Gastric cancer is the second most common cause of cancer-related mortality worldwide. Incidence varies greatly by geographic area and race. Areas of highest incidence include Japan, Korea, Chile, and parts of Eastern Europe. Seventy-three percent of gastric cancer occurs in Asia, with 50% diagnosed in China alone. In United States, it is the 15th most common type of cancer, and African Americans, Asian Americans, and Hispanics have a higher incidence than other demographic groups.
Prevalence has been decreasing over the last century, likely due to better methods of food preservation, improved sanitation, and lower infectious disease rates. In addition, improved screening techniques—especially in Japan and other high-risk areas—have led to a decrease in mortality. Nonetheless, gastric cancer remains one of the most lethal malignancies, with the 5-year survival rate in the United States less than 20%.
More than 90% of cases are adenocarcinomas, which are derived from glandular tissue. Tumors are classified as either intestinal or diffuse. In the intestinal type, which is far more common, tumors grow as discrete masses and eventually erode through the stomach wall into nearby organs. The diffuse type is less common overall, but is more prevalent in younger patients and carries a poorer prognosis. Diffuse tumors are poorly differentiated cancers with little cell cohesion. As a result, they grow outward along the submucosa of the stomach, widely enveloping the stomach without producing a discrete mass.
Tumors tend to be asymptomatic until the disease is advanced. The most common symptoms of advanced tumors are weight loss, early satiety, abdominal pain, nausea, and vomiting. Less common symptoms include dysphagia, melena, a palpable abdominal mass, and ascites.
Age. The disease is rare before age 40, and the incidence increases steadily thereafter.
Gender. Males have twice the risk of females.
Socioeconomic status: Lower socioeconomic status is associated with a two-fold greater risk of distal gastric cancer . However the risk for proximal gastric cancer is higher in those with a higher socioeconomic status.
Helicobacter pylori infection: Chronic infection is a strong risk factor for gastric cancer of the distal stomach and may be responsible for up to 80% of distal gastric cancers.
Epstein-Barr virus (EBV): Worldwide, it is estimated that about 5%-10% of gastric cancers are associated with EBV.
Atrophic gastritis/pernicious anemia: The risk for gastric cancer is increased in individuals with atrophic gastritis with and without pernicious anemia; those who have both conditions have an even higher risk.
Genetics: There is a slightly increased risk of gastric cancer in individuals who have a family history of gastric cancer. There are some rare forms of truly hereditary gastric cancer, such as hereditary diffuse gastric cancer (HDGC), gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS), and familial intestinal gastric cancer (FIGC).
The risk for gastric cancer is also increased in a number of hereditary cancer syndromes, such as Lynch syndrome, familial adenomatous polyposis (FAP), and, Peutz Jeghers syndrome.
Environmental exposures: There is some evidence that occupational exposures in rubber manufacturing, tin and coal mining and steel and iron processing may increase the risk of gastric cancer.
Smoking: It is estimated that 18% of gastric cancer can be attributed to smoking. One study found that cancer risk was increased 1.53 fold in smokers.
Obesity and overweight: Having a BMI ≥ 25 increases the risk of gastric cancer.
Abdominal radiation: Individuals who received radiation as part of cancer treatment, e.g., for testicular cancer, Hodgkin’s lymphoma, or childhood cancers, have a greater risk for gastric cancer.
Prior gastric surgery: Patients who have undergone a Billroth procedure have an increased risk for gastric cancer. The Billroth II procedure carries a greater risk that the Billroth I and the risk increases as the interval since surgery increases. The mechanism is unknown, although it may be related to bile salt reflux.
Diet. Factors strongly associated with an increased risk include high intake of salted, smoked, and pickled foods, and low intake of fruits and vegetables. Conclusive evidence for the role of alcohol has yet to be demonstrated. However, the concomitant use of alcohol and tobacco appears to increase the risk of gastric cancer more than use of tobacco alone. (See Nutritional Considerations below.)
Some countries with a high incidence of gastric cancer, such as Japan, Korea, Chile and Venezuela, have implemented population based screening. , In populations with a low incidence, selective screening is recommended for high-risk individuals, for example, those with pernicious anemia or a hereditary syndrome that carries a predisposition to gastric cancer (e.g., Lynch syndrome, Peutz-Jeghers syndrome, familial adenomatous polyposis).
The two main screening tests used for gastric cancer screening are upper endoscopy and contrast radiography.
The tissue diagnosis of gastric cancer is typically made with a biopsy during upper endoscopy. The TNM (Tumor, Node, Metastasis) classification is the preferred system for tumor staging, once a diagnosis is made and is usually done with abdominopelvic CT scan and endoscopic ultrasonography.
Complete surgical resection offers the only hope for cure. Patients with gastric cancer and positive lymph nodes are usually treated with radical gastrectomy. Some patients with early disease and without lymph node involvement may be treated with endoscopic resection. The treatment of more advanced disease may also include adjuvant chemotherapy and/ or radiation. Neoadjuvant chemotherapy may play a row perioperatively in patients with locally advanced disease.
It is also recommended that patients with early gastric cancer receive treatment for Helicobacter pylori infection.
During the early 20th century, stomach cancer incidence consistently declined in countries where refrigeration supplanted other methods of food preservation. In the latter part of the 20th century and early 21st century, several dietary factors emerged as gastric cancer risk factors that were unrelated to refrigeration. Individuals consuming the most foods on a Western dietary pattern (including meat, eggs, high fat dairy foods and refined carbohydrates) were found to have a 50% higher risk for gastric cancer, compared to those eating the least. By comparison, individuals eating closest to a ‘Prudent’ pattern (low in saturated fat, fried foods, refined carbohydrates and higher in fruits, vegetables, nuts, fiber and soy foods) were found to reduce the risk for this cancer by 25%, compared to those eating the fewest. The following dietary factors are also associated with reduced risk:
Avoidance of animal products, particularly those containing nitrites. Studies have found a 45% greater risk in individuals who eat the highest amount of red and processed meats and the nitrite food preservatives these contain, compared with those who ate the least. This relationship does not exist for dietary nitrates, most of which come from vegetables. Higher intakes of saturated fat are associated with a roughly 30% higher risk for gastric cancer as well. In contrast, vegetable fats are associated with a significantly lower risk.
Red meat contains particularly high levels of heme iron. In the the European prospective investigation into cancer and nutrition (EURGAST-EPIC) study, individuals consuming the most heme iron had a 13% higher risk for gastric cancer), compared with those consuming the lowest amount.
Eating more fruits and vegetables. Consumption of certain fruits and vegetables may be particularly effective for reducing gastric cancer risk. Persons consuming the most citrus fruits have an almost 40% lower risk for gastric cardia cancers when compared with those eating the least. Consumption of higher (compared with lower) amounts of cruciferous vegetables is associated with a roughly 20% lower risk for this cancer and high intakes or serum levels of lycopene have also been associated with a significantly lower risk for gastric cancer. Some of the active principles that have been suggested for the apparent anticancer effects of fruits and vegetables include vitamin C and other antioxidants (due to their inhibiting effects on nitrosamine formation); vitamin A, flavonoids, and sulfur compounds in Allium species of vegetables, including garlic and onion; and the total antioxidant potential of the diet, particularly in H pylori-infected persons.
Replacing refined grains with whole grains. Higher intakes of cereal fiber are associated with a roughly 30% lower risk for gastric cancer.
Avoiding highly salted foods. High (compared with low) sodium intakes are associated with a nearly 70% greater risk for gastric cancer.
Maintenance of a healthy body weight. Individuals who are overweight have a more than 20% greater risk for gastric cardia cancer, and obese individuals have a greater than 80% greater risk compared with normal-weight persons. Obesity was however not found to increase the risk for gastric non-cardia cancers. (See Obesity chapter.)
Coffee consumption. Coffee drinkers have a 7%-12% lower risk for gastric cancer when compared with those drinking little or no coffee.
Higher intakes of dietary selenium. Individuals who have higher serum or tissue levels of selenium have a roughly 15% lower cancer risk, compared with those having the lowest levels. Selenium supplements do not contribute to this risk reduction. Good sources of selenium include Brazil nuts, brown rice, and macaroni.
Low dose vitamin supplements. Individuals who consume vitamins A, C, or E at levels below the tolerable upper intake (UL) level were found to have an almost 25% lower risk when compared with individuals in the lowest supplemental intake group.
Diet and survival in gastric cancer. Although the role of diet in gastric cancer prognosis needs further study, data indicate that patients whose diets were lower in animal fat, animal protein, and nitrosamines before diagnosis had approximately half the risk of death from this cancer, compared with other patients.
Limit intake of salted and pickled foods.
Avoid foods preserved with nitrates.
What to Tell the Family
Diet plays an important role in the prevention of gastric cancer, which remains one of the leading causes of cancer-related death worldwide. Animal products, especially those preserved with nitrates, are associated with increased risk of gastric cancer and other cancers. A diet that includes regular servings of fruits, vegetables, and whole grains may reduce that risk, in addition to its other health benefits. The whole family would do well to incorporate these dietary changes into their lifestyle. Also, family members that live in high risk areas should consider routine screening, when appropriate.
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