Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Global burden of gastric cancer: epidemiological trends, risk factors, screening and prevention

Nature Reviews Clinical Oncology volume 20, pages 338–349 (2023)Cite this article

Subjects

Abstract

Gastric cancer remains a major cause of cancer-related mortality worldwide. The temporal trends for this malignancy, however, are dynamic, and reports from the past decade indicate important declines in some regions and demographic groups, as well as a few notable exceptions in which gastric cancer rates are either stable or increasing. Two main anatomical subtypes of gastric cancer exist, non-cardia and cardia, with different temporal trends and risk factors (such as obesity and reflux for cardia gastric cancer and Helicobacter pylori infection for non-cardia gastric cancer). Shifts in the distribution of anatomical locations have been detected in several high-incidence regions. H. pylori is an important aetiological factor for gastric cancer; importantly, the anticipated long-term findings from studies examining the effect of H. pylori eradication on the risk of (re)developing gastric cancer have emerged in the past few years. In this Review, we highlight the latest trends in incidence and mortality using an evidence-based approach. We make the best possible inferences, including clinical and public health inference, on the basis of the quality of the evidence available, and highlight burning questions as well as gaps in knowledge and public health practice that need to be addressed to reduce gastric cancer burden worldwide.

Key points

  • Globally, gastric cancer remains the fifth most common malignant cancer and the fourth leading cause of cancer-related mortality. Despite declining incidence rates, the global burden of this malignancy is expected to have a 62% increase by 2040.

  • Overall, gastric cancer incidence rates have been decreasing over the past 5 decades in the USA, although the incidence of non-cardia gastric cancer among adults aged <50 years and that of advanced-stage gastric cancer in Hispanic individuals are both increasing.

  • Worldwide, Helicobacter pylori infection accounts for almost 90% of distal gastric cancers; other well-established risk factors include excess body fat, cigarette smoking and diets high in salt and processed meats.

  • Other possible risk factors for gastric cancer include Epstein–Barr virus infection, autoimmune gastritis and Ménétrier disease, and possible protective factors include high vegetable intake and treatment with nonsteroidal anti-inflammatory drugs and statins.

  • A small proportion of all gastric cancers are diagnosed in patients not infected with H. pylori; other components of the gastric microbiome might have a role in the development of these cancers.

  • Population-based screening and surveillance programmes and H. pylori eradication hold promise for reducing gastric cancer-related mortality.

  • The knowledge on risk factors needs to be translated into actionable diagnostic algorithms for public health and clinical use.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Get just this article for as long as you need it

$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Worldwide gastric cancer incidence in 2020.
Fig. 2: Worldwide gastric cancer mortality in 2020.
Fig. 3: Gastric cancer incidence in the USA 1975–2019.
Fig. 4: Gastric cancer survival in the USA 2000–2014.

References

  1. Sung, H. et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 71, 209–249 (2021).

    Article  PubMed  Google Scholar 

  2. Lauren, P. The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. an attempt at a histo-clinical classification. Acta Pathol. Microbiol. Scand. 64, 31–49 (1965).

    Article  CAS  PubMed  Google Scholar 

  3. Hansford, S. et al. Hereditary diffuse gastric cancer syndrome: CDH1 mutations and beyond. JAMA Oncol. 1, 23–32 (2015).

    Article  PubMed  Google Scholar 

  4. Correa, P. et al. A model for gastric cancer epidemiology. Lancet 2, 58–60 (1975).

    Article  CAS  PubMed  Google Scholar 

  5. Correa, P. Gastric cancer: overview. Gastroenterol. Clin. North Am. 42, 211–217 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  6. Fock, K. M. Review article: the epidemiology and prevention of gastric cancer. Aliment. Pharmacol. Ther. 40, 250–260 (2014).

    Article  CAS  PubMed  Google Scholar 

  7. Arnold, M. et al. Is gastric cancer becoming a rare disease? A global assessment of predicted incidence trends to 2035. Gut 69, 823–829 (2020).

    Article  PubMed  Google Scholar 

  8. Lin, Y. et al. Global patterns and trends in gastric cancer incidence rates (1988–2012) and predictions to 2030. Gastroenterology 161, 116–127.e8 (2021).

    Article  PubMed  Google Scholar 

  9. Morgan, E. et al. The current and future incidence and mortality of gastric cancer in 185 countries, 2020–40: a population-based modelling study. EClinicalMedicine 47, 101404 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  10. Hooi, J. K. Y. et al. Global prevalence of Helicobacter pylori infection: systematic review and meta-analysis. Gastroenterology 153, 420–429 (2017).

    Article  PubMed  Google Scholar 

  11. Ferlay J, et al. Global Cancer Observatory: Cancer Today (International Agency for Research on Cancer, 2020).

  12. Thrift, A. P. & El-Serag, H. B. Burden of gastric cancer. Clin. Gastroenterol. Hepatol. 18, 534–542 (2020).

    Article  PubMed  Google Scholar 

  13. Wang, Z. et al. Incidence of gastric cancer in the USA during 1999 to 2013: a 50-state analysis. Int. J. Epidemiol. 47, 966–975 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  14. Thrift, A. P. & Nguyen, T. H. Gastric cancer epidemiology. Gastrointest. Endosc. Clin. N. Am. 31, 425–439 (2021).

    Article  PubMed  Google Scholar 

  15. Anderson, W. F. et al. Age-specific trends in incidence of noncardia gastric cancer in US adults. JAMA 303, 1723–1728 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. SEER. Surveillance, Epidemiology, and End Results (SEER) Program (www.seer.cancer.gov) SEER*Stat Database: Incidence – SEER Research Data, 8 Registries, Nov 2021 Sub (1975–2019) – Linked To County Attributes – Time Dependent (1990–2019) Income/Rurality, 1969–2020 Counties, National Cancer Institute, DCCPS, Surveillance Research Program, released April 2022, based on the November 2021 submission (2022).

  17. Wang, Z., El-Serag, H. B. & Thrift, A. P. Increasing incidence of advanced non-cardia gastric cancers among younger Hispanics in the USA. Dig. Dis. Sci. 66, 1669–1672 (2021).

    Article  PubMed  Google Scholar 

  18. SEER. Surveillance, Epidemiology, and End Results (SEER) Program (www.seer.cancer.gov) SEER*Stat Database: Incidence - SEER Research Data, 17 Registries, Nov 2021 Sub (2000–2019) – Linked To County Attributes – Time Dependent (1990–2019) Income/Rurality, 1969–2020 Counties, National Cancer Institute, DCCPS, Surveillance Research Program, released April 2022, based on the November 2021 submission (2022).

  19. IARC Working Group on the Evaluation of Carcinogenic Risk to Humans. Schistosomes, Liver Flukes and Helicobacter pylori (IARC Monographs on the Evaluation of Carcinogenic Risks to Humans vol. 61) (IARC, 1994).

  20. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Biological Agents (IARC Monographs on the Evaluation of Carcinogenic Risks to Humans vol. 100B) (IARC, 2012).

  21. Gonzalez, C. A. et al. Helicobacter pylori infection assessed by ELISA and by immunoblot and noncardia gastric cancer risk in a prospective study: the Eurgast-EPIC project. Ann. Oncol. 23, 1320–1324 (2012).

    Article  CAS  PubMed  Google Scholar 

  22. Lochhead, P. & El-Omar, E. M. Helicobacter pylori infection and gastric cancer. Best Pract. Res. Clin. Gastroenterol. 21, 281–297 (2007).

    Article  CAS  PubMed  Google Scholar 

  23. Plummer, M. et al. Global burden of gastric cancer attributable to Helicobacter pylori. Int. J. Cancer 136, 487–490 (2015).

    Article  CAS  PubMed  Google Scholar 

  24. Parsonnet, J. et al. Helicobacter pylori infection in intestinal- and diffuse-type gastric adenocarcinomas. J. Natl. Cancer Inst. 83, 640–643 (1991).

    Article  CAS  PubMed  Google Scholar 

  25. Hansson, L. R. et al. Prevalence of Helicobacter pylori infection in subtypes of gastric cancer. Gastroenterology 109, 885–888 (1995).

    Article  CAS  PubMed  Google Scholar 

  26. Zamani, M. et al. Systematic review with meta-analysis: the worldwide prevalence of Helicobacter pylori infection. Aliment. Pharmacol. Ther. 47, 868–876 (2018).

    Article  CAS  PubMed  Google Scholar 

  27. Peleteiro, B. et al. Prevalence of Helicobacter pylori infection worldwide: a systematic review of studies with national coverage. Dig. Dis. Sci. 59, 1698–1709 (2014).

    Article  PubMed  Google Scholar 

  28. Lu, Y. et al. Prevalence of Helicobacter pylori in non-cardia gastric cancer in China: a systematic review and meta-analysis. Front. Oncol. 12, 850389 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  29. Ricci, C., Holton, J. & Vaira, D. Diagnosis of Helicobacter pylori: invasive and non-invasive tests. Best Pract. Res. Clin. Gastroenterol. 21, 299–313 (2007).

    Article  PubMed  Google Scholar 

  30. McNulty, C. et al. Test and treat for dyspepsia–but which test? BMJ 330, 105–106 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  31. Vaira, D. & Vakil, N. Blood, urine, stool, breath, money, and Helicobacter pylori. Gut 48, 287–289 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Simán, J. H. et al. Helicobacter pylori and CagA seropositivity and its association with gastric and oesophageal carcinoma. Scand. J. Gastroenterol. 42, 933–940 (2007).

    Article  PubMed  Google Scholar 

  33. Simán, J. H. et al. Association between Helicobacter pylori and gastric carcinoma in the city of Malmö, Sweden. A prospective study. Scand. J. Gastroenterol. 32, 1215–1221 (1997).

    Article  PubMed  Google Scholar 

  34. Mitchell, H. et al. Immunoblotting using multiple antigens is essential to demonstrate the true risk of Helicobacter pylori infection for gastric cancer. Aliment. Pharmacol. Ther. 28, 903–910 (2008).

    CAS  PubMed  Google Scholar 

  35. Morais, S. et al. “True” Helicobacter pylori infection and non-cardia gastric cancer: a pooled analysis within the Stomach cancer Pooling (StoP) Project. Helicobacter 27, e12883 (2022).

    Article  CAS  PubMed  Google Scholar 

  36. Pormohammad, A. et al. Global estimate of gastric cancer in Helicobacter pylori-infected population: a systematic review and meta-analysis. J. Cell Physiol. 234, 1208–1218 (2019).

    Article  CAS  PubMed  Google Scholar 

  37. Testoni, P. A. et al. Gastric cancer in chronic atrophic gastritis. Associated gastric ulcer adds no further risk. J. Clin. Gastroenterol. 9, 298–302 (1987).

    Article  CAS  PubMed  Google Scholar 

  38. Uemura, N. et al. Helicobacter pylori infection and the development of gastric cancer. N. Engl. J. Med. 345, 784–789 (2001).

    Article  CAS  PubMed  Google Scholar 

  39. Suzuki, G. et al. Low-positive antibody titer against Helicobacter pylori cytotoxin-associated gene A (CagA) may predict future gastric cancer better than simple seropositivity against H. pylori CagA or against H. pylori. Cancer Epidemiol. Biomark. Prev. 16, 1224–1228 (2007).

    Article  CAS  Google Scholar 

  40. Higashi, H. et al. Biological activity of the Helicobacter pylori virulence factor CagA is determined by variation in the tyrosine phosphorylation sites. Proc. Natl. Acad. Sci. USA 99, 14428–14433 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Hayashi, T. et al. Differential mechanisms for SHP2 binding and activation are exploited by geographically distinct Helicobacter pylori CagA oncoproteins. Cell Rep. 20, 2876–2890 (2017).

    Article  CAS  PubMed  Google Scholar 

  42. Tatemichi, M. et al. Ethnic difference in serology of Helicobacter pylori CagA between Japanese and non-Japanese Brazilians for non-cardia gastric cancer. Cancer Sci. 94, 64–69 (2003).

    Article  CAS  PubMed  Google Scholar 

  43. El Hafa, F. et al. Association between Helicobacter pylori antibodies determined by multiplex serology and gastric cancer risk: a meta-analysis. Helicobacter 27, e12881 (2022).

    Article  CAS  PubMed  Google Scholar 

  44. Kpoghomou, M. A. et al. Association of Helicobacter pylori babA2 gene and gastric cancer risk: a meta-analysis. BMC Cancer 20, 465 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Ma, J. et al. Associations between cytokine gene polymorphisms and susceptibility to Helicobacter pylori infection and Helicobacter pylori related gastric cancer, peptic ulcer disease: a meta-analysis. PLoS ONE 12, e0176463 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  46. van der Kaaij, R. T. et al. A population-based study on intestinal and diffuse type adenocarcinoma of the oesophagus and stomach in the Netherlands between 1989 and 2015. Eur. J. Cancer 130, 23–31 (2020).

    Article  PubMed  Google Scholar 

  47. Wachtel, M. S. et al. Different regression equations relate age to the incidence of Lauren types 1 and 2 stomach cancer in the SEER database: these equations are unaffected by sex or race. BMC Cancer 6, 65 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  48. Yao, Q., Qi, X. & Xie, S. H. Sex difference in the incidence of cardia and non-cardia gastric cancer in the United States, 1992–2014. BMC Gastroenterol. 20, 418 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  49. Karimi, P. et al. Gastric cancer: descriptive epidemiology, risk factors, screening, and prevention. Cancer Epidemiol. Biomark. Prev. 23, 700–713 (2014).

    Article  Google Scholar 

  50. IARC Working Group on the Evaluation of Carcinogenic Risk to Humans. Tobacco Smoke and Involuntary Smoking (IARC Monographs on the Evaluation of Carcinogenic Risk to Humans vol. 83) (IARC, 2004).

  51. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Ingested Nitrate and Nitrite, and Cyanobacterial Peptide Toxins (IARC Monographs on the Evaluation of Carcinogenic Risks to Humans vol. 94) (IARC, 2010).

  52. Ladeiras-Lopes, R. et al. Smoking and gastric cancer: systematic review and meta-analysis of cohort studies. Cancer Causes Control 19, 689–701 (2008).

    Article  PubMed  Google Scholar 

  53. Praud, D. et al. Cigarette smoking and gastric cancer in the Stomach cancer Pooling (StoP) Project. Eur. J. Cancer Prev. 27, 124–133 (2018).

    Article  PubMed  Google Scholar 

  54. Sasazuki, S., Sasaki, S. & Tsugane, S. Cigarette smoking, alcohol consumption and subsequent gastric cancer risk by subsite and histologic type. Int. J. Cancer 101, 560–566 (2002).

    Article  CAS  PubMed  Google Scholar 

  55. Pelucchi, C. et al. The Stomach cancer Pooling (StoP) Project: study design and presentation. Eur. J. Cancer Prev. 24, 16–23 (2015).

    Article  PubMed  Google Scholar 

  56. Li, W. Y. et al. Smoking status and subsequent gastric cancer risk in men compared with women: a meta-analysis of prospective observational studies. BMC Cancer 19, 377 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  57. Sadjadi, A. et al. Neglected role of hookah and opium in gastric carcinogenesis: a cohort study on risk factors and attributable fractions. Int. J. Cancer 134, 181–188 (2014).

    Article  PubMed  Google Scholar 

  58. Chen, Y. 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. Biomark. Prev. 22, 1395–1408 (2013).

    Article  Google Scholar 

  59. Yang, P. et al. Overweight, obesity and gastric cancer risk: results from a meta-analysis of cohort studies. Eur. J. Cancer 45, 2867–2873 (2009).

    Article  PubMed  Google Scholar 

  60. Bae, J. M. Body mass index and risk of gastric cancer in Asian adults: a meta-epidemiological meta-analysis of population-based cohort studies. Cancer Res. Treat. 52, 369–373 (2020).

    Article  PubMed  Google Scholar 

  61. Jang, J. et al. Association between body mass index and risk of gastric cancer by anatomical and histological subtypes in over 500,000 East and Southeast Asian cohort participants. Cancer Epidemiol. Biomark. Prev. 31, 1727–1734 (2022).

    Article  Google Scholar 

  62. Zheng, J. et al. Haemoglobin A1c and serum glucose levels and risk of gastric cancer: a systematic review and meta-analysis. Br. J. Cancer 126, 1100–1107 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Dabo, B. et al. The association between diabetes and gastric cancer: results from the Stomach cancer Pooling Project consortium. Eur. J. Cancer Prev. 31, 260–269 (2022).

    Article  PubMed  Google Scholar 

  64. Zhao, Z., Yin, Z. & Zhao, Q. Red and processed meat consumption and gastric cancer risk: a systematic review and meta-analysis. Oncotarget 8, 30563–30575 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  65. Kim, S. R. et al. Effect of red, processed, and white meat consumption on the risk of gastric cancer: an overall and dose-response meta-analysis. Nutrients 11, 826 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  66. Harrison, L. E. et al. The role of dietary factors in the intestinal and diffuse histologic subtypes of gastric adenocarcinoma: a case–control study in the U.S.Cancer 80, 1021–1028 (1997).

    Article  CAS  PubMed  Google Scholar 

  67. Tricker, A. R. & Preussmann, R. Carcinogenic N-nitrosamines in the diet: occurrence, formation, mechanisms and carcinogenic potential. Mutat. Res. 259, 277–289 (1991).

    Article  CAS  PubMed  Google Scholar 

  68. Song, P., Wu, L. & Guan, W. Dietary nitrates, nitrites, and nitrosamines intake and the risk of gastric cancer: a meta-analysis. Nutrients 7, 9872–9895 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Fox, J. G. et al. High-salt diet induces gastric epithelial hyperplasia and parietal cell loss, and enhances Helicobacter pylori colonization in C57BL/6 mice. Cancer Res. 59, 4823–4828 (1999).

    CAS  PubMed  Google Scholar 

  70. D’Elia, L. et al. Habitual salt intake and risk of gastric cancer: a meta-analysis of prospective studies. Clin. Nutr. 31, 489–498 (2012).

    Article  PubMed  Google Scholar 

  71. Peleteiro, B. et al. Salt intake and gastric cancer risk according to Helicobacter pylori infection, smoking, tumour site and histological type. Br. J. Cancer 104, 198–207 (2011).

    Article  CAS  PubMed  Google Scholar 

  72. Firestone, M. J. et al. Asian American dietary sources of sodium and salt behaviors compared with other racial/ethnic groups, NHANES, 2011–2012. Ethn. Dis. 27, 241–248 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  73. Morais, S. et al. Salt intake and gastric cancer: a pooled analysis within the Stomach cancer Pooling (StoP) Project. Cancer Causes Control 33, 779–791 (2022).

    Article  PubMed  Google Scholar 

  74. Toyoda, T. et al. Synergistic upregulation of inducible nitric oxide synthase and cyclooxygenase-2 in gastric mucosa of Mongolian gerbils by a high-salt diet and Helicobacter pylori infection. Histol. Histopathol. 23, 593–599 (2008).

    CAS  PubMed  Google Scholar 

  75. Loh, J. T., Torres, V. J. & Cover, T. L. Regulation of Helicobacter pylori cagA expression in response to salt. Cancer Res. 67, 4709–4715 (2007).

    Article  CAS  PubMed  Google Scholar 

  76. World Cancer Research Fund/American Institute for Cancer Research. Food, Nutrition, Physical Activity, and the Prevention of Cancer: a Global Perspective (AICR, 2007).

  77. Fang, X. et al. Landscape of dietary factors associated with risk of gastric cancer: a systematic review and dose-response meta-analysis of prospective cohort studies. Eur. J. Cancer 51, 2820–2832 (2015).

    Article  PubMed  Google Scholar 

  78. Kobayashi, M. et al. Vegetables, fruit and risk of gastric cancer in Japan: a 10-year follow-up of the JPHC Study Cohort I. Int. J. Cancer 102, 39–44 (2002).

    Article  CAS  PubMed  Google Scholar 

  79. Rota, M. et al. Education and gastric cancer risk-an individual participant data meta-analysis in the StoP Pproject consortium. Int. J. Cancer 146, 671–681 (2020).

    Article  CAS  PubMed  Google Scholar 

  80. Alicandro, G. et al. The mediating role of combined lifestyle factors on the relationship between education and gastric cancer in the Stomach cancer Pooling (StoP) Project. Br. J. Cancer 146, 855–681 (2022).

    Article  Google Scholar 

  81. Miao, P. & Guan, L. Association of dietary cholesterol intake with risk of gastric cancer: a systematic review and meta-analysis of observational studies. Front. Nutr. 8, 722450 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  82. Guo, Y. et al. Dairy consumption and gastric cancer risk: a meta-analysis of epidemiological studies. Nutr. Cancer 67, 555–568 (2015).

    Article  CAS  PubMed  Google Scholar 

  83. Martimianaki, G. et al. Tea consumption and gastric cancer: a pooled analysis from the Stomach cancer Pooling (StoP) Project consortium. Br. J. Cancer 127, 726–734 (2022).

    Article  PubMed  Google Scholar 

  84. Lazarević, K., Nagorni, A. & Jeremić, M. Carbohydrate intake, glycemic index, glycemic load and risk of gastric cancer. Cent. Eur. J. Public. Health 17, 75–78 (2009).

    Article  PubMed  Google Scholar 

  85. Du, Y. et al. Chili consumption and risk of gastric cancer: a meta-analysis. Nutr. Cancer 73, 45–54 (2021).

    Article  CAS  PubMed  Google Scholar 

  86. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Personal Habits and Indoor Combustions (IARC Monographs on the Evaluation of Carcinogenic Risks to Humans vol. 100E) (IARC, 2012).

  87. Na, H.-K. & Lee, J. Y. Molecular basis of alcohol-related gastric and colon cancer. Int. J. Mol. Sci. 18, 1116 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  88. Jelski, W. et al. Alcohol dehydrogenase (ADH) isoenzymes and aldehyde dehydrogenase (ALDH) activity in the sera of patients with gastric cancer. Dig. Dis. Sci. 53, 2101–2105 (2008).

    Article  CAS  PubMed  Google Scholar 

  89. Deng, W. et al. Alcohol consumption and risk of stomach cancer: a meta-analysis. Chem. Biol. Interact. 336, 109365 (2021).

    Article  CAS  PubMed  Google Scholar 

  90. Wang, P. L. et al. Alcohol drinking and gastric cancer risk: a meta-analysis of observational studies. Oncotarget 8, 99013–99023 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  91. Rota, M. et al. Alcohol consumption and gastric cancer risk — a pooled analysis within the StoP project consortium. Int. J. Cancer 141, 1950–1962 (2017).

    Article  CAS  PubMed  Google Scholar 

  92. Lim, H. Y. et al. Increased expression of cyclooxygenase-2 protein in human gastric carcinoma. Clin. Cancer Res. 6, 519–525 (2000).

    CAS  PubMed  Google Scholar 

  93. Oba, M. et al. Chemoprevention of glandular stomach carcinogenesis through duodenogastric reflux in rats by a COX-2 inhibitor. Int. J. Cancer 123, 1491–1498 (2008).

    Article  CAS  PubMed  Google Scholar 

  94. Huang, X. Z. et al. Aspirin and non-steroidal anti-inflammatory drugs use reduce gastric cancer risk: a dose-response meta-analysis. Oncotarget 8, 4781–4795 (2017).

    Article  PubMed  Google Scholar 

  95. Epplein, M. et al. Nonsteroidal antiinflammatory drugs and risk of gastric adenocarcinoma: the multiethnic cohort study. Am. J. Epidemiol. 170, 507–514 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  96. Follet, J. et al. The association of statins and taxanes: an efficient combination trigger of cancer cell apoptosis. Br. J. Cancer 106, 685–692 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Singh, P. P. & Singh, S. Statins are associated with reduced risk of gastric cancer: a systematic review and meta-analysis. Ann. Oncol. 24, 1721–1730 (2013).

    Article  CAS  PubMed  Google Scholar 

  98. Wu, X. D. et al. Statins are associated with reduced risk of gastric cancer: a meta-analysis. Eur. J. Clin. Pharmacol. 69, 1855–1860 (2013).

    Article  CAS  PubMed  Google Scholar 

  99. MacArthur, T. A. et al. Association of common medications and the risk of early-onset gastric cancer: a population-based matched study. J. Cancer Epidemiol. 2021, 2670502 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  100. Segna, D. et al. Association between proton-pump inhibitors and the risk of gastric cancer: a systematic review with meta-analysis. Ther. Adv. Gastroenterol. 14, 17562848211051463 (2021).

    Article  CAS  Google Scholar 

  101. Gonzalez, C. A. & Agudo, A. Carcinogenesis, prevention and early detection of gastric cancer: where we are and where we should go. Int. J. Cancer 130, 745–753 (2012).

    Article  CAS  PubMed  Google Scholar 

  102. Gullo, I., van der Post, R. S. & Carneiro, F. Recent advances in the pathology of heritable gastric cancer syndromes. Histopathology 78, 125–147 (2021).

    Article  PubMed  Google Scholar 

  103. Blair, V. R. et al. Hereditary diffuse gastric cancer: updated clinical practice guidelines. Lancet Oncol. 21, e386–e397 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Li, J. et al. Point mutations in exon 1B of APC reveal gastric adenocarcinoma and proximal polyposis of the stomach as a familial adenomatous polyposis variant. Am. J. Hum. Genet. 98, 830–842 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Vogelaar, I. P. et al. Gastric cancer in three relatives of a patient with a biallelic IL12RB1 mutation. Fam. Cancer 14, 89–94 (2015).

    Article  CAS  PubMed  Google Scholar 

  106. Capelle, L. G. et al. Risk and epidemiological time trends of gastric cancer in Lynch syndrome carriers in the Netherlands. Gastroenterology 138, 487–492 (2010).

    Article  PubMed  Google Scholar 

  107. Oliveira, C., Seruca, R. & Carneiro, F. Genetics, pathology, and clinics of familial gastric cancer. Int. J. Surg. Pathol. 14, 21–33 (2006).

    Article  CAS  PubMed  Google Scholar 

  108. Camargo, M. C. et al. Determinants of Epstein–Barr virus-positive gastric cancer: an international pooled analysis. Br. J. Cancer 105, 38–43 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Bizzaro, N. & Antico, A. Diagnosis and classification of pernicious anemia. Autoimmun. Rev. 13, 565–568 (2014).

    Article  PubMed  Google Scholar 

  110. Weis, V. G. & Goldenring, J. R. Current understanding of SPEM and its standing in the preneoplastic process. Gastric Cancer 12, 189–197 (2009).

    Article  PubMed  Google Scholar 

  111. Zamcheck, N. et al. Occurrence of gastric cancer among patients with pernicious anemia at the Boston City Hospital. N. Engl. J. Med. 252, 1103–1110 (1955).

    Article  CAS  PubMed  Google Scholar 

  112. Li, D. et al. Risks and predictors of gastric adenocarcinoma in patients with gastric intestinal metaplasia and dysplasia: a population-based study. Am. J. Gastroenterol. 111, 1104–1113 (2016).

    Article  PubMed  Google Scholar 

  113. Lahner, E. et al. Gender–sex differences in autoimmune atrophic gastritis. Transl. Res. 248, 1–10 (2022).

    Article  CAS  PubMed  Google Scholar 

  114. Landgren, A. M. et al. Autoimmune disease and subsequent risk of developing alimentary tract cancers among 4.5 million US male veterans. Cancer 117, 1163–1171 (2011).

    Article  PubMed  Google Scholar 

  115. Song, M. et al. Autoimmune diseases and gastric cancer risk: a systematic review and meta-analysis. Cancer Res. Treat. 51, 841–850 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  116. Wolfsen, H. C., Carpenter, H. A. & Talley, N. J. Menetrier’s disease: a form of hypertrophic gastropathy or gastritis? Gastroenterology 104, 1310–1319 (1993).

    Article  CAS  PubMed  Google Scholar 

  117. Megged, O. & Schlesinger, Y. Cytomegalovirus-associated protein-losing gastropathy in childhood. Eur. J. Pediatr. 167, 1217–1220 (2008).

    Article  CAS  PubMed  Google Scholar 

  118. Badov, D. et al. Helicobacter pylori as a pathogenic factor in Ménétrier’s disease. Am. J. Gastroenterol. 93, 1976–1979 (1998).

    Article  CAS  PubMed  Google Scholar 

  119. Madsen, L. G. et al. Ménétrier’s disease and Helicobacter pylori: normalization of gastrointestinal protein loss after eradication therapy. Dig. Dis. Sci. 44, 2307–2312 (1999).

    Article  CAS  PubMed  Google Scholar 

  120. Remes-Troche, J. M. et al. Early gastric cancer in Menetrier’s disease. BMJ Case Rep. 2009, bcr07.2008.0453 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  121. Kim, J. et al. Menetrier’s disease in Korea: report of two cases and review of cases in a gastric cancer prevalent region. Yonsei Med. J. 45, 555–560 (2004).

    Article  PubMed  Google Scholar 

  122. Kim, H. J. et al. Comparison between resectable Helicobacter pylori-negative and -positive gastric cancers. Gut Liver 10, 212–219 (2016).

    Article  CAS  PubMed  Google Scholar 

  123. Nguyen, T. H. et al. Prevalence of Helicobacter pylori positive non-cardia gastric adenocarcinoma is low and decreasing in a US population. Dig. Dis. Sci. 65, 2403–2411 (2020).

    Article  CAS  PubMed  Google Scholar 

  124. Matsuo, T. et al. Low prevalence of Helicobacter pylori-negative gastric cancer among Japanese. Helicobacter 16, 415–419 (2011).

    Article  PubMed  Google Scholar 

  125. Kageyama, S. et al. Characteristics of the salivary microbiota in patients with various digestive tract cancers. Front. Microbiol. 10, 1780 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  126. Sjöstedt, S. et al. Microbial colonization of tumors in relation to the upper gastrointestinal tract in patients with gastric carcinoma. Ann. Surg. 207, 341–346 (1988).

    Article  PubMed  PubMed Central  Google Scholar 

  127. Engstrand, L. & Graham, D. Y. Microbiome and gastric cancer. Dig. Dis. Sci. 65, 865–873 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Yamamoto, Y. et al. Helicobacter pylori-negative gastric cancer: characteristics and endoscopic findings. Dig. Endosc. 27, 551–561 (2015).

    Article  PubMed  Google Scholar 

  129. Cancer Genome Atlas Research Network. Comprehensive molecular characterization of gastric adenocarcinoma. Nature 513, 202–209 (2014).

    Article  Google Scholar 

  130. Soerjomataram, I. et al. Global burden of cancer in 2008: a systematic analysis of disability-adjusted life-years in 12 world regions. Lancet 380, 1840–1850 (2012).

    Article  PubMed  Google Scholar 

  131. Cai, Q. et al. Development and validation of a prediction rule for estimating gastric cancer risk in the Chinese high-risk population: a nationwide multicentre study. Gut 68, 1576–1587 (2019).

    Article  CAS  PubMed  Google Scholar 

  132. Thrift, A. P., Kanwal, F. & El-Serag, H. B. Prediction models for gastrointestinal and liver diseases: too many developed, too few validated. Clin. Gastroenterol. Hepatol. 14, 1678–1680 (2016).

    Article  PubMed  Google Scholar 

  133. Rokkas, T. & Graham, D. Y. How widespread and convenient H. pylori susceptibility testing will result in pharmacological opportunities. Expert Rev. Gastroenterol. Hepatol. 17, 1–7 (2023).

    Article  CAS  PubMed  Google Scholar 

  134. Ford, A. C., Yuan, Y. & Moayyedi, P. Helicobacter pylori eradication therapy to prevent gastric cancer: systematic review and meta-analysis. Gut 69, 2113–2121 (2020).

    Article  PubMed  Google Scholar 

  135. Chiang, T. H. et al. Mass eradication of Helicobacter pylori to reduce gastric cancer incidence and mortality: a long-term cohort study on Matsu Islands. Gut 70, 243–250 (2021).

    CAS  PubMed  Google Scholar 

  136. Piazuelo, M. B. et al. The Colombian Chemoprevention Trial: 20-year follow-up of a cohort of patients with gastric precancerous lesions. Gastroenterology 160, 1106–1117.e3 (2021).

    Article  PubMed  Google Scholar 

  137. Kumar, S. et al. Risk factors and incidence of gastric cancer after detection of Helicobacter pylori infection: a large cohort study. Gastroenterology 158, 527–536.e7 (2020).

    Article  CAS  PubMed  Google Scholar 

  138. Doorakkers, E. et al. Eradication of Helicobacter pylori and gastric cancer: a systematic review and meta-analysis of cohort studies. J. Natl. Cancer Inst. 108, djw132 (2016).

    Article  PubMed  Google Scholar 

  139. Pan, K. F. et al. A large randomised controlled intervention trial to prevent gastric cancer by eradication of Helicobacter pylori in Linqu County, China: baseline results and factors affecting the eradication. Gut 65, 9–18 (2016).

    Article  CAS  PubMed  Google Scholar 

  140. Khan, M. Y. et al. Effectiveness of Helicobacter pylori eradication in preventing metachronous gastric cancer and preneoplastic lesions. A systematic review and meta-analysis. Eur. J. Gastroenterol. Hepatol. 32, 686–694 (2020).

    PubMed  Google Scholar 

  141. Zeng, M. et al. Efficacy, safety, and immunogenicity of an oral recombinant Helicobacter pylori vaccine in children in China: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 386, 1457–1464 (2015).

    Article  CAS  PubMed  Google Scholar 

  142. IARC Helicobacter pylori Working Group. Helicobacter pylori Eradication as a Strategy for Preventing Gastric Cancer (IARC Working Group Reports, No. 8) (IARC, 2014).

  143. Areia, M. et al. Screening for gastric cancer and surveillance of premalignant lesions: a systematic review of cost-effectiveness studies. Helicobacter 18, 325–337 (2013).

    Article  PubMed  Google Scholar 

  144. El-Serag, H. B. et al. Houston consensus conference on testing for Helicobacter pylori infection in the United States. Clin. Gastroenterol. Hepatol. 16, 992–1002 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  145. Sugano, K. Screening of gastric cancer in Asia. Best. Pract. Res. Clin. Gastroenterol. 29, 895–905 (2015).

    Article  PubMed  Google Scholar 

  146. Choi, K. S. et al. Performance of different gastric cancer screening methods in Korea: a population-based study. PLoS ONE 7, e50041 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Yeh, J. M. et al. Gastric adenocarcinoma screening and prevention in the era of new biomarker and endoscopic technologies: a cost-effectiveness analysis. Gut 65, 563–574 (2016).

    Article  CAS  PubMed  Google Scholar 

  148. Gupta, N. et al. Endoscopy for upper GI cancer screening in the general population: a cost-utility analysis. Gastrointest. Endosc. 74, 610–624.e2 (2011).

    Article  PubMed  Google Scholar 

  149. Saumoy, M. et al. Cost effectiveness of gastric cancer screening according to race and ethnicity. Gastroenterology 155, 648–660 (2018).

    Article  PubMed  Google Scholar 

  150. Tashiro, A. et al. Comparing mass screening techniques for gastric cancer in Japan. World J. Gastroenterol. 12, 4873–4874 (2006).

    PubMed  PubMed Central  Google Scholar 

  151. Choi, K. S. & Suh, M. Screening for gastric cancer: the usefulness of endoscopy. Clin. Endosc. 47, 490–496 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  152. Asaka, M. A new approach for elimination of gastric cancer deaths in Japan. Int. J. Cancer 132, 1272–1276 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Asaka, M., Kato, M. & Sakamoto, N. Roadmap to eliminate gastric cancer with Helicobacter pylori eradication and consecutive surveillance in Japan. J. Gastroenterol. 49, 1–8 (2014).

    Article  CAS  PubMed  Google Scholar 

  154. World Health Organization. International Classification of Diseases for Oncology (ICD-O), 3rd edn, 1st revision (WHO, 2013).

Download references

Author information

Authors and Affiliations

  1. Section of Epidemiology and Population Sciences, Department of Medicine, Baylor College of Medicine, Houston, TX, USA

    Aaron P. Thrift

  2. Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA

    Aaron P. Thrift

  3. Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA

    Theresa Nguyen Wenker & Hashem B. El-Serag

  4. Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA

    Theresa Nguyen Wenker & Hashem B. El-Serag

Authors
  1. Aaron P. Thrift
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Theresa Nguyen Wenker
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hashem B. El-Serag
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

The authors contributed equally to all aspects of article preparation.

Corresponding author

Correspondence to Hashem B. El-Serag.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer reviewer information

Nature Reviews Clinical Oncology thanks J. Bornschein, M. Leja, P. Malfertheine and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Related links

SEER: www.seer.cancer.gov

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Thrift, A.P., Wenker, T.N. & El-Serag, H.B. Global burden of gastric cancer: epidemiological trends, risk factors, screening and prevention. Nat Rev Clin Oncol 20, 338–349 (2023). https://doi.org/10.1038/s41571-023-00747-0

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41571-023-00747-0

Search

Advanced search

Quick links

Nature Briefing: Cancer

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly. Sign up for Nature Briefing: Cancer