Skip to main content

Advertisement

SpringerLink
Log in

Risk Factors for Rising Incidence of Esophageal and Gastric Cardia Adenocarcinoma

  • Review Article
  • Published:
Journal of Gastrointestinal Cancer Aims and scope Submit manuscript

Abstract

Introduction

In the last 30 years, the incidence of esophageal and gastric cardia adenocarcinoma has steadily increased. The increase in incidence is approximately seven-fold, which is a more substantial increase than that of several malignancies, including melanoma, breast cancer, and prostate cancer.

Discussion

The rising incidence has led to a steady increase in mortality from 2 to 15 deaths per 100,000 in the last three decades. The etiologic factors involved in the development of these malignancies include gastroesophageal reflux disease, Barrett’s esophagus, acid-suppressive medication use, obesity, and tobacco use. This article discusses the contribution of these etiologic risk factors to this increase in incidence.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. El-Serag HB. Time trends of gastroesophageal reflux disease: a systematic review. Clin Gastroenterol Hepatol. 2007;5:17–26.

    Article  PubMed  Google Scholar 

  2. Pohl H, Sirovich B, Welch HG. Esophageal adenocarcinoma incidence: are we reaching the peak? Cancer Epidemiol Biomarkers Prev. 2010;19:1468–70.

    Article  PubMed  Google Scholar 

  3. Desai HG, Kamani PM. Factors responsible for the increasing incidence of oesophageal adenocarcinoma. J Assoc Physicians India. 2007;55:435–7.

    PubMed  CAS  Google Scholar 

  4. Simard EP, Ward EM, Siegel R, Jemal A. Cancers with increasing incidence trends in the United States: 1999 through 2008. CA Cancer J Clin 2012.

  5. Moayyedi P, Talley NJ. Gastro-oesophageal reflux disease. Lancet. 2006;367:2086–100.

    Article  PubMed  Google Scholar 

  6. Kim R, Weissfeld JL, Reynolds JC, Kuller LH. Etiology of Barrett’s metaplasia and esophageal adenocarcinoma. Cancer Epidemiol Biomarkers Prev. 1997;6:369–77.

    PubMed  CAS  Google Scholar 

  7. Wu AH, Wan P, Bernstein L. A multiethnic population-based study of smoking, alcohol and body size and risk of adenocarcinomas of the stomach and esophagus (United States). Cancer Causes Control. 2001;12:721–32.

    Article  PubMed  CAS  Google Scholar 

  8. Wu AH, Tseng CC, Bernstein L. Hiatal hernia, reflux symptoms, body size, and risk of esophageal and gastric adenocarcinoma. Cancer. 2003;98:940–8.

    Article  PubMed  Google Scholar 

  9. Garcia Rodriguez LA, Lagergren J, Lindblad M. Gastric acid suppression and risk of oesophageal and gastric adenocarcinoma: a nested case control study in the UK. Gut. 2006;55:1538–44.

    Article  PubMed  CAS  Google Scholar 

  10. Farrow DC, Vaughan TL, Sweeney C, et al. Gastroesophageal reflux disease, use of H2 receptor antagonists, and risk of esophageal and gastric cancer. Cancer Causes Control. 2000;11:231–8.

    Article  PubMed  CAS  Google Scholar 

  11. Lagergren J, Bergstrom R, Lindgren A, Nyren O. Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N Engl J Med. 1999;340:825–31.

    Article  PubMed  CAS  Google Scholar 

  12. Chow WH, Finkle WD, McLaughlin JK, et al. The relation of gastroesophageal reflux disease and its treatment to adenocarcinomas of the esophagus and gastric cardia. JAMA. 1995;274:474–7.

    Article  PubMed  CAS  Google Scholar 

  13. Solaymani-Dodaran M, Logan RF, West J, et al. Risk of oesophageal cancer in Barrett’s oesophagus and gastro-oesophageal reflux. Gut. 2004;53:1070–4.

    Article  PubMed  CAS  Google Scholar 

  14. Chak A, Faulx A, Eng C, et al. Gastroesophageal reflux symptoms in patients with adenocarcinoma of the esophagus or cardia. Cancer. 2006;107:2160–6.

    Article  PubMed  Google Scholar 

  15. Sharma P, McQuaid K, Dent J, et al. A critical review of the diagnosis and management of Barrett’s esophagus: the AGA Chicago Workshop. Gastroenterology. 2004;127:310–30.

    Article  PubMed  Google Scholar 

  16. Ronkainen J, Aro P, Storskrubb T, et al. Prevalence of Barrett’s esophagus in the general population: an endoscopic study. Gastroenterology. 2005;129:1825–31.

    Article  PubMed  Google Scholar 

  17. Shaheen NJ, Crosby MA, Bozymski EM, Sandler RS. Is there publication bias in the reporting of cancer risk in Barrett’s esophagus? Gastroenterology. 2000;119:333–8.

    Article  PubMed  CAS  Google Scholar 

  18. Thomas T, Abrams KR, De Caestecker JS, Robinson RJ. Meta analysis: cancer risk in Barrett’s oesophagus. Aliment Pharmacol Ther. 2007;26:1465–77.

    Article  PubMed  CAS  Google Scholar 

  19. Hvid-Jensen F, Pedersen L, Drewes AM, et al. Incidence of adenocarcinoma among patients with Barrett’s esophagus. N Engl J Med. 2011;365:1375–83.

    Article  PubMed  CAS  Google Scholar 

  20. Moayyedi P, Burch N, Akhtar-Danesh N, et al. Mortality rates in patients with Barrett’s oesophagus. Aliment Pharmacol Ther. 2008;27:316–20.

    Article  PubMed  CAS  Google Scholar 

  21. van der Burgh A, Dees J, Hop WC, van Blankenstein M. Oesophageal cancer is an uncommon cause of death in patients with Barrett’s oesophagus. Gut. 1996;39:5–8.

    Article  PubMed  Google Scholar 

  22. Weston AP, Krmpotich PT, Cherian R, et al. Prospective long-term endoscopic and histological follow-up of short segment Barrett’s esophagus: comparison with traditional long segment Barrett’s esophagus. Am J Gastroenterol. 1997;92:407–13.

    PubMed  CAS  Google Scholar 

  23. Weston AP, Sharma P, Mathur S, et al. Risk stratification of Barrett’s esophagus: updated prospective multivariate analysis. Am J Gastroenterol. 2004;99:1657–66.

    Article  PubMed  Google Scholar 

  24. Avidan B, Sonnenberg A, Schnell TG, et al. Hiatal hernia size, Barrett’s length, and severity of acid reflux are all risk factors for esophageal adenocarcinoma. Am J Gastroenterol. 2002;97:1930–6.

    Article  PubMed  Google Scholar 

  25. Rudolph RE, Vaughan TL, Storer BE, et al. Effect of segment length on risk for neoplastic progression in patients with Barrett esophagus. Ann Intern Med. 2000;132:612–20.

    Article  PubMed  CAS  Google Scholar 

  26. Sharma P, Falk GW, Weston AP, et al. Dysplasia and cancer in a large multicenter cohort of patients with Barrett’s esophagus. Clin Gastroenterol Hepatol. 2006;4:566–72.

    Article  PubMed  Google Scholar 

  27. Hameeteman W, Tytgat GN, Houthoff HJ, van den Tweel JG. Barrett’s esophagus: development of dysplasia and adenocarcinoma. Gastroenterology. 1989;96:1249–56.

    PubMed  CAS  Google Scholar 

  28. van Sandick JW, van Lanschot JJ, Kuiken BW, et al. Impact of endoscopic biopsy surveillance of Barrett’s oesophagus on pathological stage and clinical outcome of Barrett’s carcinoma. Gut. 1998;43:216–22.

    Article  PubMed  Google Scholar 

  29. Montgomery E, Bronner MP, Goldblum JR, et al. Reproducibility of the diagnosis of dysplasia in Barrett esophagus: a reaffirmation. Hum Pathol. 2001;32:368–78.

    Article  PubMed  CAS  Google Scholar 

  30. Skacel M, Petras RE, Gramlich TL, et al. The diagnosis of low-grade dysplasia in Barrett’s esophagus and its implications for disease progression. Am J Gastroenterol. 2000;95:3383–7.

    Article  PubMed  CAS  Google Scholar 

  31. Weston AP, Banerjee SK, Sharma P, et al. p53 protein overexpression in low grade dysplasia (LGD) in Barrett’s esophagus: immunohistochemical marker predictive of progression. Am J Gastroenterol. 2001;96:1355–62.

    Article  PubMed  CAS  Google Scholar 

  32. Dulai GS, Shekelle PG, Jensen DM, et al. Dysplasia and risk of further neoplastic progression in a regional Veterans Administration Barrett’s cohort. Am J Gastroenterol. 2005;100:775–83.

    Article  PubMed  Google Scholar 

  33. Srivastava A, Hornick JL, Li X, et al. Extent of low-grade dysplasia is a risk factor for the development of esophageal adenocarcinoma in Barrett’s esophagus. Am J Gastroenterol. 2007;102:483–93. quiz 694.

    Article  PubMed  Google Scholar 

  34. Sharma P. Low-grade dysplasia in Barrett’s esophagus. Gastroenterology. 2004;127:1233–8.

    Article  PubMed  Google Scholar 

  35. Pellegrini CA, Pohl D. High-grade dysplasia in Barrett’s esophagus: surveillance or operation? J Gastrointest Surg. 2000;4:131–4.

    Article  PubMed  CAS  Google Scholar 

  36. Buttar NS, Wang KK, Sebo TJ, et al. Extent of high-grade dysplasia in Barrett’s esophagus correlates with risk of adenocarcinoma. Gastroenterology. 2001;120:1630–9.

    Article  PubMed  CAS  Google Scholar 

  37. Rastogi A, Puli S, El-Serag HB, et al. Incidence of esophageal adenocarcinoma in patients with Barrett’s esophagus and high-grade dysplasia: a meta-analysis. Gastrointest Endosc. 2008;67:394–8.

    Article  PubMed  Google Scholar 

  38. Reid BJ, Prevo LJ, Galipeau PC, et al. Predictors of progression in Barrett’s esophagus II: baseline 17p (p53) loss of heterozygosity identifies a patient subset at increased risk for neoplastic progression. Am J Gastroenterol. 2001;96:2839–48.

    Article  PubMed  CAS  Google Scholar 

  39. Bian YS, Osterheld MC, Fontolliet C, et al. p16 inactivation by methylation of the CDKN2A promoter occurs early during neoplastic progression in Barrett’s esophagus. Gastroenterology. 2002;122:1113–21.

    Article  PubMed  CAS  Google Scholar 

  40. Reid BJ, Haggitt RC, Rubin CE, Rabinovitch PS. Barrett’s esophagus. Correlation between flow cytometry and histology in detection of patients at risk for adenocarcinoma. Gastroenterology. 1987;93:1–11.

    PubMed  CAS  Google Scholar 

  41. Reid BJ. p53 and neoplastic progression in Barrett’s esophagus. Am J Gastroenterol. 2001;96:1321–3.

    Article  PubMed  CAS  Google Scholar 

  42. Wong DJ, Paulson TG, Prevo LJ, et al. p16(INK4a) lesions are common, early abnormalities that undergo clonal expansion in Barrett’s metaplastic epithelium. Cancer Res. 2001;61:8284–9.

    PubMed  CAS  Google Scholar 

  43. Schulmann K, Sterian A, Berki A, et al. Inactivation of p16, RUNX3, and HPP1 occurs early in Barrett’s-associated neoplastic progression and predicts progression risk. Oncogene. 2005;24:4138–48.

    Article  PubMed  CAS  Google Scholar 

  44. Galipeau PC, Li X, Blount PL, et al. NSAIDs modulate CDKN2A, TP53, and DNA content risk for progression to esophageal adenocarcinoma. PLoS Med. 2007;4:e67.

    Article  PubMed  Google Scholar 

  45. Vaughan TL, Davis S, Kristal A, Thomas DB. Obesity, alcohol, and tobacco as risk factors for cancers of the esophagus and gastric cardia: adenocarcinoma versus squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev. 1995;4:85–92.

    PubMed  CAS  Google Scholar 

  46. Merry AH, Schouten LJ, Goldbohm RA, van den Brandt PA. Body mass index, height and risk of adenocarcinoma of the oesophagus and gastric cardia: a prospective cohort study. Gut. 2007;56:1503–11.

    Article  PubMed  Google Scholar 

  47. Lagergren J, Bergstrom R, Nyren O. Association between body mass and adenocarcinoma of the esophagus and gastric cardia. Ann Intern Med. 1999;130:883–90.

    Article  PubMed  CAS  Google Scholar 

  48. Whiteman DC, Sadeghi S, Pandeya N, et al. Combined effects of obesity, acid reflux and smoking on the risk of adenocarcinomas of the oesophagus. Gut. 2008;57:173–80.

    Article  PubMed  CAS  Google Scholar 

  49. Corley DA, Kubo A, Zhao W. Abdominal obesity and the risk of esophageal and gastric cardia carcinomas. Cancer Epidemiol Biomarkers Prev. 2008;17:352–8.

    Article  PubMed  Google Scholar 

  50. Hampel H, Abraham NS, El-Serag HB. Meta-analysis: obesity and the risk for gastroesophageal reflux disease and its complications. Ann Intern Med. 2005;143:199–211.

    Article  PubMed  Google Scholar 

  51. Kubo A, Corley DA. Body mass index and adenocarcinomas of the esophagus or gastric cardia: a systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev. 2006;15:872–8.

    Article  PubMed  Google Scholar 

  52. Ryan AM, Healy LA, Power DG, et al. Barrett esophagus: prevalence of central adiposity, metabolic syndrome, and a proinflammatory state. Ann Surg. 2008;247:909–15.

    Article  PubMed  Google Scholar 

  53. Moayyedi P. Barrett’s esophagus and obesity: the missing part of the puzzle. Am J Gastroenterol. 2008;103:301–3.

    Article  PubMed  Google Scholar 

  54. Engel LS, Chow WH, Vaughan TL, et al. Population attributable risks of esophageal and gastric cancers. J Natl Cancer Inst. 2003;95:1404–13.

    Article  PubMed  Google Scholar 

  55. Navarro Silvera SA, Mayne ST, Risch H, et al. Food group intake and risk of subtypes of esophageal and gastric cancer. Int J Cancer. 2008;123:852–60.

    Article  PubMed  Google Scholar 

  56. Chen H, Tucker KL, Graubard BI, et al. Nutrient intakes and adenocarcinoma of the esophagus and distal stomach. Nutr Cancer. 2002;42:33–40.

    Article  PubMed  Google Scholar 

  57. Thompson CL, Khiani V, Chak A, et al. Carbohydrate consumption and esophageal cancer:an ecological assessment. Am J Gastroenterol. 2008;103:555–61.

    Article  PubMed  CAS  Google Scholar 

  58. Falk GW. Risk factors for esophageal cancer development. Surg Oncol Clin N Am. 2009;18:469–85.

    Article  PubMed  Google Scholar 

  59. de Jonge PJ, Steyerberg EW, Kuipers EJ, et al. Risk factors for the development of esophageal adenocarcinoma in Barrett’s esophagus. Am J Gastroenterol. 2006;101:1421–9.

    Article  PubMed  Google Scholar 

  60. Lindblad M, Rodriguez LA, Lagergren J. Body mass, tobacco and alcohol and risk of esophageal, gastric cardia, and gastric non-cardia adenocarcinoma among men and women in a nested case-control study. Cancer Causes Control. 2005;16:285–94.

    Article  PubMed  Google Scholar 

  61. Gammon MD, Schoenberg JB, Ahsan H, et al. Tobacco, alcohol, and socioeconomic status and adenocarcinomas of the esophagus and gastric cardia. J Natl Cancer Inst. 1997;89:1277–84.

    Article  PubMed  CAS  Google Scholar 

  62. Brown LM, Silverman DT, Pottern LM, et al. Adenocarcinoma of the esophagus and esophagogastric junction in white men in the United States: alcohol, tobacco, and socioeconomic factors. Cancer Causes Control. 1994;5:333–40.

    Article  PubMed  CAS  Google Scholar 

  63. Lagergren J, Bergstrom R, Lindgren A, Nyren O. The role of tobacco, snuff and alcohol use in the aetiology of cancer of the oesophagus and gastric cardia. Int J Cancer. 2000;85:340–6.

    Article  PubMed  CAS  Google Scholar 

  64. Zhao DL, Chen WQ, Yu TT, et al. [A population-based matched case-control study on the risk factors of gastric cardia cancer]. Zhonghua Zhong Liu Za Zhi. 2011;33:775–8.

    PubMed  Google Scholar 

  65. Cook MB, Kamangar F, Whiteman DC, et al. Cigarette smoking and adenocarcinomas of the esophagus and esophagogastric junction: a pooled analysis from the international BEACON consortium. J Natl Cancer Inst. 2010;102:1344–53.

    Article  PubMed  CAS  Google Scholar 

  66. Pandeya N, Webb PM, Sadeghi S, et al. Gastro-oesophageal reflux symptoms and the risks of oesophageal cancer: are the effects modified by smoking, NSAIDs or acid suppressants? Gut. 2010;59:31–8.

    Article  PubMed  CAS  Google Scholar 

  67. El-Serag HB, Aguirre TV, Davis S, et al. Proton pump inhibitors are associated with reduced incidence of dysplasia in Barrett’s esophagus. Am J Gastroenterol. 2004;99:1877–83.

    Article  PubMed  CAS  Google Scholar 

  68. Hillman LC, Chiragakis L, Shadbolt B, et al. Proton-pump inhibitor therapy and the development of dysplasia in patients with Barrett’s oesophagus. Med J Aust. 2004;180:387–91.

    PubMed  Google Scholar 

  69. De Jonge PJ, Siersema PD, Van Breda SG, et al. Proton pump inhibitor therapy in gastro-oesophageal reflux disease decreases the oesophageal immune response but does not reduce the formation of DNA adducts. Aliment Pharmacol Ther. 2008;28:127–36.

    Article  PubMed  Google Scholar 

  70. Hillman LC, Chiragakis L, Shadbolt B, et al. Effect of proton pump inhibitors on markers of risk for high-grade dysplasia and oesophageal cancer in Barrett’s oesophagus. Aliment Pharmacol Ther. 2008;27:321–6.

    Article  PubMed  CAS  Google Scholar 

  71. Tamim H, Duranceau A, Chen LQ, Lelorier J. Association between use of acid-suppressive drugs and risk of gastric cancer. A nested case-control study. Drug Saf. 2008;31:675–84.

    Article  PubMed  Google Scholar 

  72. DeMeester SR, DeMeester TR. Columnar mucosa and intestinal metaplasia of the esophagus: fifty years of controversy. Ann Surg. 2000;231:303–21.

    Article  PubMed  CAS  Google Scholar 

  73. Ye W, Chow WH, Lagergren J, et al. Risk of adenocarcinomas of the esophagus and gastric cardia in patients with gastroesophageal reflux diseases and after antireflux surgery. Gastroenterology. 2001;121:1286–93.

    Article  PubMed  CAS  Google Scholar 

  74. Tran T, Spechler SJ, Richardson P, El-Serag HB. Fundoplication and the risk of esophageal cancer in gastroesophageal reflux disease: a Veterans Affairs cohort study. Am J Gastroenterol. 2005;100:1002–8.

    Article  PubMed  Google Scholar 

  75. Kubo A, Corley DA. Marked multi-ethnic variation of esophageal and gastric cardia carcinomas within the United States. Am J Gastroenterol. 2004;99:582–8.

    Article  PubMed  Google Scholar 

  76. Ji J, Hemminki K. Familial risk for esophageal cancer: an updated epidemiologic study from Sweden. Clin Gastroenterol Hepatol. 2006;4:840–5.

    Article  PubMed  Google Scholar 

  77. Chak A, Lee T, Kinnard MF, et al. Familial aggregation of Barrett’s oesophagus, oesophageal adenocarcinoma, and oesophagogastric junctional adenocarcinoma in Caucasian adults. Gut. 2002;51:323–8.

    Article  PubMed  CAS  Google Scholar 

  78. Dhillon PK, Farrow DC, Vaughan TL, et al. Family history of cancer and risk of esophageal and gastric cancers in the United States. Int J Cancer. 2001;93:148–52.

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of Interest

The authors have declared no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Surgery, University of North Carolina, Chapel Hill, NC, USA

    Jacquelyn S. Carr

  2. Department of Hematology and Medical Oncology, Emory University, 1365 Clifton Road NE, Atlanta, GA, 300322, USA

    Syed F. Zafar, Nabil Saba, Fadlo R. Khuri & Bassel F. El-Rayes

Authors
  1. Jacquelyn S. Carr
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Syed F. Zafar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nabil Saba
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fadlo R. Khuri
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Bassel F. El-Rayes
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bassel F. El-Rayes.

Additional information

Jacquelyn S. Carr and Syed F. Zafar contributed equally to this review.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Carr, J.S., Zafar, S.F., Saba, N. et al. Risk Factors for Rising Incidence of Esophageal and Gastric Cardia Adenocarcinoma. J Gastrointest Canc 44, 143–151 (2013). https://doi.org/10.1007/s12029-013-9480-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12029-013-9480-z

Keywords

Search

Navigation