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Influence of obesity on the risk of esophageal disorders

Nature Reviews Gastroenterology & Hepatology volume 8, pages 340–347 (2011)Cite this article

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Abstract

Obesity is associated with an increased risk of esophageal disorders, including esophageal adenocarcinoma, Barrett esophagus and GERD. For reasons yet unknown, the association between obesity and esophageal adenocarcinoma seems to be stronger than that for other types of obesity-related cancers. Predominantly abdominal or intra-abdominal adiposity (representing visceral fat and other fat within the abdominal cavity), which is more frequently observed in men than in women, is more strongly linked with these esophageal disorders than BMI alone, a finding that might contribute to the striking male predominance of esophageal adenocarcinoma. Research has identified potential mechanisms underlying the strong link between obesity and esophageal conditions. These findings are summarized in this Review, but more research remains to be carried out before these mechanisms are established.

Key Points

  • Obesity, particularly with a predominantly abdominal distribution of fat, is associated with an increased risk of esophageal adenocarcinoma, Barrett esophagus and GERD

  • Increase in BMI correlates clearly and proportionally with an increased risk of esophageal adenocarcinoma and GERD; however, corresponding data regarding Barrett esophagus are less clear

  • Body fat distribution, especially the presence of abdominal adiposity, is a factor in the link between obesity and esophageal disorders

  • Molecular mechanisms involving leptin, adiponectin and estrogen have been proposed to explain the association between obesity and these esophageal conditions

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References

  1. Vial, M., Grande, L. & Pera, M. Epidemiology of adenocarcinoma of the esophagus, gastric cardia, and upper gastric third. Recent Results Cancer Res. 182, 1–17 (2010).

    PubMed  Google Scholar 

  2. Lagergren, J. & Lagergren, P. Oesophageal cancer. BMJ 341, c6280 (2010).

    Article  Google Scholar 

  3. Sharma, P. Clinical practice. Barrett's esophagus. N. Engl. J. Med. 361, 2548–2556 (2009).

    Article  CAS  Google Scholar 

  4. Badreddine, R. J. & Wang, K. K. Barrett esophagus: an update. Nat. Rev. Gastroenterol. Hepatol. 7, 369–378 (2010).

    Article  Google Scholar 

  5. Kahrilas, P. J. Clinical practice. Gastroesophageal reflux disease. N. Engl. J. Med. 359, 1700–1707 (2008).

    Article  CAS  Google Scholar 

  6. WHO. Obesity: Preventing and Managing the Global Epidemic. Report of a WHO Consultation (Stationery Office Books, London, 2000).

  7. Jaffrin, M. Y. Body composition determination by bioimpedance: an update. Curr. Opin. Clin. Nutr. Metab. Care 12, 482–486 (2009).

    Article  Google Scholar 

  8. Andreoli, A., Scalzo, G., Masala, S., Tarantino, U. & Guglielmi, G. Body composition assessment by dual-energy X-ray absorptiometry (DXA). Radiol. Med. 114, 286–300 (2009).

    Article  CAS  Google Scholar 

  9. Brown, L. M. et al. Adenocarcinoma of the esophagus: role of obesity and diet. J. Natl Cancer Inst. 87, 104–109 (1995).

    Article  CAS  Google Scholar 

  10. Vaughan, T. L., Davis, S., Kristal, A. & Thomas, D. B. Obesity, alcohol, and tobacco as risk factors for cancers of the esophagus and gastric cardia: adenocarcinoma versus squamous cell carcinoma. Cancer Epidemiol. Biomarkers Prev. 4, 85–92 (1995).

    CAS  PubMed  Google Scholar 

  11. Chow, W. H. et al. Body mass index and risk of adenocarcinomas of the esophagus and gastric cardia. J. Natl Cancer Inst. 90, 150–155 (1998).

    Article  CAS  Google Scholar 

  12. Whiteman, D. C. et al. Combined effects of obesity, acid reflux and smoking on the risk of adenocarcinomas of the oesophagus. Gut 57, 173–180 (2008).

    Article  CAS  Google Scholar 

  13. Lindblad, M., Rodríguez, L. A. & 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 16, 285–294 (2005).

    Article  Google Scholar 

  14. Engeland, A., Tretli, S. & Bjørge, T. Height and body mass index in relation to esophageal cancer; 23-year follow-up of two million Norwegian men and women. Cancer Causes Control 15, 837–843 (2004).

    Article  Google Scholar 

  15. Merry, A. H., Schouten, L. J., Goldbohm, R. A. & van den Brandt, P. A. Body mass index, height and risk of adenocarcinoma of the oesophagus and gastric cardia: a prospective cohort study. Gut 56, 1503–1511 (2007).

    Article  Google Scholar 

  16. Abnet, C. C. et al. A prospective study of BMI and risk of oesophageal and gastric adenocarcinoma. Eur. J. Cancer 44, 465–471 (2008).

    Article  Google Scholar 

  17. Löfdahl, H. E., Lu, Y. & Lagergren, J. Sex-specific risk factor profile in oesophageal adenocarcinoma. Br. J. Cancer 99, 1506–1510 (2008).

    Article  Google Scholar 

  18. Chak, A. et al. Assessment of familiality, obesity, and other risk factors for early age of cancer diagnosis in adenocarcinomas of the esophagus and gastroesophageal junction. Am. J. Gastroenterol. 104, 1913–1921 (2009).

    Article  Google Scholar 

  19. Calle, E. E., Rodriguez, C., Walker-Thurmond, K. & Thun, M. J. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of, U. S. adults. N. Engl. J. Med. 348, 1625–1638 (2003).

    Article  Google Scholar 

  20. Renehan, A. G., Tyson, M., Egger, M., Heller, R. F. & Zwahlen, M. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 371, 569–578 (2008).

    Article  Google Scholar 

  21. Lagergren, J., Bergström, R. & Nyrén, O. Association between body mass and adenocarcinoma of the esophagus and gastric cardia. Ann. Intern. Med. 130, 883–890 (1999).

    Article  CAS  Google Scholar 

  22. Samanic, C., Chow, W. H., Gridley, G., Jarvholm, B. & Fraumeni, J. F. Jr Relation of body mass index to cancer risk in 362,552 Swedish men. Cancer Causes Control 17, 901–909 (2006).

    Article  Google Scholar 

  23. Nordenstedt, H. & El-Serag, H. The influence of age, sex, and race on the incidence of esophageal cancer in the United States (1992–2006). Scand. J. Gastroenterol. doi:10.3109/00365521.2011.551890.

  24. Lagergren, J. & Mattsson, F. No further increase in the incidence of esophageal adenocarcinoma in Sweden. Int. J. Cancer doi:10.1002/ijc.2 5701.

  25. Lagergren, J., Bergström, R., Lindgren, A. & Nyrén, O. Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N. Engl. J. Med. 340, 825–831 (1999).

    Article  CAS  Google Scholar 

  26. MacInnis, R. J., English, D. R., Hopper, J. L. & Giles, G. G. Body size and composition and the risk of gastric and oesophageal adenocarcinoma. Int. J. Cancer 118, 2628–2631 (2006).

    Article  CAS  Google Scholar 

  27. Steffen, A. et al. Anthropometry and esophageal cancer risk in the European prospective investigation into cancer and nutrition. Cancer Epidemiol. Biomarkers Prev. 18, 2079–2089 (2009).

    Article  Google Scholar 

  28. Corley, D. A., Kubo, A. & Zhao, W. Abdominal obesity and the risk of esophageal and gastric cardia carcinomas. Cancer Epidemiol. Biomarkers Prev. 17, 352–358 (2008).

    Article  Google Scholar 

  29. Beddy, P. et al. Association of visceral adiposity with oesophageal and junctional adenocarcinomas. Br. J. Surg. 97, 1028–1034 (2010).

    Article  CAS  Google Scholar 

  30. Lagergren, J., Ye, W., Bergström, R. & Nyrén, O. Utility of endoscopic screening for upper gastrointestinal adenocarcinoma. JAMA 284, 961–962 (2000).

    Article  CAS  Google Scholar 

  31. Ortiz, V. et al. Value of heartburn for diagnosing gastroesophageal reflux disease in severely obese patients. Obesity (Silver Spring) 14, 696–700 (2006).

    Article  Google Scholar 

  32. Küper, M. A. et al. Dysfunction of the lower esophageal sphincter and dysmotility of the tubular esophagus in morbidly obese patients. Obes. Surg. 19, 1143–1149 (2009).

    Article  Google Scholar 

  33. McElholm, A. R. et al. A population-based study of IGF axis polymorphisms and the esophageal inflammation, metaplasia, adenocarcinoma sequence. Gastroenterology 139, 204–212 (2010).

    Article  CAS  Google Scholar 

  34. MacDonald, K., Porter, G. A., Guernsey, D. L., Zhao, R. & Casson, A. G. A polymorphic variant of the insulin-like growth factor type I receptor gene modifies risk of obesity for esophageal adenocarcinoma. Cancer Epidemiol. 33, 37–40 (2009).

    Article  CAS  Google Scholar 

  35. Ogunwobi, O. O. & Beales, I. L. Leptin stimulates the proliferation of human oesophageal adenocarcinoma cells via HB-EGF and Tgfα mediated transactivation of the epidermal growth factor receptor. Br. J. Biomed. Sci. 65, 121–127 (2008).

    Article  CAS  Google Scholar 

  36. Brochu-Gaudreau, K. et al. Adiponectin action from head to toe. Endocrine 37, 11–32 (2010).

    Article  CAS  Google Scholar 

  37. Howard, J. M. et al. Associations between leptin and adiponectin receptor upregulation, visceral obesity and tumour stage in oesophageal and junctional adenocarcinoma. Br. J. Surg. 97, 1020–1027 (2010).

    Article  CAS  Google Scholar 

  38. Doecke, J. D. et al. Single nucleotide polymorphisms in obesity-related genes and the risk of esophageal cancers. Cancer Epidemiol. Biomarkers Prev. 17, 1007–1012 (2008).

    Article  CAS  Google Scholar 

  39. Stein, D. J., El-Serag, H. B., Kuczynski, J., Kramer, J. R. & Sampliner, R. E. The association of body mass index with Barrett's oesophagus. Aliment. Pharmacol. Ther. 22, 1005–1010 (2005).

    Article  CAS  Google Scholar 

  40. Smith, K. J. et al. Interactions among smoking, obesity, and symptoms of acid reflux in Barrett's esophagus. Cancer Epidemiol. Biomarkers Prev. 14, 2481–2486 (2005).

    Article  Google Scholar 

  41. Healy, L. A., Ryan, A. M., Pidgeon, G., Ravi, N. & Reynolds, J. V. Lack of differential pattern in central adiposity and metabolic syndrome in Barrett's esophagus and gastroesophageal reflux disease. Dis. Esophagus 23, 386–391 (2010).

    CAS  PubMed  Google Scholar 

  42. Gerson, L. B. et al. Does body mass index differ between patients with Barrett's oesophagus and patients with chronic gastro-oesophageal reflux disease? Aliment. Pharmacol. Ther. 25, 1079–1086 (2007).

    Article  CAS  Google Scholar 

  43. Corley, D. A. et al. Abdominal obesity and body mass index as risk factors for Barrett's esophagus. Gastroenterology 133, 34–41 (2007).

    Article  Google Scholar 

  44. Smith, K. J. et al. Current and past smoking significantly increase risk for Barrett's esophagus. Clin. Gastroenterol. Hepatol. 7, 840–848 (2009).

    Article  Google Scholar 

  45. Edelstein, Z. R., Farrow, D. C., Bronner, M. P., Rosen, S. N. & Vaughan, T. L. Central adiposity and risk of Barrett's esophagus. Gastroenterology 133, 403–411 (2007).

    Article  Google Scholar 

  46. Caygill, C. P. et al. Lifestyle factors and Barrett's esophagus. Am. J. Gastroenterol. 97, 1328–1331 (2002).

    Article  Google Scholar 

  47. El-Serag, H. B., Kvapil, P., Hacken-Bitar, J. & Kramer, J. R. Abdominal obesity and the risk of Barrett's esophagus. Am. J. Gastroenterol. 100, 2151–2156 (2005).

    Article  Google Scholar 

  48. Akiyama, T. et al. Visceral obesity and the risk of Barrett's esophagus in Japanese patients with non-alcoholic fatty liver disease. BMC Gastroenterol. 9, 56 (2009).

    Article  Google Scholar 

  49. Rubenstein, J. H. et al. A pilot study of the association of low plasma adiponectin and Barrett's esophagus. Am. J. Gastroenterol. 103, 1358–1364 (2008).

    Article  CAS  Google Scholar 

  50. Sowers, J. R. Endocrine functions of adipose tissue: focus on adiponectin. Clin. Cornerstone 9, 32–38 (2008).

    Article  Google Scholar 

  51. Rubenstein, J. H. et al. Association of adiponectin multimers with Barrett's oesophagus. Gut 58, 1583–1589 (2009).

    Article  CAS  Google Scholar 

  52. Ryan, A. M. et al. Barrett esophagus: prevalence of central adiposity, metabolic syndrome, and a proinflammatory state. Ann. Surg. 247, 909–915 (2008).

    Article  Google Scholar 

  53. Kendall, B. J. et al. Leptin and the risk of Barrett's oesophagus. Gut 57, 448–454 (2008).

    CAS  Google Scholar 

  54. Lagergren, J., Bergström, R. & Nyrén, O. No relation between body mass and gastro-oesophageal reflux symptoms in a Swedish population based study. Gut 47, 26–29 (2000).

    Article  CAS  Google Scholar 

  55. Nilsson, M., Johnsen, R., Ye, W., Hveem, K. & Lagergren, J. Obesity and estrogen as risk factors for gastroesophageal reflux symptoms. JAMA 290, 66–72 (2003).

    Article  CAS  Google Scholar 

  56. Jacobson, B. C., Somers, S. C., Fuchs, C. S., Kelly, C. P. & Camargo, C. A. Jr. Body-mass index and symptoms of gastroesophageal reflux in women. N. Engl. J. Med. 354, 2340–2348 (2006).

    Article  CAS  Google Scholar 

  57. Murray, L. et al. Relationship between body mass and gastro-oesophageal reflux symptoms: the Bristol Helicobacter Project. Int. J. Epidemiol. 32, 645–650 (2003).

    Article  Google Scholar 

  58. Nandurkar, S. et al. Relationship between body mass index, diet, exercise and gastro-oesophageal reflux symptoms in a community. Aliment. Pharmacol. Ther. 20, 497–505 (2004).

    Article  CAS  Google Scholar 

  59. Hampel, H., Abraham, N. S. & El-Serag, H. B. Meta-analysis: obesity and the risk for gastroesophageal reflux disease and its complications. Ann. Intern. Med. 143, 199–211 (2005).

    Article  Google Scholar 

  60. Corley, D. A. & Kubo, A. Body mass index and gastroesophageal reflux disease: a systematic review and meta-analysis. Am. J. Gastroenterol. 101, 2619–2628 (2006).

    Article  Google Scholar 

  61. Solhpour, A. et al. Gastro-esophageal reflux symptoms and body mass index: no relation among the Iranian population. Indian J. Gastroenterol. 27, 153–155 (2008).

    PubMed  Google Scholar 

  62. Corley, D. A., Kubo, A. & Zhao, W. Abdominal obesity, ethnicity and gastro-oesophageal reflux symptoms. Gut 56, 756–762 (2007).

    Article  Google Scholar 

  63. Gunji, T. et al. Risk factors for erosive esophagitis: a cross-sectional study of a large number of Japanese males. J. Gastroenterol. doi:10.1007/s00535-010-0359-0355.

  64. Zheng, Z. et al. Effects of estrogen with and without progestin and obesity on symptomatic gastroesophageal reflux. Gastroenterology 135, 72–81 (2008).

    Article  Google Scholar 

  65. Chung, S. J. et al. Metabolic syndrome and visceral obesity as risk factors for reflux oesophagitis: a cross-sectional case-control study of 7078 Koreans undergoing health check-ups. Gut 57, 1360–1365 (2008).

    Article  CAS  Google Scholar 

  66. Nam, S. Y. et al. Abdominal visceral adipose tissue volume is associated with increased risk of erosive esophagitis in men and women. Gastroenterology 139, 1902–1911 (2010).

    Article  Google Scholar 

  67. de Vries, D. R., van Herwaarden, M. A., Smout, A. J. & Samsom, M. Gastroesophageal pressure gradients in gastroesophageal reflux disease: relations with hiatal hernia, body mass index, and esophageal acid exposure. Am. J. Gastroenterol. 103, 1349–1354 (2008).

    Article  Google Scholar 

  68. Crowell, M. D. et al. Obesity is associated with increased 48-h esophageal acid exposure in patients with symptomatic gastroesophageal reflux. Am. J. Gastroenterol. 104, 553–559 (2009).

    Article  Google Scholar 

  69. Ayazi, S. et al. Obesity and gastroesophageal reflux: quantifying the association between body mass index, esophageal acid exposure, and lower esophageal sphincter status in a large series of patients with reflux symptoms. J. Gastrointest. Surg. 13, 1440–1447 (2009).

    Article  Google Scholar 

  70. Menon, S. & Trudgill, N. Risk factors in the aetiology of hiatus hernia: a meta-analysis. Eur. J. Gastroenterol. Hepatol. 23, 133–138 (2011).

    Article  Google Scholar 

  71. Nilsson, M., Lundegårdh, G., Carling, L., Ye, W. & Lagergren, J. Body mass and reflux oesophagitis: an oestrogen-dependent association? Scand. J. Gastroenterol. 37, 626–630 (2002).

    Article  CAS  Google Scholar 

  72. Nordenstedt, H. et al. Postmenopausal hormone therapy as a risk factor for gastroesophageal reflux symptoms among female twins. Gastroenterology 134, 921–928 (2008).

    Article  Google Scholar 

  73. De Groot, N. L. et al. Systematic review: the effects of conservative and surgical treatment for obesity on gastro-oesophageal reflux disease. Aliment. Pharmacol. Ther. 30, 1091–1102 (2009).

    Article  CAS  Google Scholar 

  74. Flegal, K. M., Carroll, M. D., Ogden, C. L. & Curtin, L. R. Prevalence and trends in obesity among US adults, 1999–2008. JAMA 303, 235–241 (2010).

    Article  CAS  Google Scholar 

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Acknowledgements

The author is supported by grants from the Swedish Cancer Society and the Swedish Research Council. These funding agencies were not involved in the design or implementation of the study, the collection, management, analysis, or interpretation of the data, or the preparation, review, or approval of the manuscript. C. P. Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape, LLC-accredited continuing medical education activity associated with this article.

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  1. Department of Molecular Medicine and Surgery, Karolinska Institutet, Upper Gastrointestinal Research, Norra Stationsgatan 67, 2nd floor, SE-171 76, Stockholm, Sweden

    Jesper Lagergren

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Lagergren, J. Influence of obesity on the risk of esophageal disorders. Nat Rev Gastroenterol Hepatol 8, 340–347 (2011). https://doi.org/10.1038/nrgastro.2011.73

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