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Epidemilogy and risk factors for Gastric cancer DR.Mina tajvidi radiation oncologist

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Gastric cancer It has remained one of the most important malignant diseases with significant geographical, ethnic, and socioeconomic differences in distribution the most common forms of cancer worldwide (excluding non-melanoma skin cancers) are lung (12.3 percent), breast (10.4 percent), and colorectum (9.4 percent) while the top three causes of death from cancer are lung (17.8 percent), gastric (10.4 percent), and liver (8.8 percent)

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GEOGRAPHICAL VARIATION The incidence of gastric cancer varies with different geographic regions. Approximately 60 percent of gastric cancers occur in developing countries. Studies of Japanese migrants to the Unites States have confirmed that early exposure to environmental rather than genetic factors have a greater influence on mortality and incidence rates

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Intestinal gastric cancer is more common in males and older age groups. It is more prevalent in high-risk areas and is likely linked to environmental factors. The diffuse or infiltrative type, is equally frequent in both sexes, is more common in younger age groups, and has a worse prognosis than the intestinal type. There has been a worldwide decline in the incidence of the intestinal type in recent few decades that parallels the overall decline in the incidence of gastric cancer. By contrast, the decline in the diffuse type has been more gradual. As a result, the diffuse type now accounts for approximately 30 percent of gastric carcinoma in some reported series

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PRECURSOR LESIONS FOR INTESTINAL TYPE CANCERS Longstanding chronic superficial gastritis caused by chronic H. pylori infection, pernicious anemia, or possibly a high salt diet leads eventually to chronic atrophic gastritis and intestinal metaplasia. Gastric atrophy is accompanied by a loss of parietal cell mass and therefore a reduction in acid production (hypochlorhydria or achlorhydria), a decrease in luminal ascorbic acid (vitamin C) levels, and a compensatory increase in serum gastrin, a potent inducer of gastric epithelial cell proliferation.

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Diet Large epidemiologic studies demonstrating the association between diet and gastric cancer were based mainly upon the amount of food imported and produced rather than the actual food consumption Diets low in vegetables, fruits, milk, and vitamin A and high in fried food, processed meat, and fish and alcohol have been associated with an increased risk of gastric carcinoma in several epidemiologic studies Salt High salt intake damages stomach mucosa and increases the susceptibility to carcinogenesis in rodent

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Smoking Several studies have examined the relationship between tobacco smoking and gastric cancer. A meta-analysis of 40 studies estimated that the risk was increased by approximately 1.5 to 1.60-fold and was higher in men Alcohol A consistent association between alcohol consumption and the risk of gastric cancer has not been demonstrated [39,41]. A study from Europe suggested that daily intake of wine may be protective Socioeconomic status The risk of distal gastric cancer is increased by approximately twofold in populations with low socioeconomic status [42- 45]. By contrast, proximal gastric cancers have been associated with higher socioeconomic class

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Gastric surgery There is an increased risk of gastric cancer after gastric surgery, with the risk being greatest 15 to 20 years after surgery and then increasing with time Reproductive hormones Gastric cancer incidence rates are consistently lower in women than men in both high and low-risk regions worldwide.

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EBV-associated gastric cancers are characterized by DNA methylation of the promoter region of various cancer-associated genes, which silences the expression of these genes It is thought that Helicobacter pylori infection triggers inflammation at the corpus mucosa that results in atrophy and intestinal metaplasia. H. pylori infection has been associated with an approximate 6-fold increase in the risk with adenocarcinomas distal to the cardia, including both the intestinal and diffuse types.

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There are reports of multiple families worldwide with hereditary diffuse gastric cancer due to germline mutations of the E-cadherin gene CDH1 [81-83]. The disorder has an autosomal dominant pattern of inheritance. The lifetime cumulative risk for advanced gastric cancer has been estimated to be 40 to 67 percent in men, and 60 to 83 percent in women The human interleukin 1 beta (IL-1B) gene is the most important candidate gene in the host that could affect the clinical outcome of H. pylori

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Genetic polymorphisms Certain polymorphisms have been associated with gastric cancer Polymorphisms of methylenetetrahydrofolate (MTHF) reductase have been associated with gastric cancer, mainly in East Asians Hypertrophic gastropathy and immunodeficiency syndromes Hypertrophic gastropathy (including Menetrier's disease) [50] and various immunodeficiency syndromes [94,95] have been linked with gastric cancer

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The risk of gastric cancer was increased among patients with benign gastric ulcers (incidence ratio 1.8), unchanged among patients with prepyloric ulcers, and decreased among those with benign duodenal ulcers Pernicious anemiaincreased risk of intestinal- type gastric cancer. A two- to threefold excess risk has been reported Beta-carotene and ascorbic acid are believed to interfere with the progression to cancer through their antinitrosation and antioxidant effects, and thus act as protective factors

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SUMMARY Gastric ulcers, adenomatous polyps, and intestinal metaplasia have been associated with an increased risk of gastric cancer. (See above). Gastric cancer developing in patients considered to be at average risk involves an interplay of bacterial, host, and environmental facts. Dietary (nitroso compounds, high salt diet with low vegetables) and lifestyle factors (smoking and alcohol consumption) probably account for one-third to one-half of all gastric cancers. H. pylori infection, especially certain genotypes (vacAs1-, vacAm1-, and cagA-positive), remains an important risk factor. The risk is increased further in hosts who possess specific types of cytokine polymorphisms

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