Page 15 - Helicobacter pylori and Gastric Cancer: From Tumor microenvironment to Immunotherapy

Prognosis following a gastric cancer diagnosis is usually poor. This is evident from the pattern of mortality which shows great similarity that of the incidence of gastric cancer,, and the proportional breakdown of the key two indicators by continent does not seem substantially different (see Fig. 2). The above estimates represent the figures for cases of the histological type of cancer known as gastric adenocarcinoma, but other types of gastric cancer exist as well. Several studies recently estimated a worldwide total of lymphomas of gastric origin in 2008 to be 18,000 (i.e., less than 2% of the number of adenocarcinomas)(23). Other gastric malignant histologies are even less frequent than this. Hence in this thesis, I focus on the adenocarcinoma of the stomach.
A recent study by Hu cum suis indicated a relationship between metabolic syndrome and increased risk for gastric adenocarcinoma(24). The main finding of Hu and colleagues is an important issue, not only for clinicians who are faced by gastric cancer patients but also for health policy makers in Asian countries, who are challenged with the burden of gastric cancers in their populations. We know that the problem of gastrointestinal cancer is growing due to aging populations, smoking, obesity, and changing lifestyle in Asia(25, 26), which are all associated with metabolic syndrome. Thus controlling metabolic syndrome will remain essential for managing the cancer burden in the Asian population. As I am skeptical that important improvements in this respect will be made anytime soon, I feel that the need to develop more insight into gastric cancer pathogenesis and to develop new modes of treatments will remain necessary and this what I intend to aid through this thesis. I shall focus on H. pylori as a risk factor, the role of endoscopy in diagnosis, the potential of targeting Hedgehog signaling and the potential of checkpoint inhibitors in gastric cancers. The reason for these choices I shall try to explain below.
Risk factors for gastric cancer
Helicobacter pylori
It is assumed that H. pylori-infected individuals were once ubiquitous in the human population, but in many populations, the prevalence is successively declining as determined in birth cohorts and it is rare among children in Japan, Western Europe, North America, and Oceania(27). Risk factors associated with H. pylori infection, and thus gastric cancer, include overcrowding, poor sanitation and low
Chapter 1
General introduction
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