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StomachRobert Kneller, M.D.*
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In the 1930s, stomach cancer was the leading cause of death among U.S. men and the third leading cause among U.S. women after cancers of the uterus and breast (Boring et al., 1991). Since then, the death rates have dropped dramatically--approximately 80 percent among men and 90 percent among women (American Cancer Society, 1991). Today, stomach cancer ranks eighth as a cause of cancer death, and U.S. death rates due to stomach cancer are among the lowest in the world (Boring et al., 1994).
Despite the decrease, stomach cancer is still a major problem. About 24,000 new cases were expected in the United States in 1994 (Boring et al., 1994), and only 18 percent of these patients will live five years after diagnosis (Ries et al., 1994). This represents one of the poorer survival rates for any type of cancer in the U.S., and may be due partly to the fact that the disease usually is not detected until it has spread beyond the stomach (MacDonald et al., 1989). In addition, cancer of the upper portion of the stomach, along with adenocarcinomas of the lower esophagus, recently have become more common, particularly among white men (Blot et al., 1991). Stomach cancer is the leading cause of cancer death in many countries, including Japan and China (Kurihara et al., 1989). Along with lung cancer, it is a leading cause of cancer death worldwide (Parkin et al., 1988). The highest international rates were noted among the Japanese, with world standardized rates for males of more than 70/100,000. Comparable rates for U.S. males were only 10 and 13 percent of the highest worldwide rate for blacks and whites, respectively (Parkin et al., 1992). In most areas of the world, stomach cancer occurs about twice as often among males as females. When persons from regions such as Japan and Eastern Europe migrate to the United States, their stomach cancer rates decrease over successive generations, though lifetime risks approximate most closely those of the country of early childhood (Nomura, 1982). Migrant studies and the marked decrease in death rates in the United States and many other countries suggest that environmental factors play a dominant role. The advent of widespread refrigeration that began in the United States in the 1930s may be partly responsible for the reduced rates (Nomura, 1982). Refrigeration reduced the need for other methods of food preservation and allowed access to fresh fruits and vegetables year round. Surveys have shown that stomach cancer patients eat fewer fresh fruits and vegetables than persons without stomach cancer (Nomura, 1982; Buiatti et al., 1989). Several studies suggest that consumption of allium vegetables (e.g., onions and garlic) and foods rich in carotenes or vitamins C or E are associated with decreased risk of stomach cancer (You et al., 1989; Buiatti, 1989, 1990), while intake of salted, pickled, or smoked foods may increase risk (Nomura, 1982; Buiatti, 1989). Studies in many countries have shown that low socioeconomic status is associated with stomach cancer (Nomura, 1982). A recent study suggests that crowding during early childhood may be related to higher risk among lower socioeconomic classes (Barker et al., 1990). An increased risk of stomach cancer among cigarette smokers has also been detected in several studies (McLaughlin et al., 1990; Kneller, 1991). Stomach cancer is often preceded by a series of changes in the lining of the stomach that occurs over many years. These changes begin with inflammation of the stomach lining (gastritis), then progress to loss of the glandular cells that make up much of the stomach lining (chronic atrophic gastritis), to replacement of these cells by cells resembling those found in the lining of the intestines, to abnormal changes within these intestinal-like cells, and, finally, to the uncontrolled growth of these abnormal cells, signifying cancer (Correa, 1988). N-nitroso compounds (NNCs) may play an important role in inducing these changes (Correa, 1988). While tobacco contains carcinogenic NNCs (Bartsch, 1984), and there are other environmental sources for preformed NNCs (National Academy of Sciences, 1981), the most harmful NNCs are believed to be formed inside the stomach when nitrite combines with nitrogen-containing compounds in foods, prescription drugs, or tobacco smoke (Mirvish, 1983; Bartsch, 1984, 1989). Nitrites are found in a variety of foods, especially pickled or cured foods (National Academy of Sciences, 1981). Nitrites can also be formed from nitrate, which is common in many foods and water supplies (Mirvish, 1983). Vitamins C and E block the formation of NNCs (Mirvish, 1983; Bartsch, 1989), which may explain the protective associations noted above. Other factors may be involved at the cellular level. It has been proposed that infection with Helicobacter pylori, now believed to be a common cause of gastritis and peptic ulcers (Peterson, 1991), may play a role in the initiation of precancerous stomach changes (Correa, 1991). Risk of stomach cancer is increased in patients with pernicious anemia. Pernicious anemia, which is believed to be an immune disorder, results in many of the changes in the stomach lining seen with chronic atrophic gastritis (MacDonald et al., 1989). Studies of atomic bomb survivors and patients treated with X-rays for a spinal disorder indicate that radiation may increase risk (Nomura, 1982). Evidence for a genetic component comes from reports that persons with blood type A, an inherited trait, may be at increased risk for both stomach cancer and pernicious anemia (Nomura, 1982). Family studies suggest a possible genetic susceptibility (Nomura, 1982; Correa, 1988), though it is difficult to distinguish between genetic and environmental influences among persons who have shared the same environment. For the general population, a diet rich in fresh fruits and vegetables may reduce risk, as might limiting tobacco use and consumption of pickled, smoked, or heavily salted foods. |
* From the Fogarty International Center, National Institutes of Health, Bethesda, Maryland
