Environmental Causes of Esophageal Cancer

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This article reviews the environmental risk factors and predisposing conditions for the two main histologic types of esophageal cancer. Tobacco smoking, excessive alcohol consumption, drinking maté, low intake of fresh fruits and vegetables, achalasia, and low socioeconomic status increase the risk of esophageal squamous cell carcinoma. Results of investigations on other potential risk factors, including opium consumption, intake of hot drinks, eating pickled vegetables, poor oral health, and exposure to human papillomavirus, polycyclic aromatic hydrocarbons, N-nitroso compounds, acetaldehyde, and fumonisins are discussed. Gastroesophageal reflux, obesity, tobacco smoking, hiatal hernia, achalasia, and, probably, absence of H pylori in the stomach increase the risk of esophageal adenocarcinoma. Results of studies investigating other factors are also discussed.

Section snippets

Tobacco Use

As early as 1979, the US Surgeon General19 reported that, “Cigarette smoking is a significant causal factor in the development of EC. The risk … increases with the amount smoked.” The 1989 Surgeon General report20 added that: “The proportion of EC deaths attributable to tobacco use in the United States is estimated to be 78 percent for men and 75 percent for women.” Since the publication of these reports, a large number of case-control and cohort studies have confirmed these statements.

Low Intake of Fresh Fruit and Vegetables

Low intake of fresh fruit and vegetables has long been considered as a possible risk factor for EC. A review of the evidence by World Cancer Research Fund and American Institute for Cancer Research (WCRF-AICR),103 published in 2007, identified four cohort studies (all from China), 36 case-control studies, and seven ecological studies of the association of fruit intake and EC. The large majority of these studies found inverse associations between intake of fruits, especially citrus fruits, and

Nonsteroidal Anti-Inflammatory Drugs

A meta-analysis of nine studies, published in 2003, concluded that aspirin and other NSAIDs reduced risk of EC in a dose-response manner. More frequent use was associated with lower risk, with an overall risk reduction of approximately 40%.122 This meta-analysis also showed that these drugs had similar inverse associations with ESCC and EA. Several other studies published since then, mostly focused on EA, have shown similar results.123, 124, 125, 126, 127 This association may be due to reverse

Helicobacter Pylori

Helicobacter pylori is a known cause of noncardia gastric adenocarcinoma and gastric mucosa-associated lymphoid tissue lymphoma.140 The association of this gram-negative bacterium with other gastrointestinal cancers, most notably EC, has also been evaluated in several studies.

H pylori has shown a consistent pattern of association with EA. The large majority of epidemiologic studies have found a protective association, and the results of three recently published meta-analyses showed that H pylori

Polycyclic Aromatic Hydrocarbons

PAHs are produced during incomplete combustion of organic materials. The major sources of exposure to PAHs are smoking tobacco,42 eating charbroiled meat and other food products,171 air pollution,172 and occupational exposure.173

PAHs have long been suspected to be human carcinogens. In 1755, Percivall Pott174 found that exposure to soot, which contains high amounts of PAHs, causes scrotal cancers in chimney sweeps. In 1915, Yamagiwa, a Japanese pathologist, induced cancer for the first time by

Gastroesophageal Acid Reflux

Symptomatic gastroesophageal acid reflux is perhaps the strongest known risk factor for EA. In a population-based case-control study from Sweden, Lagergren and colleagues205 showed a strong dose-response association of both frequency and duration of reflux with EA. In this study, any reflux was associated with approximately eight-fold increased risk, but risk was increased up to 20-fold in those with very frequent and severe reflux.205 Several other studies published since then have confirmed a

Occupational exposure

EC is generally not considered an occupational cancer. However, several studies have suggested that occupational exposure to asbestos could increase EC risk between 2-fold and 16-fold.241, 242, 243, 244, 245 Other studies have found increased EC risk in relation to occupational exposure to silica.246, 247, 248, 249 However, other studies have shown no or only very slight increased risk with these occupational exposures. For example, Kang and colleagues250 found only an 8% increased risk of EC

Low socioeconomic status

It has long been known that EC is a disease of the poor and the socially disadvantaged. In his 1939 paper, Watson4 writes “… it should be noted that a large percentage of the patients in this series [of 771 EC cases] are … of a station in life definitely below average, and further, that 9 out of 10 patients with this disease are in the lower middle class socially, and on the whole financially insecure.”

Since then, a large number of epidemiologic studies have confirmed that EC risk is higher in

Summary

Over the past century, a large number of factors have been tested for their potential association with EC risk. Whereas older studies mainly investigated the etiology of ESCC, the newer studies in Western countries have also investigated the causes of EA.

The results of these studies have established excessive use of alcohol, tobacco use, low intake of fresh fruit and vegetables, low SES, and drinking maté as risk factors for ESCC. Also, certain physiologic or pathologic conditions, such as

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    Writing this review article was supported by the Intramural Research Program of the National Cancer Institute, National Institutes of Health.

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