Genetic Variations and Gastric Cancer Risk

Abstract

Gastric cancer used to be the leading cause of cancer deaths in the world until the 1980 when it was overtaken by lung cancer.1 Nowadays, stomach cancer is the second leading cause of cancer death in both sexes worldwide. In spite of worldwide global decrease, in 2020 (using computing models), the prevalence of gastric cancer is expected to rise in Portugal, for both sexes (Globocan). Most patients die during the first year after the diagnosis, even if submitted to costly and aggressive therapy.2 Intestinal type is more frequently observed in older patients and represents the end product of a cascade of events that begin with multifocal atrophic gastritis after exposure to environmental risk factors like Helicobacter pylori (H. pylori) infection. This is usually accompanied by intestinal metaplasia and leads to cancer via dysplasia.3 This lengthy process, commonly known as Correa Cascade, is dependent on continued chronic inflammation.4--6 Unlike intestinal gastric cancer, the diffuse type typically develops following chronic inflammation without passing through the intermediate steps of glandular atrophy and intestinal metaplasia. So far, H. pylori gastritis is the only universal precursor condition for this subtype of gastric cancer.7,8 Significant advances toward the understanding of gastric carcinogenesis have been achieved since the identification of H. pylori by Marshall and Warren in 1984,9 and its latter classification as a class I carcinogen by the International Agency for Research on Cancer. Colonization is usually asymptomatic and tumor progression only occurs in a subset