Stomach Cancer

^ Stomach cancer (or gastric cancer) is the second most frequent cause of cancer death worldwide with almost 1 million new cases per year. It poses a serious health problem because of its low cure rate and its severe impact on the quality of life. Fortunately, its incidence has plummeted in many industrialized countries for several decades. The causes of this unique decrease are presumed in improved hygiene, altered diet, and widespread use of antibiotics reducing the prevalence of Helicobacter pylori infection.

> Helicobacter pylori infection is associated with most cases of stomach cancer. About 50% of the world population carry strains of the bacterium, but <10% develop inflammatory disease and ulcers, and even fewer stomach cancer. The outcome of the infection is determined by genetic variability of the germ and of the host which act in a strongly synergistic fashion. In the bacterium, variations in babA2, cagA, and vacA genes and in the host, polymorphisms in cytokine genes, particularly IL1B, influence the risk of chronic inflammation, ulcers, and cancer. Furthermore, carcinogenesis is dependent on cofactors, such as dietary carcinogens and protective ingredients.

> Most stomach cancers arise in the antrum and corpus. The predominant histological subtypes are the intestinal type and the diffuse type. The intestinal type develops from gastric atrophy in areas of intestinal metaplasia. The highly invasive diffuse type consists of small groups of easily scattering undifferentiated cells. Both histological types share some alterations such as the TP53 inactivation.

> Intestinal metaplasia is associated with altered expression of transcription factors that regulate the segmentation of the gut tube during fetal development. From benign metaplasia, intestinal-type gastric cancer develops in a fashion resembling colon carcinoma in some respects.

> The most distinctive alterations in diffuse-type stomach cancers are mutations of the CDH1 gene encoding E-Cadherin. Rare familial cases of this cancer type are caused by germ-line mutations in E-Cadherin. So, CDH1 behaves as a classical tumor suppressor gene in this specific cancer type.

^ The decreased incidence of 'classical' gastric cancer in industrialized countries is partly offset by a rising incidence of cancers of the esophagus and the upper parts of the stomach. These cancers are associated with alcohol consumption and smoking, and they may be promoted by enhanced acidity of the stomach juice as a consequence of H. pylori eradication. They are also typically associated with metaplasia.

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