Article | Published:

Helicobacter pylori Infection Is Associated With Reduced Risk of Barrett’s Esophagus: An Analysis of the Barrett’s and Esophageal Adenocarcinoma Consortium

The American Journal of Gastroenterologyvolume 113pages11481155 (2018) | Download Citation




Epidemiological studies of Helicobacter pylori infection and risk of Barrett’s esophagus (BE) have reported conflicting results. We examined the association between H. pylori infection and BE and sought to determine whether the association is mediated by gastroesophageal reflux disease (GERD) and to identify potential effect modifiers.


We used individual level data from 1308 patients with BE (cases), 1388 population-based controls, and 1775 GERD controls in the Barrett’s and Esophageal Adenocarcinoma Consortium (BEACON). We estimated study-specific odds ratios (ORs) and 95% CIs using multivariable logistic regression models and obtained summary risk estimates using a random-effects meta-analytic approach. We examined potential effect modification by waist-to-hip ratio (WHR), body mass index (BMI), and smoking status by conducting stratified analyses.


For comparisons with population-based controls, H. pylori infection was inversely associated with the risk of BE (adjusted OR = 0.44, 95% CI = 0.36-0.55), with no evidence of between-study heterogeneity (I2 = 0%). A stronger inverse association between H. pylori and BE was observed among individuals with the CagA-positive strain (P for interaction = 0.017). We found no evidence of interaction between WHR, BMI, smoking status, and H. pylori infection on the risk of BE. There was no association between H. pylori infection and BE for comparisons with GERD controls (OR = 0.96, 95% CI = 0.67-1.37; I2 = 48%).


This study provides the strongest evidence yet that H. pylori infection is strongly inversely associated with BE. This effect is probably mediated by a decrease in GERD in infected patients, since the protective effect disappears in patients with GERD symptoms.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1.

    Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin. 2017;67:7–30.

  2. 2.

    Abnet CC, Arnold M, Wei W-Q. Epidemiology of esophageal squamous cell carcinoma. Gastroenterology. 2017.

  3. 3.

    Thrift AP, Whiteman DC. The incidence of esophageal adenocarcinoma continues to rise: analysis of period and birth cohort effects on recent trends. Ann Oncol. 2012;23:3155–62.

  4. 4.

    Vaughan TL, Fitzgerald RC. Precision prevention of oesophageal adenocarcinoma. Nat Rev Gastroenterol Hepatol. 2015;12:243–8.

  5. 5.

    Spechler SJ. Barrett’s esophagus and esophageal adenocarcinoma: pathogenesis, diagnosis, and therapy. Med Clin North Am. 2002;86:1423–45.

  6. 6.

    Cameron AJ, Ott BJ, Payne WS. The incidence of adenocarcinoma in columnar-lined (Barrett’s) esophagus. N Engl J Med. 1985;313:857–9.

  7. 7.

    Zagari RM, Fuccio L, Wallander M-A, et al. Gastro-oesophageal reflux symptoms, oesophagitis and Barrett’s oesophagus in the general population: the Loiano-Monghidoro study. Gut. 2008;57:1354–9.

  8. 8.

    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.

  9. 9.

    Rubenstein JH, Inadomi JM, Scheiman J, et al. Association between Helicobacter pylori and Barrett’s esophagus, erosive esophagitis, and gastroesophageal reflux symptoms. Clin Gastroenterol Hepatol. 2014;12:239–45.

  10. 10.

    Thrift AP, Kramer JR, Qureshi Z, Richardson PA, El-Serag HB. Age at onset of GERD symptoms predicts risk of Barrett’s esophagus. Am J Gastroenterol. 2013;108:915–22.

  11. 11.

    Thrift AP, Shaheen NJ, Gammon MD, et al. Obesity and risk of esophageal adenocarcinoma and Barrett’s esophagus: a Mendelian randomization study. J Natl Cancer Inst. 2014;106:dju252.

  12. 12.

    Cook MB, Shaheen NJ, Anderson LA, et al. Cigarette smoking increases risk of Barrett’s esophagus: an analysis of the Barrett’s and Esophageal Adenocarcinoma Consortium. Gastroenterology. 2012;142:744–53.

  13. 13.

    Plummer M, Franceschi S, Vignat J, Forman D, de Martel C. Global burden of gastric cancer attributable to Helicobacter pylori. Int J Cancer. 2015;136:487–90.

  14. 14.

    Runge TM, Abrams JA, Shaheen NJ. Epidemiology of Barrett’s esophagus and esophageal adenocarcinoma. Gastroenterol Clin North Am. 2015;44:203–31.

  15. 15.

    Grande M, Lisi G, De Sanctis F, et al. Does a relationship still exist between gastroesophageal reflux and Helicobacter pylori in patients with reflux symptoms? World J Surg Oncol. 2014;12:375.

  16. 16.

    Fischbach LA, Nordenstedt H, Kramer JR, et al. The association between Barrett’s esophagus and Helicobacter pylori infection: a meta-analysis. Helicobacter. 2012;17:163–75.

  17. 17.

    Fischbach LA, Graham DY, Kramer JR, et al. Association between Helicobacter pylori and Barrett’s esophagus: a case-control study. Am J Gastroenterol. 2014;109:357–68.

  18. 18.

    Anderson LA, Murphy SJ, Johnston BT, et al. Relationship between Helicobacter pylori infection and gastric atrophy and the stages of the oesophageal inflammation, metaplasia, adenocarcinoma sequence: results from the FINBAR case-control study. Gut. 2008;57:734–9.

  19. 19.

    Corley DA, Kubo A, Levin TR, et al. Helicobacter pylori infection and the risk of Barrett’s oesophagus: a community-based study. Gut. 2008;57:727–33.

  20. 20.

    Thrift AP, Pandeya N, Smith KJ, et al. Helicobacter pylori infection and the risks of Barrett’s oesophagus: a population-based case-control study. Int J Cancer. 2012;130:2407–16.

  21. 21.

    Parsonnet J, Replogle M, Yang S, Hiatt R. Seroprevalence of CagA-positive strains among Helicobacter pylori-infected, healthy young adults. J Infect Dis. 1997;175:1240–2.

  22. 22.

    Kendall BJ, Rubenstein JH, Cook MB, et al. Inverse association between gluteofemoral obesity and risk of Barrett’s esophagus in a pooled analysis. Clin Gastroenterol Hepatol Clin Pract J Am Gastroenterol Assoc. 2016;14:1412–9.

  23. 23.

    Kubo A, Cook MB, Shaheen NJ, et al. Sex-specific associations between body mass index, waist circumference and the risk of Barrett’s oesophagus: a pooled analysis from the international BEACON consortium. Gut. 2013;62:1684–91.

  24. 24.

    Thrift AP, Cook MB, Vaughan TL, et al. Alcohol and the risk of Barrett’s esophagus: a pooled analysis from the International BEACON Consortium. Am J Gastroenterol. 2014;109:1586–94.

  25. 25.

    Thrift AP, Anderson LA, Murray LJ, et al. Nonsteroidal anti-inflammatory drug use is not associated with reduced risk of Barrett’s esophagus. Am J Gastroenterol. 2016;111:1528–35.

  26. 26.

    Smith-Warner SA, Spiegelman D, Ritz J, et al. Methods for pooling results of epidemiologic studies: the Pooling Project of Prospective Studies of Diet and Cancer. Am J Epidemiol. 2006;163:1053–64.

  27. 27.

    Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60.

  28. 28.

    Rex DK, Cummings OW, Shaw M, et al. Screening for Barrett’s esophagus in colonoscopy patients with and without heartburn. Gastroenterology. 2003;125:1670–7.

  29. 29.

    Lam KD, Phan JT, Garcia RT, et al. Low proportion of Barrett’s esophagus in Asian Americans. Am J Gastroenterol. 2008;103:1625–30.

  30. 30.

    Werdmuller BF, Loffeld RJ. Helicobacter pylori infection has no role in the pathogenesis of reflux esophagitis. Dig Dis Sci. 1997;42:103–5.

  31. 31.

    Monkemuller K, Neumann H, Nocon M, et al. Serum gastrin and pepsinogens do not correlate with the different grades of severity of gastro-oesophageal reflux disease: a matched case-control study. Aliment Pharmacol Ther. 2008;28:491–6.

  32. 32.

    Peng S, Xiong L-S, Xiao Y-L, et al. Prompt upper endoscopy is an appropriate initial management in uninvestigated Chinese patients with typical reflux symptoms. Am J Gastroenterol. 2010;105:1947–52.

  33. 33.

    Rajendra S, Kutty K, Karim N. Ethnic differences in the prevalence of endoscopic esophagitis and Barrett’s esophagus: the long and short of it all. Dig Dis Sci. 2004;49:237–42.

Download references

Author information


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

    • Zhensheng Wang MPH, PhD
    •  & Aaron P. Thrift PhD
  2. Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, Chapel Hill, NC, USA

    • Nicholas J. Shaheen MD, MPH
  3. QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia

    • David C. Whiteman MBBS, PhD
  4. Centre for Public Health, Queen’s University Belfast, Belfast, Northern Ireland

    • Lesley A. Anderson PhD, MPH
  5. Program in Epidemiology, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    • Thomas L. Vaughan MD, MPH
  6. Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA

    • Douglas A. Corley MD, PhD
  7. San Francisco Medical Center, Kaiser Permanente Northern California, San Francisco, CA, USA

    • Douglas A. Corley MD, PhD
  8. Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA

    • Hashem B. El-Serag MD, MPH
  9. Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E DeBakey Veterans Affairs Medical Center, Houston, TX, USA

    • Hashem B. El-Serag MD, MPH
  10. Center for Clinical Management Research, Ann Arbor Veterans Affairs Medical Center, Ann Arbor, MI, USA

    • Joel H. Rubenstein MD, MSc
  11. Barrett’s Esophagus Program, Division of Gastroenterology Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA

    • Joel H. Rubenstein MD, MSc
  12. Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA

    • Aaron P. Thrift PhD


  1. Search for Zhensheng Wang MPH, PhD in:

  2. Search for Nicholas J. Shaheen MD, MPH in:

  3. Search for David C. Whiteman MBBS, PhD in:

  4. Search for Lesley A. Anderson PhD, MPH in:

  5. Search for Thomas L. Vaughan MD, MPH in:

  6. Search for Douglas A. Corley MD, PhD in:

  7. Search for Hashem B. El-Serag MD, MPH in:

  8. Search for Joel H. Rubenstein MD, MSc in:

  9. Search for Aaron P. Thrift PhD in:

Guarantor of the article

Aaron P. Thrift, PhD.

Specific author contributions

ZW and APT contributed to data analysis, interpretation of data, and drafting of the manuscript. NJS, DCW, LAA, TLV, DAC, HBE-S, and JHR designed the study; obtained funding; collected data from individual case–control studies; and contributed to the concept of the consortium, interpretation of data, and refinement of the manuscript. All authors approved the final draft submitted.

Financial support

This work was supported by the National Institutes of Health RO1 DK63616 (to DAC), 1R21DK077742 (to NJS and DAC), K23DK59311 (to NJS), R03 DK75842 (to NJS), K23DK079291 (to JHR), R01 CA116845 (to HBE-S), K24-04-107 (to HBE-S); an Ireland–Northern Ireland cooperation research project grant sponsored by the Northern Ireland Research and Development Office and the Health Research Board, Ireland (FINBAR) (RES/1699/01N/S); the Study of Digestive Health, NCI RO1 CA 001833 (to DCW); the Established Investigator Award in Cancer Prevention and Control, K05 CA124911 (to TLV), and the US Department of Veterans Affairs CSRD Merit I01-CX000899 (to JHR). ZW is supported by a Research Training Grant from the Cancer Prevention and Research Institute of Texas (CPRIT; RP160097).

Potential competing interests


Corresponding author

Correspondence to Aaron P. Thrift PhD.

Electronic supplementary material

About this article

Publication history





Further reading