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Stomach cancer risk factors

The key risk factors for stomach cancer are discussed on this page. Stomach cancer risk is also strongly linked with age and sex.

Around 75% of stomach cancers in the UK are linked to lifestyle: 78% in males and 69% in females.1

Generally the studies cited in this section are on stomach adenocarcinoma.

Meta-analyses and systematic reviews are cited where available, as they provide the best overview of all available research and most take study quality into account. Individual case-control and cohort studies are reported where such aggregated data are lacking.

 

Stomach cancer risk factors overview

The International Agency for Research on Cancer (IARC) evaluates evidence on the carcinogenic risk to humans of a number of exposures including tobacco, alcohol, infections, radiation, occupational exposures, and medications.6 The World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) evaluates evidence for other exposures including diet, overweight and obesity, and physical exercise.21 IARC and WCRF/AICR evaluations are the gold standard in cancer epidemiology. Their conclusions about stomach cancer risk factors are shown in Table 4.1.

Table 4.1: IARC and WCRF/AICR Evaluations of Stomach Cancer Risk Factors

Increases risk ('sufficient' or 'convincing' evidence) May increase risk ('limited' or 'probable' evidence) Decreases risk ('sufficient' or 'convincing' evidence) May decrease risk ('limited' or 'probable' evidence)
  • Helicobacter pylori (H Pylori
  • Working in rubber production
  • Tobacco smoking
  • X-radiation, gamma-radiation
  • Asbestos (all forms
  • Epstein-Barr virus
  • Inorganic lead compounds
  • Nitrate or nitritea
  • Pickled vegetables (traditional Asian)
  • Salted fish, Chinese-style
  • Salt
  • Salted/salty foods

-

  • Non-starchy vegetablesb
  • Allium vegetablesb
  • Fruitsb

a Ingested under conditions that result in endogenous nitrosation. b Not salted or pickled.

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Age and sex

Stomach cancer risk is strongly linked with age and sex.

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Helicobacter pylori (H Pylori)

Helicobacter Pylori (H Pylori) infection is classified by IARC as a cause of stomach cancer (Table 4.1).6 An estimated 32% of stomach cancers in the UK are linked to H Pylori infection.9

Stomach (non-cardia) cancer risk is 6 times higher in people with H Pylori infection, a pooled analysis showed.12 This relates to H Pylori status 10+ years prior to stomach cancer diagnosis, which is the most appropriate measure: negative H Pylori status shortly before stomach cancer diagnosis may reflect infection clearance due to the cancer itself, as H Pylori does not colonise cancer/pre-cancer cells.12

Stomach cancer risk is higher in CagA-positive H Pylori than in CagA-negative H Pylori.10,13 Stomach cancer risk among H Pylori-infected people is lower in those who receive H pylori eradication treatment, versus those who do not, a meta-analysis showed.16

Stomach (non-cardia) cancer risk is higher in people with H pylori infection probably because H Pylori can cause gastric atrophy, in a minority of infected people.10,12

H Pylori prevalence is falling in the UK, but it remains a problem in developing countries.7-9

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Tobacco

Smoking

Tobacco smoking is classified by IARC as a cause of stomach cancer (Table 4.1).6 An estimated 22% of stomach cancers in the UK are linked to smoking.1

Stomach cancer risk is 62% higher in male smokers compared with male never-smokers, meta-analyses have shown.18-20 Stomach cancer risk is 20% higher in female smokers compared with female never-smokers, meta-analyses have shown.18-20 Risk is higher in smokers for both cardia and non-cardia stomach cancer,19 and increases with number of cigarettes smoked per day.20 Stomach cancer risk is not higher in ex-smokers compared with never-smokers.20

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Diet

Pickled vegetables

Pickled vegetables (traditional Asian style) are classified by IARC as a cause of stomach cancer, based on limited evidence (Table 4.1).6

Stomach cancer risk is 28-56% higher in people with the highest intake of pickled foods, compared with those with the lowest, meta-analyses have shown.25,35

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Salt

Salt and salty foods are classified by WCRF/AICR as a probable cause of stomach cancer,21 and Chinese-style salted fish is classified by IARC as a probable cause of stomach cancer, based on limited evidence (Table 4.1).6 An estimated 24% of stomach cancers in the UK (31% in males and 12% in females) are linked to eating more than 6g of salt per day.36

Stomach cancer risk is 68% higher in people with high salt intake compared with those with low salt intake, a meta-analysis showed.113 Salt intake may increase the extent of H Pylori infection (the association between salt and stomach cancer risk may be limited to people with H Pylori infection38) and/or inflame/damage stomach tissue directly.37 Variability between studies may reflect differences in salt intake assessment or confounding by other components of high-salt foods/diets.39,40

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Meat

Processed, smoked, grilled or barbecued meat is classified by WCRF/IACR as a possible cause of stomach cancer, based on limited-suggestive evidence.21 Nitrate or nitrite ingested under conditions that result in endogenous nitrosation (the production of nitrosamines in the stomach) is classified by IARC as a probable cause of stomach cancer, based on limited evidence;6 some processed meats contain nitrites.

Stomach cancer risk is 37-45% higher in people with the highest processed meat intake compared with those with the lowest, a meta-analysis showed; however, the effect was not significant in cohort studies.41,11

Variability between studies may reflect differences by stomach cancer subsite or H Pylori status.45

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Occupational exposures

Working in rubber production is classified by IARC as a cause of stomach cancer (Table 4.1).6 Asbestos and inorganic lead compounds are classified by IARC as probable causes of stomach cancer, based on limited evidence (Table 4.1).6 An estimated 3% of stomach cancers in men in the UK, and 0.3% in women in the UK, are linked to occupational exposures (including working as a painter, as well as the IARC-classified factors).123

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Previous cancer

Stomach cancer risk is higher in male survivors of head and neck, oesophageal and larynx cancers, with no association with previous cancer in females, a cohort study in France showed.121

Stomach cancer risk is higher in female survivors of breast cancer, with no association with previous cancer in males, a cohort study in Australia showed.122

Stomach cancer risk is higher in testicular, cervical, or thyroid cancer survivors, which probably reflects the effects of radiotherapy treatment.54-57

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Ionising radiation

X radiation and gamma radiation are classified by IARC as causes of stomach cancer (Table 4.1).6 An estimated 1% of stomach cancers in the UK are linked to radiation (radiotherapy for a previous cancer, or diagnostic radiology).1

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Family history and genetic conditions

Family history

Stomach cancer risk is 2-10 times higher in people with a family history of the disease, a review of case-control studies showed.65

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Genetic conditions

1-3% of stomach cancers are linked to inherited stomach cancer predisposition syndromes, it is estimated.58

Stomach cancer risk is higher in people with BRCA2 mutation in their family.63 Stomach cancer risk is not associated with BRCA1 mutation.64

Stomach cancer occurs in around 70-80% of people with mutations in the E-cadherin (CDH1) gene, a cohort study showed.59

Stomach cancer risk is higher in people with hereditary non-polyposis colorectal cancer (HNPCC), Li-Fraumeni syndrome, familial adenomatous polyposis (FAP), or Peutz-Jeghers syndrome.61

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Alcohol

Stomach cancer risk is 20% higher per 50g+ (6+ units) per day of alcohol consumed, compared with non- or occasional drinking, a meta-analysis showed.70 Stomach cancer risk is not associated with moderate alcohol consumption, cohort studies have shown.66-69

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Medical conditions and treatments

Gastric atrophy

Stomach cancer risk is higher in people with gastric atrophy, and risk increases with the extent of the atrophy.11 Not all gastric cardia cancers are associated with gastric atrophy (and therefore H Pylori infection) – for those which resemble oesophageal adenocarcinomas, gastric atrophy may even be protective.14,15

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Reflux

Stomach (cardia) cancer risk is more than doubled in people with reflux or excess acid, case-control studies have shown;71,72 though some studies show no association.73

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Diabetes

Stomach cancer risk is 24% higher in diabetic males compared with non-diabetic males, and 90% higher in diabetic females compared with non-diabetic females, a meta-analysis showed; the association may be limited to populations in east Asia.108

Stomach cancer risk among diabetics may be lower in metformin users compared with non-users, a meta-analysis of cohort studies showed; however meta-analysis of RCTs showed no association.125

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Stomach surgery

Stomach cancer risk is more than doubled in people who had gastrectomy for stomach ulcer 20-30 years ago, a cohort study showed.85

Stomach acid levels may be lower after surgery, increasing H Pylori susceptibility.85,86

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Blood group

Stomach cancer risk is 20% higher in people with blood group A versus those with blood group O, a cohort study showed.88 The association may be limited to diffuse type stomach cancer.89

H Pylori susceptibility and response may vary by blood group.88

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Proton pump inhibitors (PPIs)

Stomach cancer risk is higher in people who have been prescribed proton pump inhibitors (PPIs) for stomach ulcer treatment, a cohort study showed.97 This probably reflects H Pylori infection (which causes stomach ulcers) rather than a direct effect of PPIs.

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Tamoxifen

Stomach cancer risk may be higher in tamoxifen users compared with non-users, a meta-analysis showed, but evidence remains mixed.98

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Immune system

Autoimmune conditions

Stomach cancer risk is around 7 times higher in people with pernicious anaemia compared with the general population, a meta-analysis showed.74

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Organ transplant

Stomach cancer risk is around twice higher in organ transplant recipients compared with the general population, a meta-analysis showed.84

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Other infections

Epstein-Barr virus (EBV)

Epstein-Barr virus (EBV) infection is classified by IARC as a probable cause of stomach cancer, based on limited evidence (Table 4.1).6 Around 9% of stomach cancers are EBV-positive, meta-analyses have shown.78

It is unclear how EBV infection is associated with increased stomach cancer risk.79,80

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Human immunodeficiency virus (HIV)

Stomach cancer risk is around twice higher in people with human immunodeficiency virus (HIV)/AIDS compared with the general population, a meta-analysis showed.84

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Overweight and obesity

Stomach (cardia) cancer risk is 20-68% higher in people who are overweight or obese (body mass index [BMI] 25+), meta-analyses have shown.101,102 Non-cardia stomach cancer risk is not associated with overweight and obesity, a meta-analysis showed.103

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Height

Stomach cancer death risk is 5% lower per 6.5cm height increment, a meta-analysis showed;109 the association may be limited to males.110

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Reproductive factors

Stomach cancer risk is not associated with age at menarche (first menstrual period), age at menopause, parity, age at first birth, or oral contraceptive use, a meta-analysis showed.98

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Hormone replacement therapy (HRT)

Stomach cancer risk in women is 22-23% lower in those who have ever taken hormone replacement therapy (HRT) compared with HRT never-users, meta-analyses have shown.98,99

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Physical activity

Stomach cancer risk is 13-28% lower in the most physically active people compared with the least, meta-analyses have shown.107,111,112,127

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Factors shown to decrease or have no effect on stomach cancer risk

Decrease

Non-starchy vegetables, allium vegetables, and fruits are classified by WCRF/AICR as probably protective against stomach cancer (Table 4.1).21 Pulses and dietary selenium are classified by WCRF/AICR as possibly protective against stomach cancer, based on limited-suggestive evidence.21

Stomach cancer risk is lower in people with the highest intake of the following foods versus those with the lowest, meta- and pooled analyses or systematic reviews have shown (note that associations for fruit and vegetables may be limited to case-control studies, not cohort studies, and may be limited to smokers26-30,32):

  • Fruit overall - 10-51% decreased risk.115,116 
  • Cruciferous vegetables - 19% decreased risk.117
  • Citrus fruits - 28% decreased risk.33
  • Allium vegetables (e.g. onions and garlic) - 46% decreased risk.34
  • Tomato products - 27% decreased risk.118
  • Selenium measured in blood or toenails - gastric cardia cancer risk around halved46 (no association for stomach cancer risk overall119).
  • Dietary fibre - 42% decreased risk120 (though may be limited to cereal fibre50).

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Stomach cancer risk is lower in users of the following medications, versus non-users, meta- and pooled analyses or systematic reviews have shown:

  • Aspirin – 29% decreased risk with use 4.5 times per week (no further benefit with more frequent use), 28% decreased risk with use for 12 years (greater protective effect with longer-term use); association limited to non-cardia stomach cancer.91
  • Statins - 16% decreased risk.94

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No effect

WCRF/AICR make no judgement on the association between stomach cancer risk and intake of cereals, dietary fibre, potatoes, nuts and seeds, herbs and spices, condiments, poultry, eggs, milk and dairy, fats and oils, sugars,fruit juice, coffee, tea, alcohol, dietary nitrate and nitrite, N-nitrosodimethylamine (note IARC classifies ingested nitrate or nitrite under conditions that result in endogenous nitrosation as a possible cause of cancer based on limited evidence6), thiamine, riboflavin, vitamin C, vitamin D, multivitamin/mineral supplements, calcium, iron, selenium supplements, and carotenoids, due to limited evidence.21

Stomach cancer risk is not associated with the following factors, meta- and pooled analyses or systematic reviews have shown:

  • Vegetables overall115 (although some evidence of risk decrease116).
  • Beta-carotene supplements (though some evidence of risk increase with high doses and in smokers and asbestos-exposed workers).47
  • Age at menarche.98
  • Parity.98
  • Age at first birth.98
  • Use of oral contraceptives.98
  • Age at menopause98 (though some evidence of higher risk with younger age at menopause, and with being post-menopausal versus pre-menopausal/menopausal104).
  • Smokeless tobacco.105,106
  • Tea (though some evidence of lower risk for women).124
  • Coffee.126

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Updated: 21 May 2014