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Pancreatic cancer risk factors

The key risk factors for pancreatic cancer are discussed on this page. Pancreatic cancer risk is also strongly linked with age.1

Around 37% of pancreatic cancers in the UK are linked to lifestyle; 36% in males and 39% in females.

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.

Pancreatic 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.2 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.3 IARC and WCRF/AICR evaluations are the gold standard in cancer epidemiology. Their conclusions about pancreatic cancer risk factors are shown in Table 4.1.

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

Increase 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)
  • Tobacco, smokeless
  • Tobacco smoking
  • Body fatness
  • Alcohol
  • Thorium-232 and its decay products
  • X-radiation
  • Gamma-radiation
  • Abdominal fatness
  • Adult attained height
  • Red meat

-

  • Foods containing folate
  • Fruits
  • Physical activity

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Age

Pancreatic cancer is more common in older people.

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Tobacco

Tobacco smoking and smokeless tobacco are classified by IARC as causes of pancreatic cancer.2 An estimated 29% of pancreatic cancers in the UK are linked to tobacco smoking.1

Smoking

Pancreatic cancer risk is 2.2 times higher in current smokers compared with never-smokers, a pooled analysis showed.4 Risk increases with the number of cigarettes smoked per day, and duration of cigarette smoking, meta- and pooled analyses have shown.4,5

Pancreatic cancer risk in those who quit smoking 20 years ago is similar to that of never-smokers, a pooled analysis showed.4

Pancreatic cancer risk is increased to a similar extent in people who smoke cigars only and people who smoke cigarettes only, a pooled analysis showed.6 Pancreatic cancer risk is not associated with pipe-only smoking.6

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Environmental tobacco smoke

Pancreatic cancer risk is not associated with exposure to environmental tobacco smoke during childhood or adulthood, a meta-analysis showed.7

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Smokeless tobacco

Pancreatic cancer risk is around 60% higher among ever-users of snus, compared with snus never-users, a meta-analysis showed.8 However, pancreatic cancer risk is not associated with ever-use of smokeless tobacco overall, compared with never-use of any tobacco, a pooled analysis showed .6

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Overweight and obesity

Body fatness is classified by IARC and WCRF/AICR as a cause of pancreatic cancer.2,3 Abdominal fatness is classified by WCRF/AICR as a probable cause of pancreatic cancer.3 An estimated 12% of pancreatic cancers in the UK are linked to overweight and obesity.1

Pancreatic cancer risk increases by 10% per 5-unit BMI increase, a meta-analysis showed.9 Pancreatic cancer risk increases by 11% per 10cm waist circumference increase, and by 19% per 0.1-unit waist-to-hip ratio increment, this meta-analysis showed.9

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Alcohol

Alcohol consumption is classified by IARC as a possible cause of pancreatic cancer.2 WCRF/AICR make no judgment on the association between pancreatic cancer risk and alcohol consumption, due to limited evidence.3

Pancreatic cancer risk is 22% higher in people who consume 3 or more alcoholic drinks per day, and 60% higher in people who consume 5 or more alcoholic drinks per day, compared with those who consume less than 1 alcoholic drink per day, meta- and pooled analyses have shown.10,11 Pancreatic cancer risk is not associated with drinking fewer than 3 or 4 alcoholic drinks per day, meta- and pooled analyses have shown.10,11 The association may vary by sex, though evidence from pooled analyses of cohort studies remains unclear.12,13

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Ionising radiation

Thorium-232 and its decay products, X-radiation, and Gamma-radiation are classified by IARC as causes of pancreatic cancer.2

Pancreatic cancer mortality risk is not increased in atomic bomb survivors.14

An estimated 2% of pancreatic cancers in males in the UK, and 4% in females, are linked to radiotherapy for previous cancer.1,15

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Height

Greater adult attained height is classified by WCRF/AICR as a probable cause of pancreatic cancer.3 Height probably indicates genetic, environmental, hormonal and nutritional factors, rather than directly causing pancreatic cancer.3

Pancreatic cancer risk is not associated with adult height, meta- and pooled analyses have shown.16,17

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Diet

Red meat

Red meat is classified by WCRF/AICR as a possible cause of pancreatic cancer.3

Pancreatic cancer risk is 29% higher per 120g/day red meat intake in men, a meta-analysis showed.18 Pancreatic cancer risk is not associated with red meat intake in women.18 This sex difference may reflect overall lower red meat consumption in women.18

Pancreatic cancer risk may be increased with higher intake of fat from animal sources, though evidence remains unclear.19

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Medical conditions and treatments

Pancreatitis

Pancreatic cancer risk is almost threefold higher in people with chronic pancreatitis, compared with healthy controls, a pooled analysis showed.20 Pancreatic cancer risk is higher still shortly after pancreatitis diagnosis, probably because of increased investigative activity in this period and/or initial misdiagnosis of pancreatic cancer as pancreatitis.20

Pancreatic cancer risk is increased more than 50-fold in people with hereditary pancreatitis.21

Pancreatic cancer risk is 23% higher in people who have undergone cholecystectomy (gallbladder removal), a meta-analysis showed;22 pancreatitis is often associated with gallstone disease.

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Diabetes

Pancreatic cancer risk is 40-120% higher in diabetics compared with non-diabetics, meta- and pooled analyses show.23-27 Diabetes may be a cause or an early manifestation of pancreatic cancer.24

Among diabetics, pancreatic cancer risk may be decreased with metformin use,28-30 and increased with sulfonylureas31 or insulin32 use, compared with non-use of these medications. However, there is some evidence that pancreatic cancer risk is not associated with use of metformin31, insulin31 or thiazolidinediones.31,33

Pancreatic cancer risk is 58% higher in women with metabolic syndrome (characterised by overweight/obesity, ineffective insulin use, diabetes and hypertension), compared with the general population, a meta-analysis showed.34 Pancreatic cancer risk is not associated with metabolic syndrome in men.34

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Peptic ulcer

Pancreatic cancer risk is not associated with history of gastric or duodenal ulcer, a pooled analysis of case-control studies showed.35 However, risk was around doubled in male gastric ulcer patients in a cohort study.36

Pancreatic cancer risk is 6 times higher in people who have had gastrectomy (full/partial stomach removal) in the past two years.35 This probably reflects detection of prevalent cancer through increased investigative activity in this period, however post-operative bacteria growth may be implicated.35,37

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Blood group

Pancreatic cancer risk is 40% higher in people with group A blood, compared with other blood groups, a meta-analysis showed.38 Increased pancreatic cancer risk in people with group B or AB blood varies by H pylori infection prevalence in the population.38

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Previous cancer

Pancreatic cancer risk is higher in people with previous upper aerodigestive (e.g. oral, larynx), gynaecological (e.g. cervix, uterus, ovary), urological (e.g. bladder, kidney), or other (e.g. female breast, testis, stomach) cancer types, a pooled analysis showed.39 Pancreatic cancer risk varies with age at diagnosis of first cancer, and time since that diagnosis.39,40

This may reflect shared risk factors with the first cancer (e.g. smoking, reproductive factors, genetic conditions), or treatment for the first cancer (e.g. radiotherapy).39

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Family history and genetic conditions

Family history

Pancreatic cancer risk is 62-76% higher in people with a first-degree relative with the disease, meta- and pooled analyses have shown.41,42 Risk is higher in those with more first-degree relatives affected, or first-degree relatives diagnosed at a younger age.43 Pancreatic cancer risk is 45% higher in people with a first-degree relative with prostate cancer, a pooled analysis showed.41

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Genetic conditions

Pancreatic cancer risk is higher in people with the following rare genetic conditions, compared with the general population:43,44

These genetic syndromes explain a small proportion of familial pancreatic cancer.43,44

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Infections

Hepatitis

Pancreatic cancer risk is 20-60% higher in people with chronic hepatitis B infection, compared with hepatitis B-negative people, meta-analyses have shown.45-47,75

Hepatitis C infection may also increase pancreatic cancer risk, but evidence remains unclear.47-49

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Helicobacter Pylori (H.Pylori)

Pancreatic cancer risk is 56% higher in people in Europe with H pylori infection, compared with uninfected people, a meta-analysis showed.50

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Porphyromonas gingivalis/periodontal disease

Pancreatic cancer risk is higher in people with periodontal disease or tooth loss, cohort studies have shown.51,52 Porphyromonas gingivalis, a bacteria which causes periodontal disease, may be implicated.52

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Occupational exposures

An estimated 0.01% of pancreatic cancers in Great Britain are linked to occupational exposure to acrylamide (used in industry e.g. dye, fabric and paper manufacture; also found in foods).53

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

Decrease risk

Foods containing folate are classified by WCRF/AICR as probably protective against pancreatic cancer.3 Pancreatic cancer risk is 34% lower in people with the highest dietary folate intake, compared with those with the lowest intake, some meta-analyses have shown;54,55 however, no association was shown in a pooled analysis of cohort studies.56 Pancreatic cancer risk is not associated with supplemental folate intake (e.g. folic acid), a meta-analysis showed.55

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Fruits are classified by WCRF/AICR as possibly protective against pancreatic cancer.3 However, pancreatic cancer risk is not associated with fruit or vegetable intake, a meta-analysis showed.57 Pancreatic cancer risk may be lower in people with the highest citrus fruit intake, compared with those with the lowest, a meta-analysis showed.58 However, pancreatic cancer risk may be 22% higher per 25g/day fructose intake, a meta-analysis showed.59

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Physical activity of all types (occupational, household, transport, and recreational) is classified by WCRF/IACR as possibly protective against pancreatic cancer.3 Pancreatic cancer risk is 28% lower in people with the highest levels of total physical activity compared with those with the lowest, a meta-analysis showed.60 The association may be limited to occupational activity, not recreational.60,61

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Pancreatic cancer risk is 15% lower in women who have the highest number of children compared with those who have the lowest, a meta-analysis showed.62

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Pancreatic cancer risk is 25-27% lower in people with a history of allergy, meta- and pooled analyses have shown.63,64 However, pancreatic cancer risk is not associated with asthma.63,64

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No effect

WCRF/AICR make no judgment on the association between pancreatic cancer risk and intake of cereal (grains), dietary fibre, vegetables, pulses, soya, processed meat, poultry, fish, eggs, milk and dairy products, total fat, butter, plant oils, margarine, cholesterol, sugar (sucrose), tea (green or black), alcohol, nitrate and nitrite, total carbohydrate, folic acid supplements, vitamin C, vegetarianism, age at menarche, breastfeeding, or energy intake, due to limited evidence. Coffee is classified by WCRF/AICR as unlikely to have substantial effect on pancreatic cancer risk.3

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

  • Processed meat (though some evidence of risk increase)18
  • Aspirin or non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs)65,66
  • Sweetened carbonated drinks67
  • Occupational exposure to diesel exhaust68
  • Statins69
  • Dietary sucrose59
  • Dietary carbohydrates59
  • Fish or omega-3 fatty acids70
  • Dairy products (milk, cheese, cottage cheese, yogurt, ice-cream)71
  • Coffee72
  • Vitamin D (blood levels or dietary)73
  • Total fat (though some evidence of risk increase for specific types of dietary fat)19
  • Age at menarche, age at menopause74
  • Oral contraceptives, hormone replacement therapy74

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References for Pancreatic cancer risk factors

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Updated: 2 June 2014