Gastric Cancer

Gastric cancer is a common cause of cancer-related mortality worldwide.[1] It is particularly common in Japan, South Korea, Chile, and parts of Eastern Europe. More than 70% of cases occur in Asia. In the United States, Black, Asian American, and Hispanic individuals have a higher incidence than other demographic groups.[2]

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. In the US, the 5-year survival rate is approximately 30%.[3]

More than 90% of cases are adenocarcinomas, which are derived from glandular tissue. Gastric tumors are broadly classified as either intestinal or diffuse based on their infiltration patterns. 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 tends to infiltrate with poorly differentiated single cells. It 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.[4]

Risk Factors

Age. Most commonly occurs in people older than 55 years.

Gender. Males have twice the risk of females.

Race/ethnicity. In the US, gastric cancer is 2-3 times more common in Black, Hispanic, and Asian populations.[5]

Socioeconomic status. Lower socioeconomic status is associated with a 2-fold greater risk of distal gastric cancer.[6] However, the risk for proximal gastric cancer is higher in those with a higher socioeconomic status.[7]

Helicobacter pylori infection. This bacterium can cause stomach inflammation and ulcers. Chronic infection with H pylori is a strong risk factor for gastric cancer of the distal stomach and may be responsible for up to 80% of distal gastric cancers.[8] Testing for H pylori infection is widely available, and the infection can be treated with antibiotics and proton pump inhibitors.

Epstein-Barr virus (EBV). Worldwide, it is estimated that about 5-10% of gastric cancers are associated with EBV.[9]

Atrophic gastritis/pernicious anemia. The risk for gastric cancer is increased in individuals with atrophic gastritis. This is true for those with and without pernicious anemia, but individuals with both conditions have an even higher risk.[10]

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, proximal polyposis of the stomach (GAPPS), hereditary breast and ovarian cancer (HBOC), 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, 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.[11]

Smoking and alcohol. It is estimated that 18% of gastric cancer cases can be attributed to smoking. One study found that cancer risk was increased 1.5-fold in smokers.[12] Alcohol consumption also increases risk.[13]

Obesity and overweight. A meta-analysis indicated that excess body weight is associated with an increased risk of gastric cancer.[14] The strength of this association increases with increasing body mass index.

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.[15]

Prior gastric surgery. Patients who have undergone a Billroth procedure (performed for tumor or severe ulcer disease in the distal stomach) have an increased risk for gastric cancer. The Billroth II procedure carries a greater risk than Billroth I. In addition, the risk increases as the interval since surgery increases. The mechanism is unknown, although it may be related to bile salt reflux.[16]

Diet. Factors strongly associated with an increased risk include high intake of salted, smoked, and pickled foods and low intake of fruits and vegetables. (See Nutritional Considerations below.)

Screening

Some countries with a high incidence of gastric cancer, such as Japan, South Korea, Chile, and Venezuela, have implemented population-based screening.[17][18] 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, or familial adenomatous polyposis).[19]

There are no standard or routine tests for stomach cancer; however, selective screening tests may include upper endoscopy, barium-meal gastric photofluorography, and serum pepsinogen levels.

Diagnosis

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 computerized tomography scan and endoscopic ultrasonography.

Treatment

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 role preoperatively in patients with locally advanced disease.

It is also recommended that patients with early gastric cancer receive treatment for Helicobacter pylori infection.

Nutritional Considerations

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 risk factors that were unrelated to refrigeration. Individuals consuming the most foods following 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 with those eating the least. By comparison, individuals following a pattern deemed “prudent” (low in saturated fat, fried foods, and refined carbohydrates and higher in fruits, vegetables, nuts, fiber, and soy foods) were found to reduce the risk for this cancer by 25%, compared with those following less prudent diets.[20]

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 they contain, compared with those who ate the lowest.[21] This relationship does not exist for dietary nitrates, most of which come from vegetables.[22] 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.[23]

Red meat contains particularly high levels of heme iron. In 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 least.[24]

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.[25] 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.[26][27] 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. Also beneficial are 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.[28][29][30][31]

Replacing refined grains with whole grains. Higher intakes of cereal fiber are associated with a roughly 30% lower risk for gastric cancer.[32]

Avoiding highly salted foods. High (compared with low) sodium intakes are associated with a nearly 70% greater risk for gastric cancer.[33]

Maintenance of a healthy body weight. Individuals with a body mass index of 25-29.9 have a more than 20% greater risk for gastric cardia cancer, and individuals with a body mass index ≥ 30 have a more than 80% greater risk compared with normal-weight persons. Obesity was not found to increase the risk for gastric noncardia cancers.[34] (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.[35]

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.[36] Plant-based sources of selenium include Brazil nuts, brown rice, enriched macaroni, sunflower seeds, beans, mushrooms, oatmeal, lentils, spinach, cashews, and bananas.[37]

Low-dose vitamin supplements. Individuals who consume vitamins A, C, or E at levels below the tolerable upper intake level were found to have an almost 25% lower risk when compared with individuals in the lowest supplemental intake group.[38]

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.[39]

Orders

See Basic Diet Orders chapter.

Limit intake of salted and pickled foods.

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 are associated with increased risk of gastric cancer and other cancers. A diet that is very low in animal products (meats, processed meats, dairy, and eggs) and high in fruits, vegetables, and whole grains may reduce that risk, in addition to its other health benefits. Certain foods have properties that reduce gastric cancer risk, such as citrus fruits, cruciferous vegetables (cabbage, broccoli, cauliflower, etc.), and allium vegetables (onions, leeks, and garlic). Reducing the consumption of refined grains, processed foods, and foods high in sodium (e.g., pickles) can also reduce gastric cancer risk. The whole family would do well to incorporate these dietary changes into their lifestyle. Family members living in high-risk areas should consider screening when appropriate.

References

  1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209-249.
  2. Ferlay J, Shin HR, Bray F, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127(12):2893-917.  [PMID:21351269]
  3. National Cancer Institute. Cancer Stat Facts: Stomach Cancer. National Cancer Institute Surveillance, Epidemiology, and End Results Program web site. Accessed March 2, 2023. https://seer.cancer.gov/statfacts/html/stomach.html
  4. Wanebo HJ, Kennedy BJ, Chmiel J, et al. Cancer of the stomach. A patient care study by the American College of Surgeons. Ann Surg. 1993;218(5):583-92.  [PMID:8239772]
  5. Laszkowska M, Tramontano AC, Kim J, et al. Racial and ethnic disparities in mortality from gastric and esophageal adenocarcinoma. Cancer Med. 2020;9(15):5678-5686.  [PMID:32573964]
  6. HAENSZEL W. Variation in incidence of and mortality from stomach cancer, with particular reference to the United States. J Natl Cancer Inst. 1958;21(2):213-62.  [PMID:13576088]
  7. Powell J, McConkey CC. Increasing incidence of adenocarcinoma of the gastric cardia and adjacent sites. Br J Cancer. 1990;62(3):440-3.  [PMID:2206952]
  8. Helicobacter and Cancer Collaborative Group. Gastric cancer and Helicobacter pylori: a combined analysis of 12 case control studies nested within prospective cohorts. Gut. 2001;49(3):347-53.  [PMID:11511555]
  9. Takada K. Epstein-Barr virus and gastric carcinoma. Mol Pathol. 2000;53(5):255-61.  [PMID:11091849]
  10. Brinton LA, Gridley G, Hrubec Z, et al. Cancer risk following pernicious anaemia. Br J Cancer. 1989;59(5):810-3.  [PMID:2736218]
  11. Raj A, Mayberry JF, Podas T. Occupation and gastric cancer. Postgrad Med J. 2003;79(931):252-8.  [PMID:12782770]
  12. González CA, Pera G, Agudo A, et al. Smoking and the risk of gastric cancer in the European Prospective Investigation Into Cancer and Nutrition (EPIC). Int J Cancer. 2003;107(4):629-34.  [PMID:14520702]
  13. Ma K, Baloch Z, He TT, et al. Alcohol Consumption and Gastric Cancer Risk: A Meta-Analysis. Med Sci Monit. 2017;23:238-246.  [PMID:28087989]
  14. Yang P, Zhou Y, Chen B, et al. Overweight, obesity and gastric cancer risk: results from a meta-analysis of cohort studies. Eur J Cancer. 2009;45(16):2867-73.  [PMID:19427197]
  15. Henderson TO, Oeffinger KC, Whitton J, et al. Secondary gastrointestinal cancer in childhood cancer survivors: a cohort study. Ann Intern Med. 2012;156(11):757-66, W-260.  [PMID:22665813]
  16. Takeno S, Hashimoto T, Maki K, et al. Gastric cancer arising from the remnant stomach after distal gastrectomy: a review. World J Gastroenterol. 2014;20(38):13734-40.  [PMID:25320511]
  17. Hamashima C, Shibuya D, Yamazaki H, et al. The Japanese guidelines for gastric cancer screening. Jpn J Clin Oncol. 2008;38(4):259-67.  [PMID:18344316]
  18. Choi IJ. Endoscopic gastric cancer screening and surveillance in high-risk groups. Clin Endosc. 2014;47(6):497-503.  [PMID:25505714]
  19. Hirota WK, Zuckerman MJ, Adler DG, et al. ASGE guideline: the role of endoscopy in the surveillance of premalignant conditions of the upper GI tract. Gastrointest Endosc. 2006;63(4):570-80.  [PMID:16564854]
  20. Bertuccio P, Rosato V, Andreano A, et al. Dietary patterns and gastric cancer risk: a systematic review and meta-analysis. Ann Oncol. 2013;24(6):1450-8.  [PMID:23524862]
  21. Zhu H, Yang X, Zhang C, et al. Red and processed meat intake is associated with higher gastric cancer risk: a meta-analysis of epidemiological observational studies. PLoS One. 2013;8(8):e70955.  [PMID:23967140]
  22. Song P, Wu L, Guan W. Dietary Nitrates, Nitrites, and Nitrosamines Intake and the Risk of Gastric Cancer: A Meta-Analysis. Nutrients. 2015;7(12):9872-95.  [PMID:26633477]
  23. Han J, Jiang Y, Liu X, et al. Dietary Fat Intake and Risk of Gastric Cancer: A Meta-Analysis of Observational Studies. PLoS One. 2015;10(9):e0138580.  [PMID:26402223]
  24. Jakszyn P, Agudo A, Lujan-Barroso L, et al. Dietary intake of heme iron and risk of gastric cancer in the European prospective investigation into cancer and nutrition study. Int J Cancer. 2012;130(11):2654-63.  [PMID:21717452]
  25. Vingeliene S, Chan DS, Aune D, et al. An update of the WCRF/AICR systematic literature review on esophageal and gastric cancers and citrus fruits intake. Cancer Causes Control. 2016;27(7):837-51.  [PMID:27153845]
  26. Wu QJ, Yang Y, Wang J, et al. Cruciferous vegetable consumption and gastric cancer risk: a meta-analysis of epidemiological studies. Cancer Sci. 2013;104(8):1067-73.  [PMID:23679348]
  27. Kim MJ, Kim H. Anticancer Effect of Lycopene in Gastric Carcinogenesis. J Cancer Prev. 2015;20(2):92-6.  [PMID:26151041]
  28. Wu Y, Ye Y, Shi Y, et al. Association between vitamin A, retinol intake and blood retinol level and gastric cancer risk: A meta-analysis. Clin Nutr. 2015;34(4):620-6.  [PMID:25008141]
  29. Woo HD, Kim J. Dietary flavonoid intake and risk of stomach and colorectal cancer. World J Gastroenterol. 2013;19(7):1011-9.  [PMID:23467443]
  30. Fleischauer AT, Poole C, Arab L. Garlic consumption and cancer prevention: meta-analyses of colorectal and stomach cancers. Am J Clin Nutr. 2000;72(4):1047-52.  [PMID:11010950]
  31. Serafini M, Bellocco R, Wolk A, et al. Total antioxidant potential of fruit and vegetables and risk of gastric cancer. Gastroenterology. 2002;123(4):985-91.  [PMID:12360458]
  32. Mendez MA, Pera G, Agudo A, et al. Cereal fiber intake may reduce risk of gastric adenocarcinomas: the EPIC-EURGAST study. Int J Cancer. 2007;121:1618-1623.
  33. D'Elia L, Rossi G, Ippolito R, et al. Habitual salt intake and risk of gastric cancer: a meta-analysis of prospective studies. Clin Nutr. 2012;31(4):489-98.  [PMID:22296873]
  34. Chen Y, Liu L, Wang X, et al. Body mass index and risk of gastric cancer: a meta-analysis of a population with more than ten million from 24 prospective studies. Cancer Epidemiol Biomarkers Prev. 2013;22(8):1395-408.  [PMID:23697611]
  35. Xie Y, Huang S, He T, et al. Coffee consumption and risk of gastric cancer: an updated meta-analysis. Asia Pac J Clin Nutr. 2016;25(3):578-88.  [PMID:27440694]
  36. Cai X, Wang C, Yu W, et al. Selenium Exposure and Cancer Risk: an Updated Meta-analysis and Meta-regression. Sci Rep. 2016;6:19213.  [PMID:26786590]
  37. National Institutes of Health. Selenium. National Institutes of Health Office of Dietary Supplements. Accessed October 6, 2020. https://ods.od.nih.gov/factsheets/Selenium-HealthProfessional/
  38. Kong P, Cai Q, Geng Q, et al. Vitamin intake reduce the risk of gastric cancer: meta-analysis and systematic review of randomized and observational studies. PLoS One. 2014;9(12):e116060.  [PMID:25549091]
  39. Palli D, Russo A, Saieva C, et al. Dietary and familial determinants of 10-year survival among patients with gastric carcinoma. Cancer. 2000;89(6):1205-13.  [PMID:11002214]
Last updated: April 14, 2023