Esophageal Cancer Prevention (PDQ®): Prevention - Health Professional Information [NCI]

Incidence and Mortality

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.[11] 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.[22] 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.[33] In contrast, the incidence of adenocarcinoma of the esophagus rapidly increased from the 1970s to the mid-1990s.[44]

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.[44]

References:

1. American Cancer Society: Cancer Facts and Figures 2024. American Cancer Society, 2024. Available onlineAvailable online. Last accessed June 21, 2024.
2. Surveillance Research Program, National Cancer Institute: SEER*Explorer: An interactive website for SEER cancer statistics. Bethesda, MD: National Cancer Institute. Available onlineAvailable online. Last accessed September 5, 2024.
3. Devesa SS, Blot WJ, Fraumeni JF: Changing patterns in the incidence of esophageal and gastric carcinoma in the United States. Cancer 83 (10): 2049-53, 1998.
4. Hur C, Miller M, Kong CY, et al.: Trends in esophageal adenocarcinoma incidence and mortality. Cancer 119 (6): 1149-58, 2013.

Squamous Cell Carcinoma of the Esophagus

Factors With Adequate Evidence of Increased Risk of Squamous Cell Carcinoma of the Esophagus

Smoking cigarettes and drinking alcohol

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%).[11,22] 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.[11] 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%).[33]

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).[11]

Factors With Adequate Evidence of Decreased Risk of Squamous Cell Carcinoma of the Esophagus

Chemoprevention

A prospective, placebo-controlled, esophagus chemoprevention study randomly assigned 610 high-risk Chinese patients.[44] 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.[55] 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.[66]

Aspirin and nonsteroidal anti-inflammatory drug (NSAID) use

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.[77] 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).[77]

References:

1. Oesophagus. In: World Cancer Research Fund, American Institute for Cancer Research: Food, Nutrition and the Prevention of Cancer: A Global Perspective. The Institute, 1997, pp 118-129.
2. Siemiatycki J, Krewski D, Franco E, et al.: Associations between cigarette smoking and each of 21 types of cancer: a multi-site case-control study. Int J Epidemiol 24 (3): 504-14, 1995.
3. Engel LS, Chow WH, Vaughan TL, et al.: Population attributable risks of esophageal and gastric cancers. J Natl Cancer Inst 95 (18): 1404-13, 2003.
4. Muñoz N, Wahrendorf J, Bang LJ, et al.: No effect of riboflavine, retinol, and zinc on prevalence of precancerous lesions of oesophagus. Randomised double-blind intervention study in high-risk population of China. Lancet 2 (8447): 111-4, 1985.
5. Muñoz N, Hayashi M, Bang LJ, et al.: Effect of riboflavin, retinol, and zinc on micronuclei of buccal mucosa and of esophagus: a randomized double-blind intervention study in China. J Natl Cancer Inst 79 (4): 687-91, 1987.
6. Yang GC, Lipkin M, Yang K, et al.: Proliferation of esophageal epithelial cells among residents of Linxian, People's Republic of China. J Natl Cancer Inst 79 (6): 1241-6, 1987.
7. Corley DA, Kerlikowske K, Verma R, et al.: Protective association of aspirin/NSAIDs and esophageal cancer: a systematic review and meta-analysis. Gastroenterology 124 (1): 47-56, 2003.

Adenocarcinoma of the Esophagus

Factors Associated With Increased Risk of Adenocarcinoma of the Esophagus

Gastroesophageal reflux disease (GERD)

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.[11] 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).[11] 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).[22] 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.[33] The intestinal-type epithelium of Barrett esophagus has a characteristic endoscopic appearance that differs from squamous epithelium.[44] Dysplasia in Barrett epithelium represents a neoplastic alteration of the columnar epithelium that may progress to invasive adenocarcinoma.[55]

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.

Interventions With Adequate Evidence of Decreased Risk of Adenocarcinoma of the Esophagus

Aspirin and NSAID use

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.[66] 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).[66]

Radiofrequency ablation in dysplastic Barrett esophagus

A randomized controlled trial [77] 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.[77]

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.

References:

1. Lagergren J, Bergström R, Lindgren A, et al.: Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. N Engl J Med 340 (11): 825-31, 1999.
2. Cook MB, Corley DA, Murray LJ, et al.: Gastroesophageal reflux in relation to adenocarcinomas of the esophagus: a pooled analysis from the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON). PLoS One 9 (7): e103508, 2014.
3. Spechler SJ, Goyal RK: The columnar-lined esophagus, intestinal metaplasia, and Norman Barrett. Gastroenterology 110 (2): 614-21, 1996.
4. Van Dam J, Brugge WR: Endoscopy of the upper gastrointestinal tract. N Engl J Med 341 (23): 1738-48, 1999.
5. Reid BJ, Blount PL, Rabinovitch PS: Biomarkers in Barrett's esophagus. Gastrointest Endosc Clin N Am 13 (2): 369-97, 2003.
6. Corley DA, Kerlikowske K, Verma R, et al.: Protective association of aspirin/NSAIDs and esophageal cancer: a systematic review and meta-analysis. Gastroenterology 124 (1): 47-56, 2003.
7. Shaheen NJ, Sharma P, Overholt BF, et al.: Radiofrequency ablation in Barrett's esophagus with dysplasia. N Engl J Med 360 (22): 2277-88, 2009.

Latest Updates to This Summary (10 / 31 / 2024)

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.

Incidence and MortalityIncidence and Mortality

Revised texttext 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.

This summary is written and maintained by the PDQ Screening and Prevention Editorial BoardPDQ Screening and Prevention Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ SummaryAbout This PDQ Summary and PDQ® Cancer Information for Health ProfessionalsPDQ® Cancer Information for Health Professionals pages.

About This PDQ Summary

Purpose of This Summary

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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This summary is reviewed regularly and updated as necessary by the PDQ Screening and Prevention Editorial BoardPDQ Screening and Prevention Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

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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-pdqhttps://www.cancer.gov/types/esophageal/hp/esophageal-prevention-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389392]

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Last Revised: 2024-10-31