2nd most common cause of cancer-related death in the world
remains difficult to cure as most present late
14th most common cancer in Western cultures and ranks about 7th in cancer causes of mortality, and median age at Dx is around 70yrs, with 25% present with localized disease, 31% with regional disease, 32% with metastatic disease
40% of cancers develop in the lower part, 40% in the middle part, and 15% in the upper part
90-95% of all gastric malignancies are adenocarcinoma of the stomach
pre-malignant phases:
chronic atrophic gastritis is the first histopathologic lesion of the preneoplastic cascade
high prevalence in Japan, Andean regions of South America, and Eastern Europe
diet vs genetics
early environmental exposure, rather than genetic factors, appear to have a greater influence on risk
10% are familial (independent of H.pylori infection)
diffuse type – strongly correlated with mutations in E-cadherin gene, CDH1
risk for people carrying these rare mutations in the E-cadherin gene have 70% chance if male and 56% if female (and these woman also have 42% chance of lobular breast cancer 1)
methionine metabolites produced by Streptococcus anginosus increase the risk - methionine enhances the expression of MAT2A and increases its transport into cells. This process supplies energy to tumor cells and promotes their growth. 3)
risk decreased by: Akkermansia muciniphila and various butyrate-producing species