Esophageal Cancer

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Causes and Risk Factors

Esophageal cancer is caused by a malignant change (mutation) in cells that comprise the lining of the esophagus. Esophageal tumors often invade the submucosa (i.e., layer of connective tissue) and then the muscular layer of the organ.

Age increases the risk for esophageal cancer and the disease is more common after the age of 50. Risk for developing cancer of the esophagus is about 3 times higher in men.

Other risk factors include medical conditions such as the following:

• Achalasia (rare disease that affects the muscles of the esophagus)
• Helicobacter pylori infection (associated with gastritis and peptic ulcer disease)
• Human papillomavirus (HPV) infection (may increase risk in high-incidence areas)
• Plummer-Vinson syndrome (also called Patterson-Kelly syndrome; characterized by anemia, brittle fingernails, and esophageal irritation)
• Prior history of other head and neck cancers
• Tylosis (rare, genetic, skin disorder that causes esophageal inflammation)

Recent studies indicate that esophageal cancer may have genetic (hereditary) risk factors. A number of genes have been identified that may increase the risk for the disease. Additional research is necessary to determine genetic risk factors for cancer of the esophagus.

Squamous Cell Carcinoma
In the United States, major risk factors for squamous cell carcinoma of the esophagus include heavy alcohol consumption, tobacco use (e.g., cigarette smoking, chewing tobacco), and previous caustic injury (e.g., ingesting lye). Risk for the disease is nearly 100 times greater when heavy alcohol use and smoking are combined.

In developing countries, major risk factors for this type of esophageal cancer include the following:

• Nutritional deficiency associated with lack of fresh fruits and vegetables
• Regular consumption of very hot beverages
• Regular ingestion of fermented vegetables
• Smoking and chewing tobacco

Environmental risk factors for squamous cell carcinoma include exposure to asbestos, perchlorethylene (common dry cleaning solvent), and fuel-burning appliances (e.g., space heaters, fireplaces, stoves).

Adenocarcinoma
Barrett's esophagus is the primary risk factor for adenocarcinoma of the esophagus. In this condition, tissue damage in the lining of the esophagus occurs as a result of chronic gastroesophageal reflux disease (GERD). About 10% of patients with GERD develop Barrett's esophagus and about 1% of these patients develop esophageal cancer. The most common symptom of GERD is frequent heartburn.

Obesity also is a risk factor for adenocarcinoma of the esophagus.

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