr virus, unhealthy dietary patterns, tobacco and alcohol use, genetic syndromes, and underlying medical conditions. Demographic factors like age, gender, ethnicity, and socioeconomic status also influence individual vulnerability. Recognising these risk factors is crucial for early and timely diagnosis, effective prevention, and the introduction of public health strategies to diminish the global impact of the disease. Key preventive modifiable measures include H. pylori eradication, healthier lifestyle choices, and regular monitoring of high-risk groups to reduce incidence and improve prognosis. However, looking to the future, prevention strategies continue to evolve, and the most effective approach may vary based on regional factors and cultural or societal priorities.