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Gastric Cancer

Gastric Cancer

Overview

Gastric cancer is more common than esophageal cancer in Western countries but is less fatal. It is estimated that 21,320 new cases of gastric cancer will be diagnosed in the United States in the year 2012, with 10,540 deaths expected. Worldwide in 2012, gastric cancer developed in approximately 930,000 individuals annually, accounting for 10% of neoplastic deaths. The incidence and mortality of gastric cancer have been declining in most developed countries, including the United States; the age-adjusted risk (world estimate) fell 5% from 1985 to 1990.

Gastric cancers include malignant tumors arising from the region extending between the gastroesophageal junction and the pylorus; those arising in the stomach within 5 centimeters of the gastroesophageal junction and actually crossing it are considered esophageal cancers. It may not be possible to determine the site of origin if the cancer involves the gastroesophageal junction itself, a situation that has become more common in recent years.

Epidemiology

Gender

Gastric cancer occurs more frequently in men, with a male-to-female ratio of 2.3:1; mortality is approximately double in men.

Age

The incidence of gastric cancer increases with age. In the United States, most cases occur between the ages of 65 and 74 years, with a median age of 70 for males and 74 for females.

Race

Gastric cancer occurs more frequently in American blacks and Asians than in whites; in black males, it tends to occur at a younger age (68 years).

Geography

Evidence of an association between environment and diet and gastric cancer comes from the profound differences in incidence seen in various parts of the world. While relatively rare in North America and many European nations, gastric cancer is still common in Japan, the former Soviet Union, and parts of Central America and South America.

Survival

Most patients still present with advanced disease, and their survival remains poor. From 1999 to 2006, only 23% of patients with gastric cancer presented with localized disease. The relative 5-year survival rate for patients with gastric cancer of all stages is 26%.

Incidence

Significant increases in age-adjusted incidence rates for tumors arising in the gastric cardia have been seen in males. Rates for other gastric adenocarcinomas either have not significantly changed (black males) or have declined (white males). Overall, rates of gastric adenocarcinoma have fallen for men and women between 1975 and 2007.

Etiology, Risk Factors, and Prevention

Diet and Environment

Studies of immigrants have demonstrated that high-risk populations (eg, Koreans) have a dramatic decrease in the risk of gastric carcinoma when they migrate to the West and change their dietary habits. Low consumption of vegetables and fruits and high intake of salts, nitrates, and smoked or pickled foods have been associated with an increased risk of gastric carcinoma; those with refrigeration available may have some mitigation of the risk associated with high salt intake. Conversely, the increasing availability of refrigerated foods has contributed to the decline in incidence rates. Recent laboratory data from Japan suggest that oolong tea may contain a substance that can kill stomach cancer cells.

Occupational exposure in coal mining and processing of nickel, rubber, and timber has been reported to increase the risk of gastric carcinoma. Cigarette smoking may also increase the risk, though alcohol exposure does not have a clear relation to risk of gastric cancer.

Helicobacter pylori

Helicobacter pylori, which colonizes approximately half of the world's population, is associated with gastric lymphomas and adenocarcinomas. The overall risk of developing malignancy in the presence of infection is low; however, more than 40% to 50% of gastric cancers are linked with H pylori. The bacterium has been designated as a class I carcinogen. Antibiotics alone can cure localized, node-negative MALT (mucosa-associated lymphoid tissue) lymphomas in about 50% of patients. With regard to gastric adenocarcinoma, H pylori infection is associated with an approximately threefold to fourfold increase in the risk of the disease compared with uninfected controls. Data from Japan and China suggest that H pylori infection can lead to chronic atrophic gastritis. This condition appears to be a major risk factor for gastric cancer.

Intestinal Metaplasia

Intestinal metaplasia, a premalignant lesion, is common in locations where gastric cancer is common and is seen in 80% of resected gastric specimens in Japan.

Individuals With Blood Group A

Individuals with blood group A may have a greater risk of gastric carcinoma than individuals with other blood groups. The risk appears to be for the infiltrative type of gastric carcinoma (rather than the exophytic type).

Gastrectomy

Although reports have suggested that patients undergoing gastric resection for benign disease (usually peptic ulcer disease) are at increased risk of subsequently developing gastric cancer, this association has not been definitely proven. Gastric resection may result in increased gastric pH and subsequent intestinal metaplasia in affected patients.

Pernicious Anemia

Although it has been widely reported that pernicious anemia is associated with the subsequent development of gastric carcinoma, this relationship also has been questioned.

Genetic Abnormalities

The genetic abnormalities associated with gastric cancer are still poorly understood. Abnormalities of the tumor-suppressor gene TP53 (alias p53) are found in over 60% of gastric cancer patients, and abnormalities of the adenomatous polyposis coli (APC) gene are seen in over 50%. The significance of these findings is not clear at present.

Overexpression, amplification, and/or mutations of oncogenes c-Ki-ras, HER2/neu (also known as c-erb-b2), and c-myc most likely play a role in the development of some gastric neoplasms. A high S-phase fraction has been associated with an increased risk of relapse as well.

Interleukin gene polypmorphisms are associated with gastric cancer risk, with some increasing the chances of developing disease and at least one appearing to be protective.

Gastric cancer may be part of several inherited cancer syndromes, including familial adenomatous polyposis, hereditary nonpolyposis colorectal cancer, and Peutz-Jeghers syndrome. Hereditary diffuse gastric cancer occurs due to mutations in the E-cadherin (CDH1) gene. Studies of prophylactic gastrectomy in carriers demonstrate high rates of occult cancers, approximating 80%.

Carriers of mismatch repair gene mutations have an increased risk of developing gastric cancer.

Family History

Family members of a patient with gastric cancer have a twofold to threefold higher risk of stomach cancer than the general population.

Prevention

Recent studies strongly implicate cyclooxygenase 2 (COX-2) in the development of many human cancers, including gastric cancer. Potential mechanisms of oncogenesis include stimulation of tumor angiogenesis, inhibition of apoptosis, immune suppression, and enhancement of invasive potential. Furthermore, COX-2 inhibitors have been shown to decrease the size of gastric adenomas in mice. This information strongly suggests that COX-2 inhibitors may play a role in the prevention, and even treatment, of GI tumors. However, trials with COX-2 inhibitors in other advanced GI malignancies, such as colon cancer, have not been positive, so patients should not be treated with these agents outside the setting of a clinical trial.

Eradication of H pylori should decrease the incidence of gastric cancer by preventing it, and pilot trials assessing this strategy have been undertaken in Central and South America.

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