Aetiology
The risk of gastric cancer has been associated with consumption of smoked and salted foods and lack of refrigeration.[15] The widespread use of refrigeration has been cited as a reason for the decrease in the incidence of gastric cancer in the US since 1930.
Multiple studies have demonstrated an association between Helicobacter pylori and gastric cancer.[16][17][18][19][20][21] While H pylori affects half of the global population, gastric cancer develops in only around 3% of the infected individuals.[6][22] The progression to malignancy is thought to be driven by a chronic inflammatory process that causes tissue damage and subsequent epithelial changes.[21][23] However, this chronic inflammation mainly leads to the intestinal-type cancer and is not a necessary precursor for the diffuse-type, indicating the involvement of other pathways.[6]
Other risk factors include male sex (later-onset), female sex (early-onset), immigration from high-incidence regions, pernicious anaemia, consumption of foods containing N-nitroso compounds, high salt diet, smoking, and family history.[6][24][25]
Increased incidence of adenocarcinoma of the gastric cardia is believed, in part, to be attributable to increased obesity.[12]
Pathophysiology
Several events at the molecular level have been implicated in the development and progression of gastric cancers. Gastric cancer can involve loss of the tumour suppression gene, p53.[26] Several proto-oncogenes, such as ras, c-myc, and erbB2 (HER2), have been shown to be over-expressed in gastric cancers.[26] Helicobacter pylori has been associated with molecular events that could lead to gastric cancer, such as an increase in p53 mutations.[16]
Early-onset gastric cancer exhibits distinct molecular characteristics compared with later-onset gastric cancer, notably featuring a lower prevalence of somatic tumour variants (8% vs. 23%) and less frequent high microsatellite instability (3% to 6% vs. 23%). These genomic differences are observed despite the relatively higher frequency of Lynch syndrome in patients with early-onset gastric cancer.[14]
The Cancer Genome Atlas (TCGA) Research Network has classified gastric cancer into four major genomic subtypes. These subtypes have distinct features and molecular alterations: 1) tumours that are positive for Epstein-Barr virus; 2) microsatellite unstable tumours; 3) genomically stable tumours; 4) chromosomal unstable tumours. This classification might be helpful to guide patient therapy in the future.[27]
Classification
Lauren classification[1]
Diffuse (occurs more often in young patients and has a worse prognosis than intestinal type)
Intestinal (frequently exophytic and ulcerated tumours and occurs in the proximal and distal stomach more often than diffuse type)
Japanese Endoscopy Society classification[2]
Type I: polypoid or mass-like tumours
Type II: flat, or either minimally elevated or depressed, tumours
Type III: tumours are associated with an ulcer
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