Cancer Research UK : Oesophageal Cancer Risk Factors

Oesophageal Cancer Risk Factors

This page presents information on the risk factors for oesophageal cancer, including for squamous cell carcinoma (SCC), adenocarcinoma (AC), and for both squamous cell carcinoma and adenocarcinoma.

There are well established risk factors for both types of oesophageal tumour.1A few risk factors probably account for the majority of cases.

American data suggest that smoking, higher body mass index (BMI), low intake of fresh fruit and vegetables and gastro-oesophageal reflux are responsible for an estimated 79% of adenocarcinomas; while tobacco consumption, excess alcohol consumption and low fruit and vegetable intake are estimated to cause 89% of squamous cell carcinomas (SCC).2

Tobacco consumption whether by smoking cigarettes, cigars or pipes or by chewing increases the risk of both SCC and AC, although the effect is stronger for SCC.

Risk factors for squamous cell carcinoma of the oesophagus (SCC)

Tobacco and alcohol, acting independently and together, are the main risk factors for SCC of the oesophagus in western countries. The quantity of cigarettes smoked and the duration of smoking appear to be directly related to risk: risk declines on smoking cessation and falls to that of a non-smoker 10 or more years after giving up.3

Alcohol multiplies the effect of tobacco consumption.4 Data from Sweden was used to estimate the effect of smoking and alcohol on the risk for SCC and AC as shown in Figure 4.1.5

Figure 4.1: The effect of tobacco smoking, alcohol and bodyweight on the risk of SCC and AC of the oesophagus

Download this chart (26.5KB)

Heavy smoking and drinking increased the risk by 20-fold for SCC of the oesophagus, although odds ratios as high as 50 and 130 for combined categories of heavy drinking and smoking have been reported in studies carried out in Italy and South America.3, 6

Alcohol consumption increases the risk of SCC independently of smoking (Figure 4.1). Risk increases at moderate levels of alcohol consumption with a meta-analysis estimating an 18% increase in risk for each additional 100g/week of alcohol consumption.4

Risk increases significantly with higher alcohol consumption: a recent European case-control study reported an odds ratio of almost 25 in men drinking 84 or more drinks a week.3 However, in a recent UK case-control study of SCC in women, no association was found with alcohol although there was a significant association with smoking.7

A diet low in fruit and vegetables is the third main risk factor for SCCof the oesophagus in developed countries. A recent meta-analysis of case-control and cohort studies reported a significant reduction in risk with higher consumption of fruit and a non-significant protective role of vegetable consumption.8 However, in contrast to adenocarcinoma, there is no association between obesity and SCC.

Although diet, smoking and alcohol explain the majority of oesophageal SCC in developed countries, a number of other conditions may explain a small proportion of cases: in high risk areas these factors may be responsible for a higher proportion.

Certain rare conditions such as Tylosis, an autosomal dominant inherited condition associated with palmoplantar keratosis (thickening of the skin on the palms of the hands and soles of the feet) and Plummer-Vinson syndrome (a condition in which iron deficiency anaemia, glossitis - inflammation of the tongue - and dysphagia are associated) are linked with an increased risk of SCC.

Patients with untreated achalasia (a condition in which the cardiac sphincter malfunctions) and coeliac disease (a disorder usually characterised by sensitivity to dietary gluten, small intestinal mucosal damage and malabsorption) also have an increased risk. A possible link with human papillomavirus (HPV) has also been reported.9

At least 15% of tumours analysed worldwide with polymerise chain reaction have been positive for HPV DNA. The detection rate is much higher in high risk areas such as China and Iran.10

Early studies in the high risk areas around northern Iran and in China, identified additional risk factors such as opium use, nutritional deficiences (eg zinc) in addition to a diet deficient in fruit and vegetables, specific foods which contain high levels of mycotoxins and nitrosamines and thermal injury from consumption of very hot beverages.11, 12

Temperature of food and drink may also be a factor in other countries including the UK.

A case-control study of women with SCC in England and Scotland found that the risk of this cancer was reduced by two-thirds in women who consumed tea and coffee warm rather than burning hot.7 However, a nationwide case-control study in Sweden reported no association between temperature of drinking hot beverages and oesophageal cancer.13

In the high risk areas of South America (northeastern Argentina, southern Brazil, Uruguay and Paraguay) an analysis of five case-control studies confirmed that the consumption of very hot drinks was associated with a 2- to 4-fold increased risk.14 In this same area the drinking of maté, a locally grown herbal infusion, was also positively associated with oesophageal cancer. The effect of maté was increased if drunk at high temperatures. 14, 15

Risk factors for squamous cell carcinoma (SCC) of the oesophagus and adenocarcinoma (AC) of the oesophagus

Risk of oesophageal cancer is increased in people who have had radiotherapy to the mediastinum for another primary cancer. A record linkage study carried out in the south east of England reported a two-fold increase in risk of oesophageal cancer in women treated with radiotherapy for breast cancer more than 15 years previously.16

A pooled analysis of studies from America and Europe reported a greatly increased risk of oesophageal cancer in people treated with radiotherapy for Hodgkin’s lymphoma, with an observed/expected ratio of 19.5 reported 20-24 years after a diagnosis with the first cancer.17

Use of non-steroidal anti-inflammatory drugs (NSAIDS) reduces risk of AC and SCC, with a recent meta-analysis reporting significant summary relative risks of 0.65 for any NSAID use and 0.51 for aspirin use.18

The predominance of male cases suggests that occupational exposures may play a role, but occupational risk factors have been difficult to study because of the confounding effect of smoking and alcohol use. Amongst other studies it has been suggested that exposure to trichlorethylene in the dry-cleaning industry and silica dust may increase risk but this is likely to account for only a very small number of cases.19, 20

Risk factors for adenocarcinoma (AC) of the oesophagus

One of the strongest risk factors for adenocarcinoma of the oesophagus is an acquired premalignant condition known as Barrett’s oesophagus or metaplasia (BM).

BM usually develops in adult life arising principally as a result of gastro-oesophageal reflux disease (GORD), although any insult, which causes distal oesophageal irritation, such as chemical injury, and medical conditions including scleroderma (disease of connective tissue which can affect multiple organs including the skin), achalasia and hiatus hernia, are also associated with metaplasia.

Genetic factors may occasionally play a role in a small proportion of BM as this lesion can exhibit familial clustering and occurs in twins.21. Short segment Barrett’s oesophagus, less than 3cm in length from the estimated GOJ, is frequently missed by endoscopists and is more prevalent than long segment Barrett’s mucosa.22

Inflammation of the oesophagus (oesophagitis) caused by GORD is a very common medical condition in Western countries with 30% of adults complaining of heartburn at least once per month.23,24

Forty per cent of patients will improve spontaneously, 50% will have persistent oesophagitis and around 10% will progress to BM.23,24

Between 0.5-2% of adults in western populations are thought to have BM.25 The risk of AC in people with BM is low in absolute terms with an annual risk of carcinoma of about 0.5-1% but this represents a risk which is 30-125 times higher than the general population.26

People with very long segments of Barrett’s oesophagus (8-10 cm) have an increased risk (1.7 times) of oesophageal cancer compared to people with shorter segments (3-8cm).27 Approximately 10-20% of individuals with Barrett’s oesophagus develop dysplasia including those with short segment Barrett’s oesophagus.28

The clinical risk factors for both Barrett’s metaplasia and its related adenocarcinoma are summarised in Table 4.1.29-41

Table 4.1: Clinical risk factors for Barrett's metaplasia and associated adenocarcinoma

Risk is highest in older, white, obese men experiencing severe symptoms of reflux over a long period. A strong dose-dependent relationship between body mass index (BMI) and AC has been found which is not the case for SCC.34 However, the precise way in which body fat raises risk is not yet certain.34

Anticholinergics and other drugs which relax the oesophageal sphincter are associated with increased risk of AC and this may be because they predispose to reflux.42

Drugs given to asthmatics such as β-agonists and aminophyllines also have the effect of relaxing the sphincter and this is the likely reason for the higher incidence of AC observed in asthmatics.43

The presence of helicobacter pylori may protect against the acidic effect of gastric reflux. Elimination of helicobacter pylori, which is known to reduce the risk of stomach cancer, can make acid suppression with proton pump inhibitors more difficult in GORD. While this effect is statistically significant it may not be clinically significant in the management of individual patients.

As yet none of the risk factors in Table 4.1, above, are sensitive or specific enough to identify accurately ‘high risk’ individuals.

References

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Oesophageal Cancer Risk Factors

Risk factors for squamous cell carcinoma of the oesophagus (SCC)

Risk factors for squamous cell carcinoma (SCC) of the oesophagus and adenocarcinoma (AC) of the oesophagus

Risk factors for adenocarcinoma (AC) of the oesophagus

References

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