Stomach cancer - risk factors

This section contains information on risk factors for stomach cancer including Helicobacter pylori (H. pylori), smoking and alcohol, diet, medical conditions and medications, family history, radiation, occupation and physical activity.

Wide international variations in incidence and the dramatic falls seen across the developed world suggest that environmental factors are very important in gastric carcinogenesis. A study published in December 2011 estimated that, in the UK, around 78% of stomach cancer cases in men and 69% in women are linked to lifestyle and environmental factors.96 The proportion is higher in men than women due to higher prevalence of smoking among men in the past and linked to higher salt intake. In contrast, the proportion of cases linked to infection with H. pylori is higher in women.96

Evidence suggests a large number of risk factors for stomach cancer and it is very likely that its aetiology is multifactorial with the importance of different risk factors varying across populations and between individuals. The universal demographic factors are old age, male gender and low socio-economic status (The rising rates of adenocarcinoma of the gastric cardia have been principally associated with higher socio-economic status).

Stomach cancer risk factors

 
 

Helicobacter pylori and severe chronic atrophic gastritis

Infection with H. pylori is an important known risk factor for stomach cancer.

H. pylori is a common bacterial infection, with particularly high prevalence in the developing world. Crowded living conditions, poor hygiene, large families and low socio-economic status are all associated with high rates of H. pylori infection.

Prevalence of H. pylori infection has been declining in the UK, which may explain the falling incidence of distal stomach cancer. 1 Nonetheless, a study published in December 2011 estimated that around 32% of stomach cancer cases in the UK in 2010 were linked to infection with the bacterium.97

H. pylori infection doubles the risk of stomach cancer and the risk is almost three-fold among those infected with cagA-positive H. pylori strains. 2

H. pylori can induce the pre-cancerous lesion severe chronic atrophic gastritis (SCAG), the first step in the chain of events leading from normal intestinal mucosa to adenocarcinoma. Eradication of H. pylori through treatment can cause regression of precursor lesions. Findings from the European Prospective Investigation into Cancer (EPIC) suggest that SCAG increases the risk for cancers of the gastric cardia by around 11-fold and gastric non-cardia by 2.6 times. 94

Risk increases with the severity of gastric atrophy; people with severe multifocal atrophic gastritis have over 90 times increased risk of stomach cancer. 3

There is evidence that H. pylori eradication may help prevent gastric cancer, especially for people with peptic ulcer or pre-cancerous lesions. 4,5,60-62,77,78

Find out more on H. pylori.

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Tobacco and alcohol

Current smokers have around double the risk of stomach cancer compared to non-smokers. 6,7,11,12 Risk of stomach cancer falls to a similar level as never-smokers 10 years after quitting, 7,11 although for gastric cardia tumours specifically, it may take longer.80

The combined effect of smoking and H. pylori infection may be more than additive, with a greater than 10-fold increased risk of gastric cancer. 6,8 A study published in December 2011 estimated that around 22% of stomach cancers in the UK in 2010 were caused by smoking, with a higher proportion in men (around 26%) than women (around 15%).98 Nitrosamines are present in tobacco smoke, which may explain the increased risk. 9

A 40% increased risk of noncardia stomach cancer has been shown in a Swedish study for men chewing snus (a form of smokeless tobacco) who do not smoke.84

Results of a large Korean study suggest that heavy alcohol consumption increases risk of stomach cancer by a small amount in men who have never smoked.79 Results of another study suggest that heavy alcohol consumption may increase the risk of stomach cancer, but only in heavy smokers. 12 However, the majority of cohort studies have shown no effect of alcohol consumption on stomach cancer risk. 11,80-83

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Diet

High fruit and vegetable intake is associated with a reduced risk of gastric cancer in both cohort and case-control studies, 13,59 although there are some exceptions.75, 76 The EPIC study has shown that a Mediterranean-style diet reduces risk of stomach cancer. 69 In contrast, high intake of pickled vegetables in Japanese and Koreans has been shown to increase stomach cancer risk.73

High salt intake has been linked to risk of stomach cancer in a number of studies. 59 Intake of salt is difficult to measure, but one of the most recent prospective studies to examine the relationship between salt intake and stomach cancer in Japan showed that risk is three times higher among individuals with a salt intake of 16g/day or more, compared to intakes of less than 10g/day. The risk increase with high salt intake was limited to subjects with H.pylori infection and atrophic gastritis. 15

A study published in December 2011 estimated that, in 2010, around 37% of stomach cancer cases in men and around 34% in women in the UK were linked to people eating fewer than five portions a day (400g/day) of fruit and vegetables.99 Around 31% of cases in men and around 12% in women were linked to eating too much salt (6g/day or more).100 However, there is considerably more uncertainty about the links between stomach cancer and diet than, for example, about the link with smoking.96,99-100

It is not clear whether salt intake at current normal levels in European countries is linked to stomach cancer risk. A recent Danish study found no clear associations between salt intake and stomach cancer risk, although there were suggestive associations particularly for people with stomach disorders. 17 A Norwegian study found no association. 63

Heavily salted foods are often high in N-nitroso compounds. There is limited evidence that individuals with high intakes of N-nitrosodimethylamine (NDMA) or nitrite have an increased risk of stomach cancer. 19,20,21

Processed meat was linked to stomach cancer risk in a recent meta-analysis. 23 However, the World Cancer Research Fund deemed evidence on processed meat and stomach cancer limited. 59 Results from the EPIC study suggest an association with processed meat consumption in subjects that are infected with H. pylori. 26

There is growing evidence that overall meat intake is linked to stomach cancer risk, with a lower risk of stomach cancer shown for British vegetarians than meat-eaters,74 and the EPIC study showing an increased risk of stomach cancer with higher intake of red meat.26

 

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Medical conditions and medications

People diagnosed with gastro-oesophageal reflux disease (GORD) have a doubling in their risk of gastric cardia adenocarcinoma. 30 People who have undergone surgery to correct acid reflux have five times the risk of gastric cardia cancer. 31 People diagnosed with Barrett's oesophagus have an 18-fold risk increase. 33

H. pylori infection is linked with both gastric and duodenal ulcers but only gastric ulcer is associated with increased risk of stomach cancer, while the presence of duodenal ulcer appears to reduce risk. 35, 36 Patients who have undergone surgery for gastric ulcer have a lower risk than patients who have not received surgery. 36 Both conditions respond well to the elimination of H. pylori and are becoming less common in populations where the prevalence of H. pylori is declining. 37 Vagotomy - a surgical procedure to reduce acid secretion in the stomach - is associated with an increased risk of stomach cancer in the following 10 years. 36 People who have part of their stomach surgically removed (partial gastrectomy) for a benign stomach condition, such as an ulcer, have an increased risk of stomach cancer, which is highest 15 or more years after the operation. 65

Patients with pernicious anaemia - where there is severe gastric atrophy caused by an autoimmune condition - have two to three times increased risk of stomach cancer. 38,39

The risk of being diagnosed with stomach cancer is increased in people with a previous diagnosis of  oesophageal cancer, non-melanoma skin cancer, bowel cancer, non-Hodgkin’s lymphoma and thyroid cancer. In addition, men with a previous prostate, bladder, testis or breast cancer and women with a previous ovarian, cervical or breast cancer have an increased risk of stomach cancer. 40,41,64,85,86 Some of the risk increase may be related to treatment for the first cancer.

Regular use of aspirin and other non-steroidal anti-inflammatories (NSAIDS) is associated with a 30-40% reduction in risk of non-cardia stomach cancer. 42,67 Taking aspirin for at least five years has been shown to reduce risk of stomach cancer overall by around 60%.95 However, because of the potential adverse consequences of high intake of aspirin, such as gastrointestinal haemorrhage, it would not be recommended as a prophylactic measure.

One study has shown a reduced risk of stomach cancer in women who have taken hormone replacement therapy (HRT). 43

There is evidence that people with HIV/AIDS or who have undergone an organ transplant have a doubling in risk of stomach cancer. 66

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Bodyweight

 

High BMI (Body Mass Index) is linked to a two-fold increased risk of gastric cardia adenocarcinoma. 21,34 Most studies show an association between high BMI and gastric reflux symptoms, and this might provide an explanation for the association of this type of stomach cancer with BMI. 33 Around 13% of gastric cardia adenocarcinomas in the USA have been linked to people having a BMI of 27 or higher. 21

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Family history

Having a parent or sibling diagnosed with a stomach cancer increases risk 1.5-fold and three-fold respectively. 41

Some of this increased risk may be environmental, as studies have shown elevated risk in spouses of stomach cancer patients, 44 and that relatives of gastric cancer patients are twice as likely to be infected with H. pylori. 45

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Radiation

Studies of atomic bomb survivors show that risk of stomach cancer is directly related to dose of radiation, with almost double the risk in people most heavily exposed to radiation from the atomic bombs in Japan. 46 An increased risk has also been shown in people treated with radiotherapy for ankylosing spondylitis. 47 A study published in December 2011 estimated that around 1% of stomach cancers in men and around 2% in women in the UK in 2010 were linked to radiation.101 Nearly all of these cases were linked to diagnostic radiology or radiotherapy.101

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Occupation

Occupational exposure to metal dusts, 48-54 and other types of dusts - such as from mining or quarrying or stone cutting 52,55,56,87 - has been associated with an increased risk of gastric cancer in several studies. There is much more limited evidence, from a single study in each case, for an increased risk of stomach cancer with occupational exposure to diesel exhaust, radon (in uranium miners) and pesticides in farm workers.87-89 It has been estimated that around 3% of stomach cancers in men in the UK are linked to occupational exposures. For women, less than 0.5% of cases are thought to be linked to occupation. 102,103

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Physical activity

Results from the EPIC study show that people doing a greater amount of physical activity have a reduced risk of stomach cancer.68 Other studies have also supported a protective effect of physical activity.70,90-92 However, some studies have shown no effect, so more research is needed before we can be sure about the relationship of stomach cancer with physical activity, if any.71,72,93

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References for stomach cancer risk factors

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