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Chapter 1 - Epidemiology, risk factors and pathogenesis

Gastric Cancer

The high-risk areas for gastric cancer (GC) are Japan, China, Eastern Europe and certain countries in Latin America. Low-risk areas are North America, India, some Western European countries and most of Africa.

About 70% of cases occur in less developed countries, although in Europe there are high-risk areas in Portugal, central areas of Spain and Italy, and Eastern European countries.

Incidence rates have been declining worldwide, except for cardia GC, which has shown an increase in some developed countries, though it is still the fifth most common cancer worldwide.

A multifactorial and multistep model of gastric carcinogenesis is currently accepted, with different factors involved at different stages in the cancer process.

The GC development process undergoes a cascade from normal mucosae, through gastritis to atrophic gastritis, complete intestinal metaplasia (IM), incomplete IM, dysplasia and GC.

Pathogenesis differs between cardia and non-cardia GC.
H. pylori is probably a necessary condition for non-cardia GC, but it is not associated with cardia GC.

Several factors are, or may be, associated with either a decreased or increased risk of GC, including infections, tobacco use, dietary factors, high alcohol intake and body mass index (cardia GC).

SNPs (involved in inflammatory responses, activation of chemical compounds, DNA repair) might modify the effect of environmental exposures and could explain geographical variations.

Germline mutations in CDH1 and CTNNA1 cause the rare (1%-3%) familial form of diffuse GC. GWAS in Asia have found a significant association with several genes, the most relevant being PSCA and MUC1.

Revision Questions

  1. Which are the high-risk areas for GC in Europe?
  2. Do you agree that H. pylori infection is probably a necessary condition of non-cardia GC?
  3. What are the main factors that increase and decrease the risk of GC?
Oesophageal Cancer Colorectal Cancer

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