Esophageal Cancer

The esophagus is the food pipe that connects the mouth to the stomach in which two main types of cancer can occur, squamous cell carcinoma and adenocarcinoma. Squamous cell carcinoma begins in flat cells that line the esophagus: adenocarcinoma in cells that make and release mucus and other fluids. Esophageal squamous cell carcinoma (ESCC) is the sixth highest cause of cancer deaths worldwide, the fourth highest in China and ranks seventh in the UK.

The incidence of esophageal cancer has risen over the last 35 years, for example, from 5 to 25 cases per 100,000 in the UK. In the USA and western Europe there has also been a shift in the major type with adenocarcinoma now being more prevalent than squamous cell carcinoma. The reasons for these shifts are unknown.

Gastric cardia adenocarcinoma (GCA) and distal gastric adenocarcinoma (DGA) bear similarities to ESCC. Cardia is the border between the esophagus and the stomach.

New cases/year World 2008: 481,000; [male: 326,000, female: 155,000];USA 2008: 16,640; UK 2007: 8,000 {includes adenocarcinoma and squamous cell carcinoma}
Deaths/year World 2008: 406,800; [male: 276,000, female: 130,000];USA 2010 (est)14,500; UK 2008: 7,610 {includes adenocarcinoma and squamous cell carcinoma}
Risk factors Squamous cell carcinoma:Marked worldwide variation. In Europe and North America main risk factors are heavy smoking and alcohol consumption. In some areas of China, central Asia and southern Africa nutritional deficiencies and consumption of pickled vegetables, nitrosamine-rich or mycotoxin-contaminated foods contribute. Chewing tobacco or betel quid also increase risk.

High incidence areas show familial aggregation, i.e. genetic susceptibility, and several loci have been identified in Chinese and Japanese populations.

Age, sex and race: Esophageal cancer is rare in people under the age of 45, more common in men than in women and in African-Americans than whites. More than 80% of new cases and deaths occur in developing countries.

Two rare conditions pre-dispose to squamous cell carcinoma: Tylosis, an inherited condition in which skin grows too thickly on the palms of the hands and soles of the feet, which carries a high risk. Plummer-Vinson syndrome, a rare form of anaemia due to a lack of iron, causes blockage of the esophagus.


Less clear but one of the strongest risk factors is Barrett’s esophagus, a pre-cancerous condition that often results from gastro-esophageal reflux disease although it can arise from any damage to the tissue. About one in ten cases of Barrett’s esophagus progress to esophageal adenocarcinoma.

Achalasia, a defect of the cardiac sphincter (the valve between stomach and esophagus) causes blockage of the esophagus and increases by 10-fold the risk of both main types of esophageal cancer.

There is evidence that some strains of Helicobacter pylori may reduce the risk of Barrett’s esophagus and adenocarcinoma but may increase the risk of squamous cell carcinoma.

Prolonged, heavy exposure to soot, metal or silica dust or vehicle exhaust may also increase risk.


Painful or difficult swallowing, weight loss, chest pain, hoarseness and cough. Diagnosis usually by endoscopy (a long thin tube with a light and camera inside).

Staging TNM tumour staging system is used. The number system may also be used:Stage 0: carcinoma in situ (CIS) or high grade dysplasia (abnormal cell changes in the lining of the esophagus). The subsequent stages correspond to the TNM system as shown:

Stage 1A (T1, N0, M0), 1B (T2, N0, M0).

Stage 2A (T3, N0, M0), 2B (T1 or T2, N1, M0).

Stage 3A: (T4a, N0, M0), (T3, N1, M0) or (T1 or 2, N2, M0), 3B (T3, N2, M0), 3C (T4a, N1 or 2, M0), (T4b, N any, M0) or (T any, N3, M0).

Stage 4 (T any, N any, M1).

Major gene mutations

P53, MSR1, ASCC1 and CTHRC1.


Surgery, radiotherapy and chemotherapy. For adenocarcinoma a common drug combination is epirubicin, cisplatin and 5-fluorouracil (ECF). For squamous cell carcinoma a common combination is cisplatin and 5FU.

Side effects

May include anaemia, nausea, diarrhoea, hair loss, mouth ulcers and fatigue. General suppression of the immune system and increased infection risk.


5-year survival rate after surgery: 30-50% (stage II disease), 10-25% (stage III disease).