Definition and Roadmap (Clear Objective)
Gastric cancer is a malignant neoplasm that originates in the stomach, most commonly from the glandular epithelial cells lining the gastric mucosa. The majority of cases are classified as adenocarcinomas, though other histological subtypes exist. According to global cancer surveillance data, gastric cancer remains one of the leading causes of cancer-related mortality worldwide. The objective of this article is to present a systematic explanation of gastric cancer by addressing:
- Basic pathological and clinical definitions.
- Mechanisms of carcinogenesis and biological progression.
- Epidemiology and risk determinants.
- Diagnostic methods, staging systems, and treatment categories.
- Outcomes and ongoing research directions.
- Frequently asked technical questions.
The structure follows the sequence: objective definition → foundational concepts → mechanisms → full scope discussion → summary and outlook → Q&A.
1. Basic Concepts and Clinical Foundations
Gastric cancer most frequently arises from the inner lining of the stomach. Approximately 90% of cases are adenocarcinomas, meaning they originate from mucus-producing glandular cells. Other subtypes include gastrointestinal stromal tumors (GISTs), lymphomas, and neuroendocrine tumors, though these are less common.
From an anatomical perspective, the stomach is divided into regions: cardia, fundus, body, antrum, and pylorus. Tumors may arise in any of these regions, and anatomical location can influence clinical characteristics and epidemiological patterns.
Symptoms in early stages may be nonspecific and can include indigestion, epigastric discomfort, early satiety, nausea, or mild anemia. Advanced disease may present with weight loss, persistent vomiting, dysphagia (particularly for tumors near the cardia), or gastrointestinal bleeding. The absence of specific early symptoms contributes to delayed diagnosis in many regions.
Globally, gastric cancer accounted for an estimated 968,000 new cases and approximately 660,000 deaths in 2020, making it the fifth most commonly diagnosed cancer and the fourth leading cause of cancer deaths worldwide according to the World Health Organization’s GLOBOCAN database.
2. Core Mechanisms and Pathogenesis
2.1 Chronic Inflammation and Helicobacter pylori
One of the most established risk factors for non-cardia gastric cancer is chronic infection with Helicobacter pylori, a bacterium that colonizes the stomach lining. The International Agency for Research on Cancer (IARC) classifies H. pylori as a Group 1 carcinogen. Long-term infection may lead to chronic gastritis, atrophic gastritis, intestinal metaplasia, dysplasia, and eventually carcinoma. This multistep progression is sometimes described as the Correa cascade.
2.2 Genetic and Molecular Alterations
Gastric carcinogenesis involves accumulation of genetic and epigenetic alterations affecting oncogenes and tumor suppressor genes. Molecular classifications proposed by The Cancer Genome Atlas (TCGA) categorize gastric cancer into subtypes such as Epstein–Barr virus (EBV)-associated tumors, microsatellite instability (MSI) tumors, genomically stable tumors, and chromosomal instability tumors. These molecular distinctions reflect differences in pathogenesis and biological behavior.
2.3 Environmental and Dietary Influences
Dietary factors, including high intake of salted, smoked, or nitrate-preserved foods, have been associated with increased risk in certain populations. Conversely, diets rich in fresh fruits and vegetables have been associated with lower incidence in epidemiological studies.
2.4 Host Susceptibility
A small proportion of gastric cancers arise in the context of hereditary cancer syndromes, including hereditary diffuse gastric cancer associated with CDH1 gene mutations. These inherited forms account for a minority of total cases.
3. Epidemiology and Full Scope Discussion
3.1 Geographic Distribution
Incidence rates vary substantially by region. Higher rates are observed in Eastern Asia (including Japan, Republic of Korea, and China), Eastern Europe, and parts of Central and South America. Lower incidence is reported in North America and parts of Africa. Such variation reflects differences in infection prevalence, dietary patterns, socioeconomic factors, and screening practices.
3.2 Screening and Early Detection
Population-based screening programs have been implemented in certain high-incidence countries. For example, national screening initiatives in Japan and the Republic of Korea include endoscopic or radiographic screening for adults in specific age groups. These programs have been associated with higher detection of early-stage disease in those populations. In lower-incidence regions, routine population screening is generally not implemented, and diagnostic evaluation is typically symptom-driven.
3.3 Diagnosis and Staging
Diagnosis is established through upper gastrointestinal endoscopy with biopsy. Histopathological examination confirms malignancy. Imaging modalities such as computed tomography (CT), endoscopic ultrasound (EUS), and occasionally positron emission tomography (PET) are used for staging. The TNM staging system evaluates tumor depth (T), regional lymph node involvement (N), and distant metastasis (M). Stage at diagnosis significantly influences prognosis.
3.4 Treatment Modalities
Treatment strategies depend on stage, tumor location, histological type, and patient health status. Categories of treatment include:
- Surgical resection (partial or total gastrectomy with lymphadenectomy)
- Endoscopic mucosal resection or endoscopic submucosal dissection for selected early lesions
- Radiation therapy
- Targeted therapy and immunotherapy in selected molecular subtypes
According to data from the American Cancer Society, the overall 5-year relative survival rate for gastric cancer in the United States is approximately 32%, though survival varies widely by stage, exceeding 70% for localized disease and significantly lower for metastatic disease.
4. Objective Considerations and Limitations
Gastric cancer outcomes depend strongly on stage at diagnosis. Regions with established screening programs report higher proportions of early-stage detection, which correlates with improved survival statistics. However, survival comparisons between regions are influenced by differences in staging systems, healthcare access, and reporting methodologies.
Research into molecular classification and immunotherapeutic approaches continues to expand understanding of tumor heterogeneity. Despite advancements, challenges remain in early detection in low-incidence settings and in management of advanced metastatic disease.
5. Summary and Outlook
Gastric cancer is a malignant disease arising primarily from the gastric mucosa, most commonly as adenocarcinoma. It remains a significant global health concern, with substantial geographic variation in incidence and mortality. Established risk factors include chronic Helicobacter pylori infection, dietary exposures,use, and certain genetic predispositions. Diagnosis relies on endoscopic biopsy and staging through imaging and histopathology. Treatment approaches vary by stage and biological characteristics. Ongoing research in molecular classification and immunotherapy aims to refine stratification and therapeutic strategies.
Future developments are likely to focus on improved risk stratification, noninvasive biomarkers, and enhanced early detection in diverse populations.
6. Question and Answer Section
Q1: What is the most common type of gastric cancer?
Adenocarcinoma accounts for approximately 90% of gastric malignancies.
Q2: How significant is Helicobacter pylori in gastric cancer risk?
Chronic infection with H. pylori is classified as a Group 1 carcinogen and is a major risk factor for non-cardia gastric cancer.
Q3: Why do incidence rates vary between countries?
Differences in infection prevalence, diet, screening programs, socioeconomic factors, and healthcare access contribute to variation.
Q4: What determines prognosis?
Stage at diagnosis, tumor biology, patient health status, and response to therapy influence outcomes.
Q5: Is early-stage gastric cancer detectable?
Early-stage disease can be identified through endoscopic examination, particularly in regions where screening programs are implemented.
Data Source Links
https://gco.iarc.fr/today/data/factsheets/cancers/7-Stomach-fact-sheet.pdf
https://www.who.int/news-room/fact-sheets/detail/cancer
https://www.cancer.gov/types/stomach/hp/stomach-treatment-pdq
https://seer.cancer.gov/statfacts/html/stomach.html
https://www.iarc.who.int/wp-content/uploads/2018/07/pr157_E.pdf
https://www.cancer.gov/about-cancer/causes-prevention/risk/infectious-agents/h-pylori-fact-sheet
https://pubmed.ncbi.nlm.nih.gov/22810597/