Gastric Cancer H. pylori Associated

name: Gastric Cancer H. pylori Associated
creation_date: '2026-01-26T02:55:13Z'
updated_date: '2026-02-27T21:52:57Z'
description: >-
  Helicobacter pylori-associated gastric cancer represents the majority of gastric
  adenocarcinomas worldwide. H. pylori is classified as a Class I carcinogen by the
  IARC, with chronic infection driving a cascade from gastritis to atrophic gastritis,
  intestinal metaplasia, dysplasia, and ultimately carcinoma (the Correa cascade).
  Both intestinal and diffuse histologic types can arise in the setting of H. pylori
  infection, though intestinal-type adenocarcinoma follows the classic progression
  pathway. H. pylori eradication can reduce gastric cancer risk, particularly when
  performed before development of premalignant lesions.
categories:
- Gastrointestinal Cancer
- Infectious Cancer
- Bacterial-Associated Cancer
parents:
- gastric carcinoma
has_subtypes:
- name: Intestinal-Type Adenocarcinoma
  description: >-
    Well-to-moderately differentiated tumors with glandular architecture,
    arising through the classic Correa pathway of atrophic gastritis to
    intestinal metaplasia to dysplasia to carcinoma. More common in high-
    incidence regions and associated with H. pylori infection.
- name: Diffuse-Type Adenocarcinoma
  description: >-
    Poorly differentiated tumors with scattered single cells or small clusters
    infiltrating the gastric wall (signet ring cell carcinoma). Associated
    with CDH1/E-cadherin loss. Can also arise in H. pylori-infected mucosa
    but does not require intestinal metaplasia.
infectious_agent:
- name: Helicobacter pylori
  description: >-
    H. pylori is a gram-negative spiral bacterium that colonizes the gastric
    epithelium. Infection is acquired in childhood and persists lifelong if
    untreated. Approximately 1-3% of infected individuals eventually develop
    gastric cancer, with risk modified by bacterial virulence factors, host
    genetics, and environmental factors including diet.
  evidence:
  - reference: PMID:39004993
    supports: PARTIAL
    snippet: Gastric cancer is one of the major causes of cancer-related deaths worldwide, and infection with Helicobacter pylori and EBV, smoking and a salt-heavy diet have been shown to be risk factors for the development of gastric cancer.
    explanation: This abstract identifies H. pylori infection as a risk factor for gastric cancer, supporting the infectious etiology noted here.
  infectious_agent_term:
    preferred_term: Helicobacter pylori
    term:
      id: NCBITaxon:210
      label: Helicobacter pylori
pathophysiology:
- name: CagA-Mediated Oncogenic Signaling
  description: >-
    The cagA gene encodes the CagA oncoprotein, a major H. pylori virulence
    factor injected into host cells via a type IV secretion system. CagA
    is phosphorylated by host kinases and activates SHP-2, disrupting
    cell polarity, promoting proliferation, and inhibiting apoptosis.
    CagA-positive strains confer higher cancer risk.
  cell_types:
  - preferred_term: epithelial cell of stomach
    term:
      id: CL:0002178
      label: epithelial cell of stomach
  biological_processes:
  - preferred_term: cell population proliferation
    modifier: INCREASED
    term:
      id: GO:0008283
      label: cell population proliferation
  - preferred_term: apoptotic process
    modifier: DECREASED
    term:
      id: GO:0006915
      label: apoptotic process
  locations:
  - preferred_term: stomach
    term:
      id: UBERON:0000945
      label: stomach
  downstream:
  - target: Disrupted Cell Polarity
    description: CagA interacts with PAR1b/MARK2, disrupting epithelial architecture
  - target: SHP-2 Activation
    description: Phosphorylated CagA activates SHP-2 phosphatase, promoting cell motility
- name: VacA-Induced Cellular Damage
  description: >-
    VacA (vacuolating cytotoxin A) is a pore-forming toxin that induces
    vacuolation, mitochondrial dysfunction, and apoptosis in epithelial
    cells. It also suppresses T cell function, allowing bacterial persistence.
    Different VacA alleles (s1/s2, m1/m2) confer different cancer risk.
  biological_processes:
  - preferred_term: cellular response to cytotoxic stimulus
    modifier: INCREASED
    term:
      id: GO:0034620
      label: cellular response to oxidative stress
  downstream:
  - target: Immune Suppression
    description: VacA inhibits T cell activation and proliferation
- name: Chronic Inflammation (Correa Cascade)
  description: >-
    H. pylori induces chronic gastritis with infiltration of neutrophils,
    lymphocytes, and macrophages. Persistent inflammation generates reactive
    oxygen and nitrogen species that cause DNA damage. Over decades, this
    leads to atrophic gastritis, intestinal metaplasia, dysplasia, and
    ultimately adenocarcinoma.
  evidence:
  - reference: PMID:26668499
    supports: PARTIAL
    snippet: "This cascade is a dynamic process that includes lesions, such as atrophic gastritis, intestinal metaplasia and dysplasia."
    explanation: "Abstract describes the gastric precancerous cascade with atrophic gastritis, intestinal metaplasia, and dysplasia."
  biological_processes:
  - preferred_term: inflammatory response
    modifier: INCREASED
    term:
      id: GO:0006954
      label: inflammatory response
  - preferred_term: response to oxidative stress
    modifier: INCREASED
    term:
      id: GO:0006979
      label: response to oxidative stress
  downstream:
  - target: Atrophic Gastritis
    description: Chronic inflammation leads to loss of gastric glandular cells
  - target: Intestinal Metaplasia
    description: Gastric epithelium undergoes metaplastic change to intestinal-type
- name: CDH1/E-cadherin Inactivation
  description: >-
    Loss of E-cadherin function through somatic mutation, promoter methylation,
    or loss of heterozygosity occurs in diffuse-type gastric cancer and some
    intestinal-type tumors. E-cadherin loss disrupts cell-cell adhesion and
    activates Wnt/beta-catenin signaling, promoting invasion.
  genes:
  - preferred_term: CDH1
  biological_processes:
  - preferred_term: cell-cell adhesion
    modifier: DECREASED
    term:
      id: GO:0098609
      label: cell-cell adhesion
  downstream:
  - target: Loss of Cell Cohesion
    description: Enables single-cell infiltrative growth pattern
histopathology:
- name: Gastric Adenocarcinoma
  finding_term:
    preferred_term: Gastric Adenocarcinoma
    term:
      id: NCIT:C4004
      label: Gastric Adenocarcinoma
  frequency: VERY_FREQUENT
  description: Adenocarcinoma is the most common histologic type of gastric cancer.
  evidence:
  - reference: PMID:40647518
    supports: PARTIAL
    snippet: "with adenocarcinoma being the most "
    explanation: Abstract notes adenocarcinoma as the predominant histologic type in a gastric cancer cohort.

phenotypes:
- category: Gastrointestinal
  name: Abdominal Pain
  frequency: VERY_FREQUENT
  description: >-
    Epigastric pain or discomfort is the most common presenting symptom,
    often initially attributed to dyspepsia or peptic ulcer disease.
  phenotype_term:
    preferred_term: Abdominal pain
    term:
      id: HP:0002027
      label: Abdominal pain
- category: Gastrointestinal
  name: Early Satiety
  frequency: FREQUENT
  description: >-
    Feeling full after eating small amounts occurs due to reduced gastric
    capacity from tumor growth or impaired gastric motility.
  phenotype_term:
    preferred_term: Early satiety
    term:
      id: HP:0033842
      label: Early satiety
- category: Constitutional
  name: Weight Loss
  frequency: FREQUENT
  description: >-
    Unintentional weight loss is common and may be significant at
    presentation, reflecting reduced oral intake and catabolic state.
  phenotype_term:
    preferred_term: Weight loss
    term:
      id: HP:0001824
      label: Weight loss
- category: Gastrointestinal
  name: Nausea
  frequency: FREQUENT
  description: >-
    Nausea and vomiting may occur, particularly with tumors causing
    gastric outlet obstruction.
  phenotype_term:
    preferred_term: Nausea
    term:
      id: HP:0002018
      label: Nausea
- category: Gastrointestinal
  name: Dysphagia
  frequency: OCCASIONAL
  description: >-
    Difficulty swallowing occurs with tumors involving the gastroesophageal
    junction (cardia) or causing esophageal compression.
  phenotype_term:
    preferred_term: Dysphagia
    term:
      id: HP:0002015
      label: Dysphagia
- category: Gastrointestinal
  name: Gastrointestinal Bleeding
  frequency: OCCASIONAL
  description: >-
    Melena, hematemesis, or occult blood loss leading to iron deficiency
    anemia may occur from tumor ulceration.
  phenotype_term:
    preferred_term: Gastrointestinal hemorrhage
    term:
      id: HP:0002239
      label: Gastrointestinal hemorrhage
- category: Constitutional
  name: Anorexia
  frequency: FREQUENT
  description: >-
    Loss of appetite is a common early symptom, contributing to weight loss.
  phenotype_term:
    preferred_term: Anorexia
    term:
      id: HP:0002039
      label: Anorexia
biochemical:
- name: H. pylori Testing
  notes: >-
    H. pylori infection can be detected by urea breath test, stool antigen,
    serology, or biopsy-based tests. Serology may remain positive after
    eradication. All gastric cancer patients should have H. pylori status
    assessed.
- name: Serum Pepsinogen
  notes: >-
    Low serum pepsinogen I and low pepsinogen I/II ratio indicate gastric
    atrophy and increased cancer risk. Used as a screening marker in
    high-incidence populations, particularly Japan.
genetic:
- name: CDH1
  association: Somatic and Germline Mutations
  inheritance:
  - name: Autosomal Dominant
  notes: >-
    Somatic CDH1 alterations (mutation, deletion, methylation) occur in
    approximately 50% of diffuse-type gastric cancers. Germline CDH1 mutations
    cause hereditary diffuse gastric cancer (HDGC) syndrome with lifetime
    risk greater than 70%.
- name: TP53
  association: Somatic Mutations
  notes: >-
    TP53 mutations occur in approximately 30-50% of gastric cancers,
    particularly intestinal type. More common in advanced-stage disease.
- name: RHOA
  association: Somatic Mutations
  notes: >-
    RHOA mutations occur in approximately 15-25% of diffuse-type gastric
    cancer, affecting cell migration and invasion pathways.
- name: ARID1A
  association: Somatic Mutations
  notes: >-
    ARID1A, encoding a SWI/SNF chromatin remodeling complex subunit, is
    mutated in approximately 20% of gastric cancers, particularly those
    associated with EBV or microsatellite instability.
treatments:
- name: H. pylori Eradication
  description: >-
    Triple or quadruple therapy to eradicate H. pylori reduces gastric
    cancer risk, particularly when given before development of intestinal
    metaplasia. Also reduces risk of metachronous gastric cancer after
    endoscopic resection of early tumors.
  treatment_term:
    preferred_term: pharmacotherapy
    term:
      id: MAXO:0000058
      label: pharmacotherapy
- name: Surgical Resection
  description: >-
    Gastrectomy (subtotal or total depending on tumor location) with
    D2 lymphadenectomy is the standard curative treatment for resectable
    gastric cancer. Reconstruction maintains GI continuity.
  treatment_term:
    preferred_term: surgical procedure
    term:
      id: MAXO:0000004
      label: surgical procedure
- name: Perioperative Chemotherapy
  description: >-
    Perioperative FLOT (5-FU, leucovorin, oxaliplatin, docetaxel) is
    the standard of care for resectable locally advanced gastric cancer
    in Western countries, improving survival compared to surgery alone.
  treatment_term:
    preferred_term: chemotherapy
    term:
      id: MAXO:0000647
      label: chemotherapy
- name: Trastuzumab
  description: >-
    Anti-HER2 monoclonal antibody added to chemotherapy for HER2-positive
    (approximately 15-20%) advanced gastric cancer. First targeted therapy
    to show survival benefit in gastric cancer.
  treatment_term:
    preferred_term: pharmacotherapy
    term:
      id: MAXO:0000058
      label: pharmacotherapy
    therapeutic_agent:
    - preferred_term: trastuzumab
      term:
        id: CHEBI:231601
        label: trastuzumab
- name: Immune Checkpoint Inhibition
  description: >-
    PD-1 inhibitors combined with chemotherapy are now standard first-line
    treatment for advanced gastric cancer. Benefit is greatest in PD-L1
    CPS-high and MSI-high tumors.
  treatment_term:
    preferred_term: pharmacotherapy
    term:
      id: MAXO:0000058
      label: pharmacotherapy
disease_term:
  preferred_term: gastric carcinoma
  term:
    id: MONDO:0004950
    label: gastric carcinoma

classifications:
  icdo_morphology:
    classification_value: Adenocarcinoma
  harrisons_chapter:
  - classification_value: cancer
  - classification_value: solid tumor