Page 18 - Helicobacter pylori and Gastric Cancer: From Tumor microenvironment to Immunotherapy

Chapter 1
General introduction
Other Risk Factors
Socioeconomic status (SES) and surrogate factors
Developing countries share a higher burden of gastric cancer than in the developed world. This appears due to differences in socio-economic status. In developed countries, like The Netherlands, both incidence and mortality are currently decreasing, due in part to the slow disappearance of H. pylori that accompanied the uninterrupted access to better living conditions in people born after World War II. Indeed, within any country or population, noncardia gastric cancer is most often seen in lower socioeconomic groups and has been associated with many risk factors that act as a surrogate for lower SES, mainly low income, lower education, number of siblings, crowding, and lower occupational activity(36, 37). Hence, higher SES is inversely associated with gastric cancer of noncardia origin, whereas cardia gastric cancer is strongly associated with esophageal adenocarcinoma and both are associated with a higher SES. Many other factors involved in gastric cancer epidemiology are also associated with SES and probably confound some of the observed associations, although adjusting for H. pylori infection in a large European multicenter study, makes the effect of SES in non-cardia gastric cancer entirely disappear(38). Thus, although other factors such as fruit and vegetable consumption, cigarette smoking, and physical activity, may also confound any observed association with SES, it is clear that H. pylori is a major driving force in the development of gastric cancer, justifying my efforts of linking specific substrains of this bacterium to clinical outcome of disease.
Tobacco and alcohol
In relation to the former, smoking is a recognized cause of gastric cancer but seems to act as a moderate risk factor, compared to other associated risk factors of gastric adenocarcinoma. A meta-analysis and systematic review, (including cohorts, case- cohorts, and nested case-control studies and other prospective studies) produced a risk estimate for gastric cancer of 1.62 (1.50–1.75) in male smokers and an assessment of relative risk of 1.20(1.01–1.43) in female smokers as compared to self-reported never smokers(39). Meta-analyses studies have furthermore revealed that the risk for stomach cancer increases with increasing cigarette consumption (as expressed either as average number per day, number of pack-years, or as a function of a longer period of smoking)(40). Nevertheless, as compared to for instance lung
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