Note: The Overview section summarizes the published evidence on this topic. The rest of the summary describes the evidence in more detail.
Other PDQ summaries on Esophageal Cancer Screening; Esophageal Cancer Treatment; and Levels of Evidence for Cancer Screening and Prevention Studies are also available.
Smoking and drinking alcohol may account for roughly 90% of esophageal squamous cell carcinoma cases in Western countries like the United States.[1] Gastroesophageal reflux/Barrett esophagus is associated with an increased risk of esophageal adenocarcinoma. Other factors that may explain the increased risk of adenocarcinoma of the esophagus include obesity [2] and the use of medications such as anticholinergics that can predispose to gastroesophageal reflux disease (GERD) by relaxing the lower esophageal sphincter.[3]
Based on solid evidence, smoking cigarettes and drinking alcohol increases the risk of esophageal squamous cell carcinoma. Smoking and drinking alcohol may account for roughly 90% of esophageal squamous cell carcinomas in Western countries like the United States.[1]
Magnitude of Effect: Increased risk, moderate magnitude.
Based on solid evidence, avoidance of tobacco and alcohol would decrease the risk of squamous cell carcinoma.[1,4]
Magnitude of Effect: Large positive benefit.
Based on fair evidence, epidemiological studies have found that aspirin or NSAID use is associated with decreased risk of developing or dying from esophageal cancer (odds ratio [OR], 0.57; 95% confidence interval [CI], 0.47–0.71).[5]
Magnitude of Effect: Small positive.
Based on solid evidence, harms of NSAID use include upper gastrointestinal bleeding and serious cardiovascular events, such as myocardial infarction, heart failure, hemorrhagic stroke, and renal impairment.
Magnitude of Effect: Increased risk, small magnitude.
Based on fair evidence, an association exists between GERD and adenocarcinoma, particularly if the GERD is long-standing and symptoms are severe.[6,7] In a case-control study from Sweden, the OR for patients with recurrent reflux symptoms was 7.7, while the OR for patients with long-standing and severe symptoms was 43.5 (95% CI, 18.3–103.5).[8] A meta-analysis of 1,128 individuals with esophageal adenocarcinoma from five case-control studies reported statistically significant increases in risk with recurrent heartburn (OR, 4.6; 95% CI, 3.3–6.6), regurgitation (OR, 4.6; 95% CI, 3.4–6.1), or both (OR, 4.8; 95% CI, 3.4–6.8). Daily heartburn and regurgitation was associated with an eightfold increase in risk (OR, 8.0; 95% CI, 4.5–14.0).[7]
It is unknown whether elimination of gastroesophageal reflux by surgical or medical means will reduce the risk of adenocarcinoma of the esophagus.[8,9]
Magnitude of Effect: Unknown.
Based on fair evidence, epidemiological studies have found that aspirin or NSAID use is associated with decreased risk of developing or dying from esophageal cancer (OR, 0.57; 95% CI, 0.47–0.71).[5,10]
Magnitude of Effect: Unknown magnitude.
Based on solid evidence, harms of NSAID use include upper gastrointestinal bleeding and serious cardiovascular events, such as myocardial infarction, heart failure, hemorrhagic stroke, and renal impairment.
Magnitude of Effect: Increased risk; small magnitude.
A randomized controlled trial has found that radiofrequency ablation of Barrett esophagus with severe dysplasia may lead to eradication of both dysplasia and intestinal metaplasia and a reduced risk of disease progression.[11]
Magnitude of Effect: Impact on cancer mortality not known.
Based on solid evidence, harms of radiofrequency ablation include esophageal stricture and requirement for dilatation and upper gastrointestinal hemorrhage but at low rates. It is possible that overdiagnosis and overtreatment of Barrett esophagus, particularly without severe dysplasia, could lead to a substantial number of harms.
Magnitude of Effect: The low rates of esophageal stricture and requirement for dilatation and upper gastrointestinal hemorrhage may be an understatement of the risks if this practice is widely adopted by less-experienced physicians.
Two histological types account for most malignant esophageal neoplasms: adenocarcinoma and squamous cell carcinoma. The epidemiology of these types varies markedly. In the 1960s, squamous cell carcinomas comprised over 90% of all esophageal tumors. The incidence of esophageal adenocarcinomas has risen markedly for the past 2 decades; it is now more prevalent than squamous cell carcinomas in the United States and Western Europe, with most tumors located in the distal esophagus.[1]
In 2024, it is estimated that 22,370 Americans will be diagnosed with esophageal cancer and 16,130 will die of this disease. Of the new cases, it is estimated that 17,690 will occur in men and 4,680 will occur in women.[1] Incidence rates for esophageal cancer have been falling on average 0.4% each year from 2012 to 2021. Death rates have been falling on average 1.1% each year from 2013 to 2022. Incidence rates generally increase with age in all racial and ethnic groups. Incidence rates are higher in White men compared with Black men in all age groups. In women, incidence rates are higher in Black women through age 74 years, at which point the rates become higher in White women.[2] Death rates are higher for White men compared with Black men at all ages. In women, death rates are higher in Black women through age 69 years, at which point the rates become higher in White women.
Although the overall incidence of squamous cell carcinoma of the esophagus is declining, this histological type remains six times more likely to occur in Black men than in White men.[3] In contrast, the incidence of adenocarcinoma of the esophagus rapidly increased from the 1970s to the mid-1990s.[4]
Male sex is an important predictor of adenocarcinoma of the esophagus. The attributable risk is low enough in women that, although the risk from sex is not modifiable, other risk factors necessarily have limited impact.[4]
In the United States, squamous cell carcinoma of the esophagus is strongly associated with tobacco and alcohol abuse. The relative risk associated with tobacco use is 2.4, and the population attributable risk is 54.2% (95% confidence interval [CI], 3.0%–76.2%).[1,2] Retrospective cohort studies adjusted for tobacco use have shown a twofold to sevenfold increase in the risk of esophageal cancer in individuals with alcohol addiction compared with rates for the general population.[1] Case-control studies have also suggested a significantly increased risk of cancer of the esophagus associated with alcohol abuse.
In a multicenter, population-based, case-control study of 221 patients with esophageal squamous cell carcinoma and 695 controls, ever-smoking, alcohol consumption, and low fruit and vegetable consumption accounted for 56.9% (95% CI, 36.6%–75.1%), 72.4% (95% CI, 53.3%–85.8%), and 28.7% (95% CI, 11.1%–56.5%) of esophageal squamous cell carcinomas, respectively, with a combined population attributable risk of 89.4% (95% CI, 79.1%–95.0%).[3]
In China, where the overall prevalence of esophageal carcinoma is much higher than in the United States, esophageal cancer is associated with deficiencies of nutrients, such as retinol, riboflavin, alpha-carotene, beta-carotene, alpha-tocopherol, ascorbate and zinc, and with exposure to specific carcinogens (e.g., N-nitroso compounds).[1]
A prospective, placebo-controlled, esophagus chemoprevention study randomly assigned 610 high-risk Chinese patients.[4] Patients were aged 35 to 64 years and received either placebo or combined low-dose retinol (15 mg or 50,000 IU) plus riboflavin (200 mg) and zinc gluconate (50 mg) for 13.5 months. Standard histological evaluations (including two endoscopic biopsies) were conducted for 93% of all entered patients. Micronuclei from esophageal cells were obtained before therapy began and after the 13.5 months of treatment. Serum levels of vitamin A, beta-carotene, riboflavin, and zinc were obtained at 0, 2, and 13.5 months.
The second report of this study presented micronuclei frequency results.[5] A statistically significant reduction in the mean percentage of micronucleated esophageal cells occurred in the active-treatment group compared with the placebo group. The pattern of cell proliferation, another potential intermediate end point marker, also improved.[6]
A systematic review and meta-analysis of the association between aspirin and NSAID use and esophageal cancer identified two cohort and seven case-control studies published between 1980 and 2001.[7] Pooled results showed a protective association between aspirin/NSAID use and esophageal cancer (odds ratio [OR], 0.57; 95% CI, 0.47–0.71). The association with aspirin use was statistically significant (OR, 0.50; 95% CI, 0.38–0.66); the association with NSAIDs was borderline significant (OR, 0.75; 95% CI, 0.54–1.0). Aspirin/NSAID use was associated with lower risk of both adenocarcinoma (OR, 0.67; 95% CI, 0.51–0.87) and squamous cell carcinoma (OR, 0.58; 95% CI, 0.43–0.78).[7]
The most important epidemiological difference between squamous cell carcinoma and adenocarcinoma is the strong association between GERD and adenocarcinoma. The results of a population-based case-controlled study suggest that symptomatic gastroesophageal reflux is a risk factor for adenocarcinoma of the esophagus. The frequency, severity, and duration of reflux symptoms were positively associated with an increased risk of adenocarcinoma of the esophagus.[1] In a case-control study from Sweden, the OR was 7.7 for patients with recurrent reflux symptoms, while the odds ratio (OR) for patients with long-standing and severe symptoms was 43.5 (95% confidence interval [CI], 18.3–103.5).[1] A meta-analysis of 1,128 individuals with esophageal adenocarcinoma from five case-control studies reported statistically significant increases in risk with recurrent heartburn (OR, 4.6; 95% CI, 3.3–6.6), regurgitation (OR, 4.6; 95% CI, 3.4–6.1), or both (OR, 4.8; 95% CI, 3.4–6.8). Daily heartburn and regurgitation was associated with an eightfold increase in risk (OR, 8.0; 95% CI, 4.5–14.0).[2] The probable mechanism is that long-standing GERD is associated with the development of Barrett esophagus, a condition in which an abnormal intestinal-type epithelium replaces the stratified squamous epithelium that normally lines the distal esophagus; Barrett esophagus is considered a precursor of esophageal adenocarcinoma.[3] The intestinal-type epithelium of Barrett esophagus has a characteristic endoscopic appearance that differs from squamous epithelium.[4] Dysplasia in Barrett epithelium represents a neoplastic alteration of the columnar epithelium that may progress to invasive adenocarcinoma.[5]
A population-based cohort study in Sweden shows that patients with Barrett esophagus develop adenocarcinoma of the esophagus at about 1.2 cases per 1,000 person-years of follow-up monitoring, which is about 11.3 times higher than in the general population. Thus, while the relative risk may be elevated, the absolute risk is still not high. Furthermore, over half of the cases of adenocarcinoma of the esophagus are not associated with GERD symptoms.
A systematic review and meta-analysis of the association between aspirin and nonsteroidal anti-inflammatory drug (NSAID) use and esophageal cancer identified two cohort and seven case-control studies published between 1980 and 2001.[6] Pooled results showed a protective association between aspirin/NSAID use and esophageal cancer (OR, 0.57; 95% CI, 0.47–0.71). The association with aspirin use was statistically significant (OR, 0.50; 95% CI, 0.38–0.66); the association with NSAIDs was borderline significant (OR, 0.75; 95% CI, 0.54–1.0). Aspirin/NSAID use was associated with lower risk of both adenocarcinoma (OR, 0.67; 95% CI, 0.51–0.87) and squamous cell carcinoma (OR, 0.58; 95% CI, 0.43–0.78).[6]
A randomized controlled trial [7] assessed whether radiofrequency ablation (vs. sham ablation) could eradicate dysplastic Barrett esophagus and decrease the rate of neoplastic progression in patients with Barrett esophagus and dysplasia. Among patients with low-grade dysplasia, eradication of dysplasia occurred in 90.5% of the treatment group compared with 22.7% in the control group; in the high-grade dysplasia group, rates were 81.0% in the treatment group compared with 19.0% in the control group. Additionally, 77.4% of patients in the ablation group had complete eradication of intestinal metaplasia, compared with 2.3% in the control group. Patients in the ablation group had less disease progression, and although cancer was not a primary outcome because expected numbers were small, there were fewer cancers in the ablation group (1.2% vs. 9.3%; P = .045). The complication rate was relatively low; among 84 treated patients, there was one upper gastrointestinal hemorrhage and five strictures that were easily treated.[7]
This study suggests that the treatment of patients with Barrett esophagus and dysplasia may ablate Barrett esophagus and prevent disease progression, but the study provides only weak evidence about whether treatment reduces the outcome of esophageal cancer (because it was not designed to answer that question). Evidence from the study suggests that ablation does not simply coagulate and hide dangerous cells under the surface of the esophagus (those cells could later evolve to cancer). A question entirely separate from this study is whether patients should be screened for Barrett esophagus (this study focused on the treatment of patients with Barrett esophagus who had been identified as having dysplasia). Furthermore, the study does not discuss the net benefits and harms of an overall program of screening (e.g., screening of patients with GERD or certain GERD symptoms) and the surveillance of patients with Barrett esophagus. The potential for overdiagnosis and overtreatment may be considerable if physicians used results of this study to treat patients with Barrett esophagus and no dysplasia.
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Revised text to state that incidence rates for esophageal cancer have been falling on average 0.4% each year from 2012 to 2021. Death rates have been falling on average 1.1% each year from 2013 to 2022. In women, incidence rates are higher in Black women through age 74 years, at which point the rates become higher in White women.
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This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about esophageal cancer prevention. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.
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PDQ® Screening and Prevention Editorial Board. PDQ Esophageal Cancer Prevention. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/esophageal/hp/esophageal-prevention-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389392]
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