Page 19 - Helicobacter pylori and Gastric Cancer: From Tumor microenvironment to Immunotherapy

cancer, the effects of smoking are small with respect to development of cancer in the stomach and thus I decided not to investigate this aspect in the studies described in this thesis, but focus on other factors in their relation to gastric cancer.
Food and nutrition
In 2007 an expert panel assembled by the American Institute for Cancer Research scored the risk for cancer development in relation to diet and nutrition on a five-tier scale and concluded that an association between diet and gastric cancer exists(41). According to this panel, protective effects of diet on the development of gastric cancer emanating from various studies could be scored mostly as level 1 (convincing) evidence, but a few studies were scored as level 2 (probably) evidence. Probable protective factors are abstaining from carbohydrate intake and ample consumption of vegetables and fruits. Likely risk factors are high salt intake and consistently salt-preserved foods. For other dietary factors, scores were level 3 (limited evidence). Again, I decided to ignore this aspect of gastric cancer pathogenesis in my studies, as I found that other aspects were more deserving of study.
Epstein-Barr Virus
H. pylori is not the only infectious agent associated with malignant transformation in the stomach. Epstein-Barr virus (EBV) is present in 10% of gastric cancers. There is strong mechanistic evidence that EBV can provoke gastric cancer. EBV DNA appears incorporated in cancer cells as detected by the presence of antigen in gastric cancer(42). However, the epidemiological evidence that shows an association between gastric cancer and EBV is weak, mainly because of the difficulty of controlling for the confounding infection with H. pylori. For this reason, the same working group which concluded that H. pylori causes noncardia gastric cancer did not conclude that EBV causes gastric cancer(42) and as a consequence of this analysis I did not investigate EBV in relation to gastric cancer in this thesis.
Genetic Factors
Up to 3% of the total gastric adenocarcinoma burden is associated with an inherited predisposition syndrome(43). Among them, inherited gastric cancers of the diffuse type are prominent within this thesis I shall term as hereditary diffuse gastric cancer
Chapter 1
General introduction
12
17
1