H. Pylori Infection
Infection by H. pylori is strongly linked to non-cardia gastric cancer and gastric lymphoma, increasing risk by around sixfold [14, 15]. Once infected, the lifetime risk of developing gastric cancer is 1% . Importantly, the eradication of H. pylori reduces this risk .
Worldwide, 10% of gastric cancers are associated with EBV. The incidence of EBV-associated gastric cancers are highest in the USA and Germany, where it accounts for 16-18% of all gastric cancers . EBV infection is associated with PD-L1 overexpression . EBV-associated gastric cancer has a relatively favorable prognosis compared to other gastric cancers .
Obesity increases the risk of gastric cancer of the cardia, but its association with non-cardia gastric cancer is weaker [18, 19].
Smokers are more likely to develop gastric cancer, with dose and duration both contributing to risk [20, 21]. The association is especially strong in intestinal type gastric cancer and gastric cancer involving the cardia . After quitting, the risk of developing gastric cancer decreases over time, with an incidence approaching that of non-smokers after 10 years .
Heavy alcohol consumption has consistently been shown to increase the risk of gastric cancer, but the effects of lighter use are less clear [22, 23]. A nonlinear dose-response relationship may explain this finding .
It appears that high salt intake increases the risk of gastric cancer. In contrast, fruits and vegetables may have a protective role, possibly mediated by vitamin C .
Adjusted for age, men are approximately twofold more likely to develop gastric cancer [10, 26]. Men are projected to account for 2200 of the 3500 annual cases of gastric cancer in Canada .
The incidence of gastric cancer increases with age. Among those newly diagnosed with gastric cancer, 93% are at least 45 years old .
Race and Ethnicity
Geographically, the incidence of gastric cancer is highest in East Asia and Eastern Europe . Some of this risk persists in the offspring of parents who migrate to the West .
Family history and genetics
Positive family history appears to increase the risk of gastric cancer by 1.5 to 3.5 fold in most studies, independent of H. pylori infection and dietary contributions . However, fewer than 3% of gastric cancers are considered hereditary. The most common of the hereditary gastric cancers is hereditary diffuse gastric cancer, in which germline mutations of the CDH-1 gene are most strongly implicated. Rarer hereditary causes of gastric cancer include Lynch syndrome, familial adenomatous polyposis, Li-Fraumeni syndrome, and Peutz-Jeghers syndrome .