In 2018, 4.8 million new cases of gastrointestinal (GI) cancers and 3.4 million related deaths were recorded globally, with the highest prevalence in Asia, placing stomach cancer among the leading causes of cancer-related mortality worldwide (35%). Despite medical advancements, stomach cancer is often diagnosed too late due to its silent nature in the beginning, so this delay significantly limits treatment options and worsens outcomes.1 With risk factors from age, sex, blood type, family history, and genetic conditions such as Lynch syndrome and hereditary gastric cancer (HDGC) that significantly increase the risk of stomach cancer, it is therefore important to recognise and understand the risks and science behind this detrimental disease.2
The stomach is a major component of the digestive system that sustains life through the breakdown of food. But when an imbalance of abnormal cell growth occurs, stomach cancer manifests in many different forms, with some rarer types that begin in the nerve cells, immune cells, and hormone-producing cells of the stomach to form tumours. The most common type of stomach cancer, accounting for 90% of cases, adenocarcinoma, begins within the glandular cells that secrete mucus in the stomach lining.3 This means that diagnosing the exact type and location of stomach cancer is important because it directly determines symptom presentation and shapes the course of treatment.
Stomach cancer is a disease that doesn’t usually make a loud entrance and often hides in plain sight. In the early stages, the subtle signs are easily ignored as they might cause nothing more than mild indigestion, a sense of fullness after eating small amounts, and unexplained weight loss and fatigue. The vague symptoms lead to late detection, which enables the cancer to grow and spread for months or even years beyond the stomach lining, which makes this disease so dangerous. Around 60% of stomach cancers are diagnosed in the advanced stage, where symptoms include vomiting with blood, black stools, persistent abdominal pain, and difficulty in swallowing. Tumours cause these complications by blocking the food passage, bleeding from ulcerated tumours, and disrupting normal acid and enzyme secretion.1,4
The complications of stomach cancer lie in that it is a multifactorial disease triggered by both lifestyle choices and environmental risk factors; this type of cancer is one of the most lethal malignant tumours.2 However, scientists have been able to identify several well-established links; understanding these can help individuals make educated choices to lower the risk of stomach cancer.
One of the most well-known causes of stomach cancer is caused by a bacterium called Helicobacter pylori. This bacterium invades the lining of the stomach, which causes chronic irritation that can progress into cancer. Helicobacter pylori is very commonly found in developing countries where up to 76% of adults may carry the infection, which increases the risk of stomach cancer by three to six times compared to individuals without the infection.2
Where you live and even your ethnic background can directly affect your risk. It is especially a huge health challenge in Asia (75% of new cases). This suggests that inherited traits and early life exposures play a huge role.2
There is an 82% increase in the risk of stomach cancer for heavy smokers. Furthermore, eating an imbalanced diet makes individuals more vulnerable.2
Usually diagnosed between the ages of 60-80. The prevalence in people assigned male at birth is twice as common as in people assigned as female at birth, although the reason behind this is still being studied. One theory is that the female hormones may offer some protection.2,4,5
Chronic acid reflux (GERD) can increase a stomach cancer type that is known as gastric cardia cancer. Obesity and a history of stomach surgeries may also increase risk due to the alteration in the stomach environment.2
Some genetic disorders, including HDGC, can cause mutations or deletions in genes, such as tumour suppressor genes, p53, that increase the risk of stomach cancer.2
The risk of stomach cancer is shaped by a mix of genetic and environmental factors, which sometimes cannot be controlled. However, by changing habits that we can manage, like diet and smoking, some risks can be reduced through healthier choices.4,5
Under normal conditions, the perfect balance between cell growth and cell death is controlled to maintain the optimal functions of our stomachs. But in stomach cancer, this equilibrium is disrupted, so abnormal cells start to grow uncontrollably and acquire the ability to invade nearby tissues. In 60% of the cases, Helicobacter pylori infection is the initial trigger that causes chronic stomach inflammation. In some cases, dietary factors such as high salt intake, smoked foods, and processed meats promote DNA damage. Low fruit and vegetable intake does not provide the protective antioxidants the body needs.4
The precancerous stage is marked by the bacterium altering the stomach environment, which erodes the stomach lining with the thinning of mucosal cells and creates an irreversible low-acid environment.2 In advanced stages of a specific type of stomach cancer named intestinal-type adenocarcinoma, the stomach lining cells transform into intestinal-type cells as a repair mechanism, and changes in important genes occur, including Tumour Protein p53 (TP53).
This gene usually acts as a lubricant against cancer, but its error disables tumour-suppressing functions, allowing damaged cells to persist. Diffuse-type adenocarcinoma that is linked to CDH1 (a protein named E-cadherin, which plays a crucial role in helping cells stick together) mutations can infiltrate the stomach walls directly because the ‘glue’ that holds the cells together is lost, which allows cancer cells to spread more easily.6
The tumour microenvironment alters to its favour to create a safe zone so it can secrete messenger proteins, such as Interleukin-6 (IL-6) which plays a key role in the body’s immune system to form new blood vessels for nutrient supply to feed the tumour, use signals like Transforming Growth Factor Beta (TGF-β) to silence immune attacks, and invite M2 macrophages (a type of immune cell that plays the role in healing and repair) to help it grow. At this stage, these cancer cells can breach the basement membrane. They can penetrate from the innermost stomach layers, such as the mucosa, submucosa and muscle layers, to invade some adjacent organs, including the pancreas and liver.4,5
Stomach cancer spreads in different ways. Some key factors affecting the spread of stomach cancer include the origin of the tumour, cancer type, and gene changes.2 The cancer cells can spread in several ways:
Although early detection immensely improves the course of direction of stomach cancer, the ambiguous warning signs of stomach cancer are often disregarded because of the signs it shares with indigestion and other common digestive issues. Key diagnostic tools for stomach cancer include a complete blood count (CBC) to check for anaemia, stool tests, and upper endoscopy (EGD) with biopsy.1
For a more accurate diagnosis, physicians may choose to utilise more advanced techniques like chromo-endoscopy to help highlight even subtle changes in the mucosa that may indicate early stages of stomach cancer.4,5 The cancer will then be classified into a stage ranging from 1-4 to determine prognosis and course of treatment using the Tumour, Node, Metastasis (TNM) staging system.
Currently, gastrectomy, the surgical removal of part or all of the stomach, is the only curative treatment. Chemotherapy and radiation may be used before or after surgery to kill fast-growing cells, but are mainly palliative in late stages to manage pain and quality of life. Unfortunately, conventional chemotherapy drugs such as fluorouracil, cisplatin, and mitomycin are less effective due to late-stage diagnosis.4,5
While there is no guaranteed way to prevent stomach cancer, risk can be reduced through lifestyle choices: avoid smoking and maintain a balanced diet with a mindful intake of sodium. Pay attention to persistent irregular digestive symptoms and seek medical advice promptly if you are experiencing any indications of stomach cancer. Regular stomach cancer screening should be encouraged for those with high-risk factors, including family history and Asian ethnicity, residing in high-risk areas.
The prognosis and chances of long-term recovery from stomach cancer largely depend on the stage of diagnosis. Most cases are diagnosed at later stages, so the 5-year survival rate significantly drops to around 10-15%, but if detected early, the survival rate can be 90% or higher.
Stomach cancer remains a global health challenge because it can not show any symptoms, or it can present symptoms that mimic minor health issues. This complex disease is often caught too late when it has already overtaken normal stomach functions and spread through the blood, lymphatic system, and peritoneum. But understanding the signs, risk factors, and mechanisms behind its progression empowers us to take control of the condition by increasing awareness of stomach cancer. Surveillance in high-risk populations and simple modifications in lifestyle choices can remarkably reduce the frequency of presentation and mortality from stomach cancer.
