The two main types (i.e. squamous-cell carcinoma and adenocarcinoma) have distinct sets of risk factors. Squamous-cell carcinoma is linked to lifestyle factors such as smoking and alcohol. Adenocarcinoma has been linked to effects of long-term acid reflux. Tobacco is a risk factor for both types. Both types are more common in people over 60 years of age. Squamous-cell carcinoma The two major risk factors for esophageal squamous-cell carcinoma are tobacco (smoking or chewing) and alcohol. The combination of tobacco and alcohol has a strong synergistic effect. Some data suggest that about half of all cases are due to tobacco and about one-third to alcohol, while over three-quarters of the cases in men are due to the combination of smoking and heavy drinking. Risks associated with alcohol appear to be linked to its aldehyde metabolite and to mutations in certain related enzymes. Such metabolic variants are relatively common in Asia. Other relevant risk factors include regular consumption of very hot drinks (over 65 °C or 149 °F) and ingestion of caustic substances. High levels of dietary exposure to nitrosamines (chemical compounds found both in tobacco smoke and certain foodstuffs) also appear to be a relevant risk factor. Unfavorable dietary patterns seem to involve exposure to nitrosamines through processed and barbecued meats, pickled vegetables, etc., and a low intake of fresh foods. Other associated factors include nutritional deficiencies, low socioeconomic status, and poor oral hygiene. Chewing betel nut (areca) is an important risk factor in Asia. Physical trauma may increase the risk. This may include the drinking of very hot drinks. Adenocarcinoma<unk>  (lower part) as a result of Barrettʼs esophagus Male predominance is particularly strong in this type of<unk> , which<unk> curs about 7 to 10 times more frequently in men. This imbalance may be related to the characteristics and interactions of other known risk factors, including acid reflux and obesity. The long-term erosive effects of acid reflux (an extremely common condition, also known as gastroesophageal reflux disease or GERD) have been strongly linked to this type of cancer. Longstanding GERD can induce a change of cell type in the lower portion of the esophagus in response to erosion of its squamous lining. This phenomenon, known as Barrett's esophagus, seems to appear about 20 years later in women than in men, possibly due to hormonal factors. At a mechanistic level, in the esophagus there is a small HOXA13 expressing compartment that is more resistant to bile and acids as the normal squamous epithelium and that is prone to both intestinal differentiation as well as oncogenic transformation. Following GERD this HOXA13-expressing compartment outcompetes the normal squamous compartment, leading to the intestinal aspect of the esophagus and increased propensity to the development of<unk> . Having symptomatic GERD or bile reflux makes Barrett's esophagus more likely, which in turn raises the risk of further changes that can ultimately lead to adenocarcinoma. The risk of developing adenocarcinoma in the presence of Barrett's esophagus is unclear, and may in the past have been overestimated. Being obese or overweight both appear to be associated with increased risk. The association with obesity seems to be the strongest of any type of obesity-related cancer, though the reasons for this remain unclear. Abdominal obesity seems to be of particular relevance, given the closeness of its association with this type of cancer, as well as with both GERD and Barrett's esophagus. This type of obesity is characteristic of men. Physiologically, it stimulates GERD and also has other chronic inflammatory effects. Helicobacter pylori infection (a common<unk> currence thought to have affected over half of the world's population) is not a risk factor for esophageal adenocarcinoma and actually appears to be protective. Despite being a cause of GERD and a risk factor for gastric cancer, the infection seems to be associated with a reduced risk of esophageal adenocarcinoma of as much as 50%. The biological explanation for a protective effect is somewhat unclear. One explanation is that some strains of H. pylori reduce stomach acid, thereby reducing damage by GERD. Decreasing rates of H. pylori infection in Western populations over recent decades, which have been linked to less overcrowding in households, could be a factor in the concurrent increase in esophageal adenocarcinoma. Female hormones may also have a protective effect, as EAC is not only much less common in women but develops later in life, by an average of 20 years. Although studies of many reproductive factors have not produced a clear picture, risk seems to decline for the mother in line with prolonged periods of breastfeeding. Tobacco smoking increases risk, but the effect in esophageal adenocarcinoma is slight compared to that in squamous cell carcinoma, and alcohol has not been demonstrated to be a cause. Related conditions * Head and neck cancer is associated with second primary tumors in the region, including esophageal squamous-cell carcinomas, due to field cancerization (i.e. a regional reaction to long-term carcinogenic exposure). * History of radiation therapy for other conditions in the chest is a risk factor for esophageal adenocarcinoma. * Corrosive injury to the esophagus by accidentally or intentionally swallowing caustic substances is a risk factor for squamous cell carcinoma. * Tylosis with<unk>  is a rare familial disease with autosomal dominant inheritance that has been linked to a mutation in the RHBDF2 gene, present on chromosome 17: it involves thickening of the skin of the palms and soles and a high lifetime risk of squamous cell carcinoma. * Achalasia (i.e. lack of the involuntary reflex in the esophagus after swallowing) appears to be a risk factor for both main types of<unk> , at least in men, due to stagnation of trapped food and drink. * Plummer–Vinson syndrome (a rare disease that involves esophageal webs) is also a risk factor. * There is some evidence suggesting a possible causal association between human papillomavirus (HPV) and esophageal squamous-cell carcinoma. The relationship is unclear. Possible relevance of HPV could be greater in places that have a particularly high incidence of this form of the disease, as in some Asian countries, including China. * There is an association between celiac disease and<unk> . People with untreated celiac disease have a higher risk, but this risk decreases with time after diagnosis, probably due to the adoption of a gluten-free diet, which seems to have a protective role against development of malignancy in people with celiac disease. However, the delay in diagnosis and initiation of a gluten-free diet seems to increase the risk of malignancy. Moreover, in some cases the detection of celiac disease is due to the development of cancer, whose early symptoms are similar to some that may appear in celiac disease.
Esophageal cancer
Gastroesophageal reflux disease
Hypopharyngeal cancer
Esophageal spasm
Laryngeal cancer
Oropharyngeal cancer
Esophageal disease
Esophageal candidiasis