Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate®

Epidemiology, pathobiology, and clinical manifestations of esophageal cancer

Michael K Gibson, MD, PhD, FACP
Section Editors
Kenneth K Tanabe, MD
Richard M Goldberg, MD
Deputy Editor
Diane MF Savarese, MD


The majority of esophageal cancers are squamous cell or adenocarcinomas. Although the incidence of squamous cell carcinoma (SCC) is decreasing in the United States, the incidence of adenocarcinoma arising out of Barrett's esophagus is rising dramatically, although less so in the last few years [1]. When stratified according to anatomic location, most of the increased incidence involves tumors at the esophagogastric junction (EGJ) and gastric cardia (figure 1) [2].

The epidemiology, etiologic factors, and clinical manifestations of adenocarcinoma and SCC of the esophagus will be reviewed here. Small cell carcinoma and sarcomas arising in the esophagus and EGJ as well as the diagnosis, staging, and treatment of esophageal cancer are discussed separately. (See "Extrapulmonary small cell cancer" and "Local treatment for gastrointestinal stromal tumors, leiomyomas, and leiomyosarcomas of the gastrointestinal tract", section on 'Esophagus' and "Diagnosis and staging of esophageal cancer".)


In the United States, an estimated 16,910 cases of esophageal cancer will be diagnosed each year and 15,690 deaths are expected from the disease [3]. Worldwide, an estimated 455,800 new esophageal cancer cases and 400,200 deaths occurred in 2012 [4].

Incidence rates vary internationally by nearly 16-fold, with the highest rates found in Southern and Eastern Africa and Eastern Asia, and the lowest rates in Western and Middle Africa and Central America in both males and females [5]. In the highest-risk area, stretching from Northern Iran through the central Asian republics to North-Central China (often referred to as the "esophageal cancer belt"), 90 percent of cases are squamous cell carcinomas (SCC) [6,7]. Major risk factors in these areas are not well understood, but are thought to include poor nutritional status, low intake of fruits and vegetables, and drinking beverages at high temperatures. In contrast, in low-risk areas such as the United States and several Western countries, smoking and excessive alcohol consumption account for about 90 percent of the total cases of esophageal SCC [8]. Country-specific rates of incidence and mortality are available in the World Health Organization GLOBOCAN database. (See 'Smoking and alcohol' below.)

Temporal trends in incidence vary for the two major histologic types of esophageal cancer. Incidence rates for adenocarcinoma of the esophagus have been increasing dramatically in several Western countries, in part due to increases in known risk factors such as overweight and obesity [1]. When stratified according to anatomic location, most of the increased incidence involves tumors at the esophagogastric junction (EGJ) and gastric cardia (figure 1) [2].


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Dec 2016. | This topic last updated: Fri Sep 09 00:00:00 GMT+00:00 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Pohl H, Sirovich B, Welch HG. Esophageal adenocarcinoma incidence: are we reaching the peak? Cancer Epidemiol Biomarkers Prev 2010; 19:1468.
  2. Buas MF, Vaughan TL. Epidemiology and risk factors for gastroesophageal junction tumors: understanding the rising incidence of this disease. Semin Radiat Oncol 2013; 23:3.
  3. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin 2016; 66:7.
  4. Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012. CA Cancer J Clin 2015; 65:87.
  5. Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin 2011; 61:69.
  6. Gholipour C, Shalchi RA, Abbasi M. A histopathological study of esophageal cancer on the western side of the Caspian littoral from 1994 to 2003. Dis Esophagus 2008; 21:322.
  7. Tran GD, Sun XD, Abnet CC, et al. Prospective study of risk factors for esophageal and gastric cancers in the Linxian general population trial cohort in China. Int J Cancer 2005; 113:456.
  8. Engel LS, Chow WH, Vaughan TL, et al. Population attributable risks of esophageal and gastric cancers. J Natl Cancer Inst 2003; 95:1404.
  9. Lu CL, Lang HC, Luo JC, et al. Increasing trend of the incidence of esophageal squamous cell carcinoma, but not adenocarcinoma, in Taiwan. Cancer Causes Control 2010; 21:269.
  10. Chang-Claude J, Becher H, Blettner M, et al. Familial aggregation of oesophageal cancer in a high incidence area in China. Int J Epidemiol 1997; 26:1159.
  11. Li JY, Ershow AG, Chen ZJ, et al. A case-control study of cancer of the esophagus and gastric cardia in Linxian. Int J Cancer 1989; 43:755.
  12. 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.
  13. Sun X, Chandar AK, Elston R, Chak A. What we know and what we need to know about familial gastroesophageal reflux disease and Barrett's esophagus. Clin Gastroenterol Hepatol 2014; 12:1664.
  14. Hemminki K, Jiang Y. Familial and second esophageal cancers: a nation-wide epidemiologic study from Sweden. Int J Cancer 2002; 98:106.
  15. Lagergren J, Ye W, Lindgren A, Nyrén O. Heredity and risk of cancer of the esophagus and gastric cardia. Cancer Epidemiol Biomarkers Prev 2000; 9:757.
  16. 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.
  17. Ji J, Hemminki K. Familial risk for esophageal cancer: an updated epidemiologic study from Sweden. Clin Gastroenterol Hepatol 2006; 4:840.
  18. Parkin DM, Läärä E, Muir CS. Estimates of the worldwide frequency of sixteen major cancers in 1980. Int J Cancer 1988; 41:184.
  19. Boersma E, Harrington RA, Moliterno DJ, et al. Platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes. Lancet 2002; 360:342.
  20. Marjani HA, Biramijamal F, Hossein-Nezhad A, et al. Prevalence of esophageal cancer risk factors among Turkmen and non-Turkmen ethnic groups in a high incidence area in Iran. Arch Iran Med 2010; 13:111.
  21. Yang CS. Research on esophageal cancer in China: a review. Cancer Res 1980; 40:2633.
  22. He Z, Zhao Y, Guo C, et al. Prevalence and risk factors for esophageal squamous cell cancer and precursor lesions in Anyang, China: a population-based endoscopic survey. Br J Cancer 2010; 103:1085.
  23. Pottern LM, Morris LE, Blot WJ, et al. Esophageal cancer among black men in Washington, D.C. I. Alcohol, tobacco, and other risk factors. J Natl Cancer Inst 1981; 67:777.
  24. 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.
  25. Thun MJ, Peto R, Lopez AD, et al. Alcohol consumption and mortality among middle-aged and elderly U.S. adults. N Engl J Med 1997; 337:1705.
  26. Pandeya N, Williams G, Green AC, et al. Alcohol consumption and the risks of adenocarcinoma and squamous cell carcinoma of the esophagus. Gastroenterology 2009; 136:1215.
  27. Islami F, Fedirko V, Tramacere I, et al. Alcohol drinking and esophageal squamous cell carcinoma with focus on light-drinkers and never-smokers: a systematic review and meta-analysis. Int J Cancer 2011; 129:2473.
  28. Freedman ND, Abnet CC, Caporaso NE, et al. Impact of changing US cigarette smoking patterns on incident cancer: risks of 20 smoking-related cancers among the women and men of the NIH-AARP cohort. Int J Epidemiol 2016; 45:846.
  29. Chen ZM, Xu Z, Collins R, et al. Early health effects of the emerging tobacco epidemic in China. A 16-year prospective study. JAMA 1997; 278:1500.
  30. Iribarren C, Tekawa IS, Sidney S, Friedman GD. Effect of cigar smoking on the risk of cardiovascular disease, chronic obstructive pulmonary disease, and cancer in men. N Engl J Med 1999; 340:1773.
  31. Randi G, Scotti L, Bosetti C, et al. Pipe smoking and cancers of the upper digestive tract. Int J Cancer 2007; 121:2049.
  32. Tuyns AJ, Péquignot G, Abbatucci JS. Oesophageal cancer and alcohol consumption; importance of type of beverage. Int J Cancer 1979; 23:443.
  33. Brown LM, Hoover R, Gridley G, et al. Drinking practices and risk of squamous-cell esophageal cancer among Black and White men in the United States. Cancer Causes Control 1997; 8:605.
  34. Hori H, Kawano T, Endo M, Yuasa Y. Genetic polymorphisms of tobacco- and alcohol-related metabolizing enzymes and human esophageal squamous cell carcinoma susceptibility. J Clin Gastroenterol 1997; 25:568.
  35. Hashibe M, McKay JD, Curado MP, et al. Multiple ADH genes are associated with upper aerodigestive cancers. Nat Genet 2008; 40:707.
  36. Druesne-Pecollo N, Tehard B, Mallet Y, et al. Alcohol and genetic polymorphisms: effect on risk of alcohol-related cancer. Lancet Oncol 2009; 10:173.
  37. Lu SH, Montesano R, Zhang MS, et al. Relevance of N-nitrosamines to esophageal cancer in China. J Cell Physiol Suppl 1986; 4:51.
  38. Islami F, Ren JS, Taylor PR, Kamangar F. Pickled vegetables and the risk of oesophageal cancer: a meta-analysis. Br J Cancer 2009; 101:1641.
  39. Wang L, Zhu D, Zhang C, et al. Mutations of O6-methylguanine-DNA methyltransferase gene in esophageal cancer tissues from Northern China. Int J Cancer 1997; 71:719.
  40. Cheng SJ, Sala M, Li MH, Chouroulinkov I. Esophageal cancer in Linxian county, China: a possible etiology and mechanism (initiation and promotion). Carcinog Compr Surv 1982; 7:167.
  41. Siddiqi M, Tricker AR, Preussmann R. The occurrence of preformed N-nitroso compounds in food samples from a high risk area of esophageal cancer in Kashmir, India. Cancer Lett 1988; 39:37.
  42. Chu FS, Li GY. Simultaneous occurrence of fumonisin B1 and other mycotoxins in moldy corn collected from the People's Republic of China in regions with high incidences of esophageal cancer. Appl Environ Microbiol 1994; 60:847.
  43. Pickwell SM, Schimelpfening S, Palinkas LA. 'Betelmania'. Betel quid chewing by Cambodian women in the United States and its potential health effects. West J Med 1994; 160:326.
  44. Akhtar S, Sheikh AA, Qureshi HU. Chewing areca nut, betel quid, oral snuff, cigarette smoking and the risk of oesophageal squamous-cell carcinoma in South Asians: a multicentre case-control study. Eur J Cancer 2012; 48:655.
  45. Trivedy C, Baldwin D, Warnakulasuriya S, et al. Copper content in Areca catechu (betel nut) products and oral submucous fibrosis. Lancet 1997; 349:1447.
  46. Islami F, Boffetta P, Ren JS, et al. High-temperature beverages and foods and esophageal cancer risk--a systematic review. Int J Cancer 2009; 125:491.
  47. Islami F, Pourshams A, Nasrollahzadeh D, et al. Tea drinking habits and oesophageal cancer in a high risk area in northern Iran: population based case-control study. BMJ 2009; 338:b929.
  48. Wu M, Liu AM, Kampman E, et al. Green tea drinking, high tea temperature and esophageal cancer in high- and low-risk areas of Jiangsu Province, China: a population-based case-control study. Int J Cancer 2009; 124:1907.
  49. Cross AJ, Freedman ND, Ren J, et al. Meat consumption and risk of esophageal and gastric cancer in a large prospective study. Am J Gastroenterol 2011; 106:432.
  50. Keszei AP, Schouten LJ, Goldbohm RA, van den Brandt PA. Red and processed meat consumption and the risk of esophageal and gastric cancer subtypes in The Netherlands Cohort Study. Ann Oncol 2012; 23:2319.
  51. Mark SD, Qiao YL, Dawsey SM, et al. Prospective study of serum selenium levels and incident esophageal and gastric cancers. J Natl Cancer Inst 2000; 92:1753.
  52. Steevens J, van den Brandt PA, Goldbohm RA, Schouten LJ. Selenium status and the risk of esophageal and gastric cancer subtypes: the Netherlands cohort study. Gastroenterology 2010; 138:1704.
  53. Li B, Taylor PR, Li JY, et al. Linxian nutrition intervention trials. Design, methods, participant characteristics, and compliance. Ann Epidemiol 1993; 3:577.
  54. Blot WJ, Li JY, Taylor PR, et al. Nutrition intervention trials in Linxian, China: supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population. J Natl Cancer Inst 1993; 85:1483.
  55. Blot WJ, Li JY. Some considerations in the design of a nutrition intervention trial in Linxian, People's Republic of China. Natl Cancer Inst Monogr 1985; 69:29.
  56. Mark SD, Liu SF, Li JY, et al. The effect of vitamin and mineral supplementation on esophageal cytology: results from the Linxian Dysplasia Trial. Int J Cancer 1994; 57:162.
  57. Limburg PJ, Wei W, Ahnen DJ, et al. Randomized, placebo-controlled, esophageal squamous cell cancer chemoprevention trial of selenomethionine and celecoxib. Gastroenterology 2005; 129:863.
  58. Abnet CC, Lai B, Qiao YL, et al. Zinc concentration in esophageal biopsy specimens measured by x-ray fluorescence and esophageal cancer risk. J Natl Cancer Inst 2005; 97:301.
  59. Fong LY, Sivak A, Newberne PM. Zinc deficiency and methylbenzylnitrosamine-induced esophageal cancer in rats. J Natl Cancer Inst 1978; 61:145.
  60. Fong LY, Magee PN. Dietary zinc deficiency enhances esophageal cell proliferation and N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumor incidence in C57BL/6 mouse. Cancer Lett 1999; 143:63.
  61. Fong LY, Nguyen VT, Farber JL. Esophageal cancer prevention in zinc-deficient rats: rapid induction of apoptosis by replenishing zinc. J Natl Cancer Inst 2001; 93:1525.
  62. Fong LY, Zhang L, Jiang Y, Farber JL. Dietary zinc modulation of COX-2 expression and lingual and esophageal carcinogenesis in rats. J Natl Cancer Inst 2005; 97:40.
  63. Larsson SC, Giovannucci E, Wolk A. Folate intake, MTHFR polymorphisms, and risk of esophageal, gastric, and pancreatic cancer: a meta-analysis. Gastroenterology 2006; 131:1271.
  64. Xiao Q, Freedman ND, Ren J, et al. Intakes of folate, methionine, vitamin B6, and vitamin B12 with risk of esophageal and gastric cancer in a large cohort study. Br J Cancer 2014; 110:1328.
  65. Liu J, Wang J, Leng Y, Lv C. Intake of fruit and vegetables and risk of esophageal squamous cell carcinoma: a meta-analysis of observational studies. Int J Cancer 2013; 133:473.
  66. Sandler RS, Nyrén O, Ekbom A, et al. The risk of esophageal cancer in patients with achalasia. A population-based study. JAMA 1995; 274:1359.
  67. Appelqvist P, Salmo M. Lye corrosion carcinoma of the esophagus: a review of 63 cases. Cancer 1980; 45:2655.
  68. Tachibana M, Abe S, Yoshimura H, et al. Squamous cell carcinoma of the esophagus after partial gastrectomy. Dysphagia 1995; 10:49.
  69. Birgisson S, Rice TW, Easley KA, Richter JE. The lack of association between adenocarcinoma of the esophagus and gastric surgery: a retrospective study. Am J Gastroenterol 1997; 92:216.
  70. Islami F, Sheikhattari P, Ren JS, Kamangar F. Gastric atrophy and risk of oesophageal cancer and gastric cardia adenocarcinoma--a systematic review and meta-analysis. Ann Oncol 2011; 22:754.
  71. Chang F, Syrjänen S, Wang L, Syrjänen K. Infectious agents in the etiology of esophageal cancer. Gastroenterology 1992; 103:1336.
  72. Lam KY, He D, Ma L, et al. Presence of human papillomavirus in esophageal squamous cell carcinomas of Hong Kong Chinese and its relationship with p53 gene mutation. Hum Pathol 1997; 28:657.
  73. Chang F, Syrjänen S, Shen Q, et al. Human papillomavirus involvement in esophageal carcinogenesis in the high-incidence area of China. A study of 700 cases by screening and type-specific in situ hybridization. Scand J Gastroenterol 2000; 35:123.
  74. Far AE, Aghakhani A, Hamkar R, et al. Frequency of human papillomavirus infection in oesophageal squamous cell carcinoma in Iranian patients. Scand J Infect Dis 2007; 39:58.
  75. Shuyama K, Castillo A, Aguayo F, et al. Human papillomavirus in high- and low-risk areas of oesophageal squamous cell carcinoma in China. Br J Cancer 2007; 96:1554.
  76. Castillo A, Aguayo F, Koriyama C, et al. Human papillomavirus in esophageal squamous cell carcinoma in Colombia and Chile. World J Gastroenterol 2006; 12:6188.
  77. Syrjänen KJ. HPV infections and oesophageal cancer. J Clin Pathol 2002; 55:721.
  78. Campo MS. Papillomas and cancer in cattle. Cancer Surv 1987; 6:39.
  79. Sitas F, Egger S, Urban MI, et al. InterSCOPE study: Associations between esophageal squamous cell carcinoma and human papillomavirus serological markers. J Natl Cancer Inst 2012; 104:147.
  80. Dillner J, Knekt P, Schiller JT, Hakulinen T. Prospective seroepidemiological evidence that human papillomavirus type 16 infection is a risk factor for oesophageal squamous cell carcinoma. BMJ 1995; 311:1346.
  81. Bjørge T, Hakulinen T, Engeland A, et al. A prospective, seroepidemiological study of the role of human papillomavirus in esophageal cancer in Norway. Cancer Res 1997; 57:3989.
  82. Lagergren J, Wang Z, Bergström R, et al. Human papillomavirus infection and esophageal cancer: a nationwide seroepidemiologic case-control study in Sweden. J Natl Cancer Inst 1999; 91:156.
  83. Han C, Qiao G, Hubbert NL, et al. Serologic association between human papillomavirus type 16 infection and esophageal cancer in Shaanxi Province, China. J Natl Cancer Inst 1996; 88:1467.
  84. Sitas F, Urban M, Stein L, et al. The relationship between anti-HPV-16 IgG seropositivity and cancer of the cervix, anogenital organs, oral cavity and pharynx, oesophagus and prostate in a black South African population. Infect Agent Cancer 2007; 2:6.
  85. Li X, Gao C, Yang Y, et al. Systematic review with meta-analysis: the association between human papillomavirus infection and oesophageal cancer. Aliment Pharmacol Ther 2014; 39:270.
  86. Petrick JL, Wyss AB, Butler AM, et al. Prevalence of human papillomavirus among oesophageal squamous cell carcinoma cases: systematic review and meta-analysis. Br J Cancer 2014; 110:2369.
  87. IARC Monorgraphs Working Group. IARC Monographs on the Evaluation of Carcinogenic Risks to Hymans: International Agency for Research on Cancer. Volume 100 Part B: Biological Agents. Lyon, France: IARC; 2011.
  88. Stevens HP, Kelsell DP, Bryant SP, et al. Linkage of an American pedigree with palmoplantar keratoderma and malignancy (palmoplantar ectodermal dysplasia type III) to 17q24. Literature survey and proposed updated classification of the keratodermas. Arch Dermatol 1996; 132:640.
  89. Iwaya T, Maesawa C, Ogasawara S, Tamura G. Tylosis esophageal cancer locus on chromosome 17q25.1 is commonly deleted in sporadic human esophageal cancer. Gastroenterology 1998; 114:1206.
  90. 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; 63:570.
  91. Wysowski DK. Reports of esophageal cancer with oral bisphosphonate use. N Engl J Med 2009; 360:89.
  92. Ribeiro A, DeVault KR, Wolfe JT 3rd, Stark ME. Alendronate-associated esophagitis: endoscopic and pathologic features. Gastrointest Endosc 1998; 47:525.
  93. Abraham SC, Cruz-Correa M, Lee LA, et al. Alendronate-associated esophageal injury: pathologic and endoscopic features. Mod Pathol 1999; 12:1152.
  94. Cardwell CR, Abnet CC, Cantwell MM, Murray LJ. Exposure to oral bisphosphonates and risk of esophageal cancer. JAMA 2010; 304:657.
  95. Ribeiro U Jr, Posner MC, Safatle-Ribeiro AV, Reynolds JC. Risk factors for squamous cell carcinoma of the oesophagus. Br J Surg 1996; 83:1174.
  96. Cooper JS, Pajak TF, Rubin P, et al. Second malignancies in patients who have head and neck cancer: incidence, effect on survival and implications based on the RTOG experience. Int J Radiat Oncol Biol Phys 1989; 17:449.
  97. Erkal HS, Mendenhall WM, Amdur RJ, et al. Synchronous and metachronous squamous cell carcinomas of the head and neck mucosal sites. J Clin Oncol 2001; 19:1358.
  98. Shiozaki H, Tahara H, Kobayashi K, et al. Endoscopic screening of early esophageal cancer with the Lugol dye method in patients with head and neck cancers. Cancer 1990; 66:2068.
  99. Tincani AJ, Brandalise N, Altemani A, et al. Diagnosis of superficial esophageal cancer and dysplasia using endoscopic screening with a 2% lugol dye solution in patients with head and neck cancer. Head Neck 2000; 22:170.
  100. Petit T, Georges C, Jung GM, et al. Systematic esophageal endoscopy screening in patients previously treated for head and neck squamous-cell carcinoma. Ann Oncol 2001; 12:643.
  101. Muto M, Hironaka S, Nakane M, et al. Association of multiple Lugol-voiding lesions with synchronous and metachronous esophageal squamous cell carcinoma in patients with head and neck cancer. Gastrointest Endosc 2002; 56:517.
  102. Atabek U, Mohit-Tabatabai MA, Rush BF, et al. Impact of esophageal screening in patients with head and neck cancer. Am Surg 1990; 56:289.
  103. Ina H, Shibuya H, Ohashi I, Kitagawa M. The frequency of a concomitant early esophageal cancer in male patients with oral and oropharyngeal cancer. Screening results using Lugol dye endoscopy. Cancer 1994; 73:2038.
  104. Dar NA, Islami F, Bhat GA, et al. Poor oral hygiene and risk of esophageal squamous cell carcinoma in Kashmir. Br J Cancer 2013; 109:1367.
  105. Abnet CC, Qiao YL, Dawsey SM, et al. Tooth loss is associated with increased risk of total death and death from upper gastrointestinal cancer, heart disease, and stroke in a Chinese population-based cohort. Int J Epidemiol 2005; 34:467.
  106. Abnet CC, Kamangar F, Islami F, et al. Tooth loss and lack of regular oral hygiene are associated with higher risk of esophageal squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev 2008; 17:3062.
  107. Guha N, Boffetta P, Wünsch Filho V, et al. Oral health and risk of squamous cell carcinoma of the head and neck and esophagus: results of two multicentric case-control studies. Am J Epidemiol 2007; 166:1159.
  108. Hiraki A, Matsuo K, Suzuki T, et al. Teeth loss and risk of cancer at 14 common sites in Japanese. Cancer Epidemiol Biomarkers Prev 2008; 17:1222.
  109. Michaud DS, Liu Y, Meyer M, et al. Periodontal disease, tooth loss, and cancer risk in male health professionals: a prospective cohort study. Lancet Oncol 2008; 9:550.
  110. Abnet CC, Kamangar F, Dawsey SM, et al. Tooth loss is associated with increased risk of gastric non-cardia adenocarcinoma in a cohort of Finnish smokers. Scand J Gastroenterol 2005; 40:681.
  111. Bollschweiler E, Wolfgarten E, Gutschow C, Hölscher AH. Demographic variations in the rising incidence of esophageal adenocarcinoma in white males. Cancer 2001; 92:549.
  112. Blot WJ, Devesa SS, Kneller RW, Fraumeni JF Jr. Rising incidence of adenocarcinoma of the esophagus and gastric cardia. JAMA 1991; 265:1287.
  113. Blot WJ. Esophageal cancer trends and risk factors. Semin Oncol 1994; 21:403.
  114. Daly JM, Karnell LH, Menck HR. National Cancer Data Base report on esophageal carcinoma. Cancer 1996; 78:1820.
  115. Bytzer P, Christensen PB, Damkier P, et al. Adenocarcinoma of the esophagus and Barrett's esophagus: a population-based study. Am J Gastroenterol 1999; 94:86.
  116. Brown LM, Devesa SS. Epidemiologic trends in esophageal and gastric cancer in the United States. Surg Oncol Clin N Am 2002; 11:235.
  117. Edgren G, Adami HO, Weiderpass E, Nyrén O. A global assessment of the oesophageal adenocarcinoma epidemic. Gut 2013; 62:1406.
  118. Cook MB, Chow WH, Devesa SS. Oesophageal cancer incidence in the United States by race, sex, and histologic type, 1977-2005. Br J Cancer 2009; 101:855.
  119. Lagergren J, Mattsson F. No further increase in the incidence of esophageal adenocarcinoma in Sweden. Int J Cancer 2011; 129:513.
  120. Schmassmann A, Oldendorf MG, Gebbers JO. Changing incidence of gastric and oesophageal cancer subtypes in central Switzerland between 1982 and 2007. Eur J Epidemiol 2009; 24:603.
  121. Brown LM, Devesa SS, Chow WH. Incidence of adenocarcinoma of the esophagus among white Americans by sex, stage, and age. J Natl Cancer Inst 2008; 100:1184.
  122. El-Serag HB, Mason AC, Petersen N, Key CR. Epidemiological differences between adenocarcinoma of the oesophagus and adenocarcinoma of the gastric cardia in the USA. Gut 2002; 50:368.
  123. Hur C, Miller M, Kong CY, et al. Trends in esophageal adenocarcinoma incidence and mortality. Cancer 2013; 119:1149.
  124. Ekström AM, Signorello LB, Hansson LE, et al. Evaluating gastric cancer misclassification: a potential explanation for the rise in cardia cancer incidence. J Natl Cancer Inst 1999; 91:786.
  125. Pohl H, Welch HG. The role of overdiagnosis and reclassification in the marked increase of esophageal adenocarcinoma incidence. J Natl Cancer Inst 2005; 97:142.
  126. Zhai R, Chen F, Liu G, et al. Interactions among genetic variants in apoptosis pathway genes, reflux symptoms, body mass index, and smoking indicate two distinct etiologic patterns of esophageal adenocarcinoma. J Clin Oncol 2010; 28:2445.
  127. Drahos J, Xiao Q, Risch HA, et al. Age-specific risk factor profiles of adenocarcinomas of the esophagus: A pooled analysis from the international BEACON consortium. Int J Cancer 2016; 138:55.
  128. Lagergren J, Bergström R, Lindgren A, Nyrén O. Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N Engl J Med 1999; 340:825.
  129. Rubenstein JH, Taylor JB. Meta-analysis: the association of oesophageal adenocarcinoma with symptoms of gastro-oesophageal reflux. Aliment Pharmacol Ther 2010; 32:1222.
  130. 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.
  131. Lagergren J, Ye W, Lagergren P, Lu Y. The risk of esophageal adenocarcinoma after antireflux surgery. Gastroenterology 2010; 138:1297.
  132. 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.
  133. 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.
  134. Tramacere I, La Vecchia C, Negri E. Tobacco smoking and esophageal and gastric cardia adenocarcinoma: a meta-analysis. Epidemiology 2011; 22:344.
  135. Tramacere I, Pelucchi C, Bagnardi V, et al. A meta-analysis on alcohol drinking and esophageal and gastric cardia adenocarcinoma risk. Ann Oncol 2012; 23:287.
  136. Lauby-Secretan B, Scoccianti C, Loomis D, et al. Body Fatness and Cancer--Viewpoint of the IARC Working Group. N Engl J Med 2016; 375:794.
  137. 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.
  138. Turati F, Tramacere I, La Vecchia C, Negri E. A meta-analysis of body mass index and esophageal and gastric cardia adenocarcinoma. Ann Oncol 2013; 24:609.
  139. Lagergren J, Bergström R, Nyrén O. Association between body mass and adenocarcinoma of the esophagus and gastric cardia. Ann Intern Med 1999; 130:883.
  140. Cook MB, Greenwood DC, Hardie LJ, et al. A systematic review and meta-analysis of the risk of increasing adiposity on Barrett's esophagus. Am J Gastroenterol 2008; 103:292.
  141. Corley DA, Kubo A, Levin TR, et al. Abdominal obesity and body mass index as risk factors for Barrett's esophagus. Gastroenterology 2007; 133:34.
  142. Lanuti M, Liu G, Goodwin JM, et al. A functional epidermal growth factor (EGF) polymorphism, EGF serum levels, and esophageal adenocarcinoma risk and outcome. Clin Cancer Res 2008; 14:3216.
  143. Newton M, Bryan R, Burnham WR, Kamm MA. Evaluation of Helicobacter pylori in reflux oesophagitis and Barrett's oesophagus. Gut 1997; 40:9.
  144. Loffeld RJ, Ten Tije BJ, Arends JW. Prevalence and significance of Helicobacter pylori in patients with Barrett's esophagus. Am J Gastroenterol 1992; 87:1598.
  145. Csendes A, Smok G, Cerda G, et al. Prevalence of Helicobacter pylori infection in 190 control subjects and in 236 patients with gastroesophageal reflux, erosive esophagitis or Barrett's esophagus. Dis Esophagus 1997; 10:38.
  146. Goldblum JR, Vicari JJ, Falk GW, et al. Inflammation and intestinal metaplasia of the gastric cardia: the role of gastroesophageal reflux and H. pylori infection. Gastroenterology 1998; 114:633.
  147. Xia HH, Talley NJ. Helicobacter pylori infection, reflux esophagitis, and atrophic gastritis: an unexplored triangle. Am J Gastroenterol 1998; 93:394.
  148. Labenz J, Blum AL, Bayerdörffer E, et al. Curing Helicobacter pylori infection in patients with duodenal ulcer may provoke reflux esophagitis. Gastroenterology 1997; 112:1442.
  149. Vicari JJ, Peek RM, Falk GW, et al. The seroprevalence of cagA-positive Helicobacter pylori strains in the spectrum of gastroesophageal reflux disease. Gastroenterology 1998; 115:50.
  150. Ye W, Held M, Lagergren J, et al. Helicobacter pylori infection and gastric atrophy: risk of adenocarcinoma and squamous-cell carcinoma of the esophagus and adenocarcinoma of the gastric cardia. J Natl Cancer Inst 2004; 96:388.
  151. Rokkas T, Pistiolas D, Sechopoulos P, et al. Relationship between Helicobacter pylori infection and esophageal neoplasia: a meta-analysis. Clin Gastroenterol Hepatol 2007; 5:1413.
  152. Whiteman DC, Parmar P, Fahey P, et al. Association of Helicobacter pylori infection with reduced risk for esophageal cancer is independent of environmental and genetic modifiers. Gastroenterology 2010; 139:73.
  153. Lagergren J, Bergström R, Adami HO, Nyrén O. Association between medications that relax the lower esophageal sphincter and risk for esophageal adenocarcinoma. Ann Intern Med 2000; 133:165.
  154. Corley DA, Levin TR, Habel LA, Buffler PA. Barrett's esophagus and medications that relax the lower esophageal sphincter. Am J Gastroenterol 2006; 101:937.
  155. Freedman J, Ye W, Näslund E, Lagergren J. Association between cholecystectomy and adenocarcinoma of the esophagus. Gastroenterology 2001; 121:548.
  156. Suzuki H, Henry E, McElroy K, et al. In Barrett's esophagus, acid reflux generates high luminal concentrations of nitric oxide from dietary nitrate (abstract). Gastroenterology 2003; 124(Suppl):A32.
  157. Suzuki H, Iijima K, Moriya A, et al. Conditions for acid catalysed luminal nitrosation are maximal at the gastric cardia. Gut 2003; 52:1095.
  158. Iijima K, Grant J, McElroy K, et al. Novel mechanism of nitrosative stress from dietary nitrate with relevance to gastro-oesophageal junction cancers. Carcinogenesis 2003; 24:1951.
  159. Terry P, Lagergren J, Ye W, et al. Inverse association between intake of cereal fiber and risk of gastric cardia cancer. Gastroenterology 2001; 120:387.
  160. Mayne ST, Risch HA, Dubrow R, et al. Nutrient intake and risk of subtypes of esophageal and gastric cancer. Cancer Epidemiol Biomarkers Prev 2001; 10:1055.
  161. Bo Y, Lu Y, Zhao Y, et al. Association between dietary vitamin C intake and risk of esophageal cancer: A dose-response meta-analysis. Int J Cancer 2016; 138:1843.
  162. Kubo A, Levin TR, Block G, et al. Dietary antioxidants, fruits, and vegetables and the risk of Barrett's esophagus. Am J Gastroenterol 2008; 103:1614.
  163. Liao LM, Vaughan TL, Corley DA, et al. Nonsteroidal anti-inflammatory drug use reduces risk of adenocarcinomas of the esophagus and esophagogastric junction in a pooled analysis. Gastroenterology 2012; 142:442.
  164. Heath EI, Canto MI, Piantadosi S, et al. Secondary chemoprevention of Barrett's esophagus with celecoxib: results of a randomized trial. J Natl Cancer Inst 2007; 99:545.
  165. MacDonald WC, MacDonald JB. Adenocarcinoma of the esophagus and/or gastric cardia. Cancer 1987; 60:1094.
  166. Kubo A, Corley DA. Marked multi-ethnic variation of esophageal and gastric cardia carcinomas within the United States. Am J Gastroenterol 2004; 99:582.
  167. Hölscher AH, Bollschweiler E, Schneider PM, Siewert JR. Prognosis of early esophageal cancer. Comparison between adeno- and squamous cell carcinoma. Cancer 1995; 76:178.
  168. Dawsey SM, Wang GQ, Weinstein WM, et al. Squamous dysplasia and early esophageal cancer in the Linxian region of China: distinctive endoscopic lesions. Gastroenterology 1993; 105:1333.
  169. Acosta MM, Boyce HW Jr. Chromoendoscopy--where is it useful? J Clin Gastroenterol 1998; 27:13.
  170. Meltzer SJ. The molecular biology of esophageal carcinoma. Recent Results Cancer Res 1996; 142:1.
  171. Thorban S, Roder JD, Nekarda H, et al. Immunocytochemical detection of disseminated tumor cells in the bone marrow of patients with esophageal carcinoma. J Natl Cancer Inst 1996; 88:1222.
  172. Cameron AJ, Lomboy CT, Pera M, Carpenter HA. Adenocarcinoma of the esophagogastric junction and Barrett's esophagus. Gastroenterology 1995; 109:1541.
  173. Paraf F, Fléjou JF, Pignon JP, et al. Surgical pathology of adenocarcinoma arising in Barrett's esophagus. Analysis of 67 cases. Am J Surg Pathol 1995; 19:183.
  174. Johansson J, Johnsson F, Walther B, et al. Adenocarcinoma in the distal esophagus with and without Barrett esophagus. Differences in symptoms and survival rates. Arch Surg 1996; 131:708.
  175. Lieberman MD, Shriver CD, Bleckner S, Burt M. Carcinoma of the esophagus. Prognostic significance of histologic type. J Thorac Cardiovasc Surg 1995; 109:130.