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Causes and Risks

The exact causes of pancreatic cancer are not known but it is thought that age, smoking, obesity and a family history of pancreatic cancer or other rare genetic conditions increase your risk.

A study published in December 2011 estimated that, in the UK, around 36% of pancreatic cancers in men and 39% in women are linked to lifestyle factors including tobacco smoking and being overweight/obesity1


Risk of contracting pancreatic cancer:

The estimated lifetime risk of contracting pancreatic cancer is relatively low at 1 in 73 for men and 1 in 74 for women2

Risk

Male

Female

By Age 65  (%)

0.3

0.2

Lifetime risk (%)

1.4

1.4

Lifetime risk (1in X)

73

74

Pancreatic cancer affects men & women equally:

Ratio of male to female pancreatic cancer incidence, UK 2010* 3

Ratio of male to female pancreatic cancer mortality, UK 2010*:

* European age-standardised rates per 100,000 population.

Age is the biggest risk factor for pancreatic cancer:

Age is the most significant risk factor for pancreatic cancer. The risk is low up until the age of 50 when it increases sharply. The median age of diagnosis is 724

 

Age

% of patients

<20

0%

20-34

0.40%

35-44

2.40%

45-54

9.60%

55-64

18.9%

65-74

26.6%

75-84

29.5%

85+

12.5%

Pancreatic cancer can often be missed in younger patients

Although the peak incidence is in the 65-75 year age group, pancreatic cancer can occur from the age of 20 with rates rising significantly from 45 years.5

40 per cent of all patients diagnosed in England between 2005 and 2009 were under the age of 696

Smoking causes nearly 1 in 3 of all pancreatic cancers:

Smoking Cigarette smoking is the only confirmed environmental cause of pancreatic cancer.
A study in 2011 estimated that around 29 per cent of UK pancreatic cancer cases were caused by smoking7

Among the 250 known harmful chemicals in tobacco smoke, at least 69 can cause cancer by damaging the DNA and by changing important genes This can cause cells to multiply and grow out of control – causing cancerous tumours – see our What is Cancer? section for more information.

Risk of smokers vs. non-smokers

A study in 20064 looked at the risk of contracting pancreatic cancer in smokers versus never smokers in 82 independent studies from 1950 – 2007. They found that smokers have an increased risk of 74% of developing pancreatic cancer compared to those who have never smoked.

A European-wide study in 2012 showed that risk increased by 27 per cent for every five cigarettes smoked per day8

Quitting smoking can reduce your risk of contracting pancreatic cancer

Quitting smoking reduces the risk of developing and dying from cancer. However, it takes a number of years after quitting for the risk of cancer to start to decline. This benefit increases the longer a person remains smoke free

Some studies have estimated it can take up to 10 years before the risk begins to decline9 A European-wide prospective study in 2009 however, showed that risk is reduced to the levels of a non-smoker after just five years of cessation10

If you need help to stop smoking, please visit NHS Smoke Free, the NHS Stop Smoking Service.

Effects of passive smoking, cigars and snuff (snus):

The European (EPIC) study showed that passive smoking (or second-hand smoke) either in the home or at work can increase the risk of pancreatic cancer by 50 per cent11 and that children who are exposed daily to tobacco smoke have double the risk of contracting pancreatic cancer in later life.12

Pipe and cigar smoking increases risk by 50 per cent13 and it is thought that smokeless tobacco14 and moist snuff (also known as snus) use15 can increase risk.

 

Alcohol consumption and risk of pancreatic cancer

wineWhile there is an association with heavy alcohol consumption and pancreatitis (a benign disease which causes inflammation of the pancreas), there is no confirmed link between alcohol consumption and the risk of pancreatic cancer. 

A recent large nested case-control study in 2010 showed no risk increase, even at consumption of 60g/day or more of liquor (spirits), and found no association with beer or wine16

 

Obesity increases your risk of pancreatic cancer

Obesity increases your risk of pancreatic cancerIn 2007, the World Cancer Research Fund17 concluded, “the evidence that greater body fatness is a cause of pancreatic cancer is convincing”

Why could obesity increase pancreatic cancer risk?

The fat tissues in overweight people produce more hormones and growth factors than those in people of a healthy weight. High levels of some of these hormones, including insulin which is produced in the pancreas, can increase the risk of certain cancers including pancreatic cancer

A study in 2011 estimated that around 12 per cent of all pancreatic cancers in the UK are attributable to overweight and obesity.18

The Million Women Study19 found women with a BMI >27.5 had a 20-37 per cent increased risk of pancreatic cancer (compared to those with healthy BMI)((Donghui Li et al., (2009) Body Mass Index and Risk Age of Onset and Survival in Patients With Pancreatic Cancer JAMA 301(24): 2553-2562))

A study in 200820 found that obese women who carry most of their excess weight around the waist rather than hips are “70 per cent more likely to develop pancreatic cancer.”

The latest meta-analysis review on the evidence linking obesity and pancreatic cancer risk conducted by researchers at Imperial College, London and the University of Leeds has confirmed the hypothesis that “increased BMI and abdominal obesity are associated with increased pancreatic cancer risk.”21

This study found that there was an increased risk of pancreatic cancer in both men and women who have a BMI of 25 but that risk was more pronounced in those with a BMI of 35 or greater. Risk was shown to increase by 10 per cent for a five-point increase in BMI.

This study also confirmed that carrying your weight around your middle (have a high waist-to-hip ratio) increased risk.

Want to know if you have a healthy BMI? Use the NHS BMI Healthy Weight Calculator

Diabetes and risk of pancreatic cancer

Diabetes blood sugar testingApprox. 1% of diabetics over the age of 50 will be diagnosed with pancreatic cancer within 3 years of “first meeting the criteriafor diabetes”22

Type-II Diabetes (non-insulin dependent)

Type-II diabetes is widely considered to be associated with pancreatic cancer, but whether diabetes causes pancreatic cancer or the pancreatic cancer causes the diabetes is unclear.

A meta-analysis in 2005 reported a relative risk of 1.8 for pancreatic cancer in people with type II (non-insulin dependent) diabetes and found that individuals in whom diabetes had only recently been diagnosed (less than four years) had a 50 per cent greater risk of pancreatic cancer compared with individuals who had diabetes for greater or equaling five years.23 A nested case-control study also in 2005 reported results supporting this association.24

Type I diabetes and early-onset diabetes

A meta-analysis in 2007 showed that people with type I (insulin dependent), and early-onset diabetes have double the risk of pancreatic cancer.25

Diabetes drugs and pancreatic cancer risk

A meta analysis in 2012 showed that metformin, a tablet taken by diabetic patients is associated with a 62 per cent decrease in pancreatic cancer risk, compared with diabetics not receiving this medication, a meta-analysis in 2012 showed. The same study however found that another class of diabetes drug; sulfonylureas did not reduce risk although the results were not consistent between studies26

Using data from the General Practice Research Database, a study in 2012 found that there was a decreased risk of pancreatic cancer associated with metformin use but only in women.27

The same study also found that diabetes mellitus was associated with an increased risk of pancreatic cancer, but the risk was restricted to those with newly diagnosed diabetes (less than 2 years). This backs up the findings of other scientists that short-term diabetes mellitus is likely caused by pancreatic cancer

There are currently investigations into the merits of using diabetes as a potential biomarker for pancreatic cancer28 and it has been found that pancreatic cancer induced hyperglycemia (high blood glucose levels) can occur up to 24 months prior to the diagnosis for pancreatic cancer29

Pancreatitis and pancreatic cancer risk

It is estimated that one per cent of pancreatic cancer cases are linked to chronic pancreatitis30

Chronic pancreatitis is a condition causing chronic inflammation of the pancreas. As compared to acute pancreatitis, it is relatively rare, affecting only 0.1 in 10,000 people in the UK. The majority of cases are linked to heavy alcohol consumption.

Several different studies have shown an increased risk of pancreatic cancer in people suffering from pancreatitis with risk ratios that range from two to more than 20.3132

A pooled analysis study in 2012 showed that for those who had a diagnosis of pancreatitis at least two years previously, had three times the risk of developing pancreatic cancer. For those in the same group who were under the age of 65 that risk was four times.33

Hereditary pancreatitis

Hereditary pancreatitis runs in families and usually occurs at a young age, often before the age of 30. These patients have a risk that is 50-60 times greater than expected.34 The absolute risk that those suffering hereditary pancreatitis will develop pancreatic cancer by the age of 75 is approximately 50 per cent.35

Hereditary Pancreatic Cancer

Sometimes pancreatic cancer is found to run in a family due to faulty genes. It is thought that hereditary pancreatic cancer makes up approx. 5-10% of all cases. There is currently no genetic test available specifically for pancreatic cancer.

People with at least two first-degree relatives (mother, father, brother, sister) diagnosed with pancreatic cancer have almost double the risk of people without pancreatic cancer in their family of contracting the disease.36

Click here for more information on hereditary pancreatic cancer

Previous cancers and other conditions

Previous cancers:

An international multi-centre study was carried out using data from 13 cancer registries in 2006 which found that people are at higher risk of developing pancreatic cancer within 10 years of a diagnosis of cancer of the bladder, cervix, eye, gallbladder, larynx, lung, pharynx stomach and uterus and 10 years or later following a diagnosis of cancers of the breast, bladder, cervix, colon, eye, gallbladder, kidney, ovary, stomach, testis, uterus, as well as Hodgkin’s and non-Hodgkin’s lymphomas.37

It is thought that some of these increased risks could be due to smoking, genetic links or to radiotherapy treatment for the first cancer.

Chron’s disease, gastric ulcers and gum disease

For people with a previous diagnosis for Chron’s disease, there is a 75 per cent increased risk of contracting pancreatic cancer.38

Patients with a gastric ulcer have an 80 per cent increased risk of pancreatic cancer. Those who have had an operation for the gastric ulcer have more than double the risk of the normal population.39

A study in 2008 identified that tooth loss and periodontal disease is associated with a 50 per cent risk of pancreatic cancer,40 while a study in 2010 found a doubling of risk of pancreatic cancer for periodontal disease.41 The biological mechanism for this association is not currently known.

Footnotes:

  1.  Parkin et al., (2011) The fraction of cancer attributable to lifestyle and environmental factors in the UK in 2010. British Journal of Cancer 105, S77 – S81 
  2. CRUK(2013) The Excess Burden of Cancer in Men in the UK, available online: http://publications.cancerresearchuk.org/downloads/Product/CS_REPORT_EXCESSBURDEN.pdf  
  3.  CRUK (2013) The Excess Burden of Cancer in Men in the UK, available online: http://publications.cancerresearchuk.org/downloads/Product/CS_REPORT_EXCESSBURDEN.pdf  
  4. Anderson, K et al., (2006) Pancreatic Cancer. In Cancer Epidemiology and Prevention. Schottenfeld, D Fraumeni, JF Jr., (eds.). New York: Oxford University Press pp 721-762. In Pancreatic Cancer (2010) Neoptolemous, J et al., (eds.) New York: Springer pp 5-19.  
  5. CRUK http://info.cancerresearchuk.org/cancerstats/types/pancreas/incidence/index.htm#age (accessed online, 24.02.2010)  
  6. Office for National Statistics Cancer Survival in England for patients diagnosed between 2005-2009 (and followed up to 2010) Published April 2012 Available online:

    http://www.ons.gov.uk/ons/rel/cancer-unit/cancer-survival-rates/2005-2009–followed-up-to-

    2010/stb-cancer-survival–2005-09-and-followed-up-to-2010.html (accessed 09/08/2012)  

  7. Parkin, D.M., Boyd, L., Walker, L.C. The fraction of cancer attributable to lifestyle and environmental factors in the UK in 2010. Summary and conclusions. Br J Cancer, 6 Dec 2011; 105 (S2):S77-S81; doi: 10.1038/bjc.2011.489  

  8. Leenders M, Chuang SC, Dahm CC et al. Plasma cotinine levels and pancreatic cancer in the EPIC cohort study. Int J Cancer 2012;131(4):997-1002. 
  9.  Fuchs, C.S., et al.,  A prospective study of cigarette smoking and the risk of pancreatic cancer. Arch Intern Med, 1996. 156(19): p. 2255-60 
  10. Vrieling, A., et al.,  Cigarette smoking, environmental tobacco smoke exposure and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition.Int J Cancer 2009. 
  11. Vrieling, A., et al.,  Cigarette smoking, environmental tobacco smoke exposure and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition.Int J Cancer 2009. 

  12. Chuan,S.C., Gallo, V., Michaud, D., et al.,  Exposure to environmental tobacco smoke in childhood and incidence of cancer in adulthood in never smokers in the European prospective investigation into cancer and nutrition. Cancer Causes Control 2011. 22(3):487-94. 
  13. Iodice S, Gandini S, Maisonneuve P, Lowenfels AB.  Tobacco and the risk of pancreatic cancer: a review and meta-analysis. Langenbecks Arch Surg 2008. 
  14. Cogliano VJ, Baan R, Straif K et al.  Preventable exposures associated with human cancers.JNCI 2011. 103(24):1827-39. 
  15. Luo J, Ye W, Zendehdel K, et al.  Oral use of Swedish moist snuff (snus) and risk for cancer of the mouth, lung, and pancreas in male construction workers: a retrospective cohort study.Lancet 2007;369(9578):2015-20. 
  16. Michaud,D.S., et al.,  Alcohol intake and pancreatic cancer: a pooled analysis from the pancreatic cancer cohort consortium (PanScan). Cancer Causes Control 2010 
  17. WCRF/AICR (World Cancer Research Fund/American Institute for Cancer Research) (2007) Food, nutrition, physical activity and the prevention of cancer: a global perspective 
  18. Parkin et al., (2011) The fraction of cancer attributable to lifestyle and environmental factors in the UK in 2010. British Journal of Cancer 105, S77 – S81 
  19. Reeves G, Pirie K, Beral V, Green J, Spencer E, Bull D, for the Million Women Study collaborators (2007) Cancer incidence and mortality in relation to Body Mass Index in the Million Women Study: cohort study. British Medical Journal. Dec 1; 335 (7630): 1134 
  20. J. Lou et al., (2008) Obesity and the risk of pancreatic cancer among post-menopausal women: the Women’s Health Initiative (United States) British Journal of Cancer 99: 527-531 
  21. Aune, D., et al.,  Body mass index, abdominal fatness and pancreatic cancer risk: a systematic review and non-linear dose-response meta-analysis of prospective studies. Ann Oncol, 2011. 
  22. Chari et al., (2005) Probability of pancreatic cancer following diabetes: a population based study. Gastroenterology 129: 504-511 
  23. Huxley, R., et al.,  Type-II diabetes and pancreatic cancer: a meta-analysis of 36 studies. Br J Cancer, 2005. 92(11): p. 2076-83. 
  24. Stolzenberg-Solomon, R.Z., et al.,  Insulin, glucose, insulin resistance, and pancreatic cancer in male smokers. Jama, 2005. 294(22): p. 2872-8. 
  25. Stevens RJ, Roddam AW, Beral V.  Pancreatic cancer in type 1 and young-onset diabetes: systematic review and meta-analysis. BJC 2007;96(3):507-9. 
  26. Soranna D, Scotti L, Zambon A et al.  Cancer risk associated with use of metformin and sulfonylurea in type 2 diabetes: a meta-analysis. Oncologist. 2012;17(6):813-22. 
  27. Bodmer et al., (2012) Use of Antidiabetic Agents and the Risk of Pancreatic Cancer: A Case-Control Analysis. Am J Gastroenterol advance online publication 31 January 2012; doi: 10.1038/ajg.2011.483 
  28. Pannala, R et al., (2008) Prevalence and clinical profile of pancreatic cancer –associated diabetes mellitus. Gastroenterology 134 (4): 981-987 
  29. Chari et al., (2008) Pancreatic cancer-associated diabetes mellitus. Gastroenterology 134 (1): 95-101 pp 271-274. 
  30. Duell EJ, Lucenteforte E, Olson SH et al.  Pancreatitis and pancreatic cancer risk: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4). Ann Oncol. 2012. 

  31. Malka, D., et al.,  Risk of pancreatic adenocarcinoma in chronic pancreatitis. Gut, 2002. 51(6): p. 849-52. 
  32. Bansal, P. and A. Sonnenberg,  Pancreatitis is a risk factor for pancreatic     cancer.Gastroenterology, 1995. 109(1): p. 247-51. 
  33. Duell EJ, Lucenteforte E, Olson SH et al.  Pancreatitis and pancreatic cancer risk: a pooled analysis in the International Pancreatic Cancer Case-Control Consortium (PanC4). Ann Oncol. 2012. 
  34. Lowenfels, A.B., P. Maisonneuve, and D.C. Whitcomb,  Risk factors for cancer in hereditary pancreatitis. International Hereditary Pancreatitis Study Group. Med Clin North Am, 2000. 84(3): p. 565-73. 
  35. Rebours, V., et al.,  Risk of pancreatic adenocarcinoma in patients with hereditary pancreatitis: a national exhaustive series.Am J Gastroenterol, 2008. 103(1): p. 111-9. 
  36. Jacobs, E.J., et al.  Famly history of cancer and risk of pancreatic cancer: A pooled analysis from the pancreatic cancer cohort consortium (PANSCAN). Int J Cancer 2010. 
  37. Shen, M., et al.,  A pooled analysis of second primary pancreatic cancer. Am J Epidemiol 2006; 163(6):502-11. 
  38. Hemminki, K., et al.,  Cancer risks in Crohn disease patients. Ann Oncol 2009; 20(3):574-80. 
  39. Luo J, Nordenvall C, Nyren O, Adami HO, Permert J, and Ye W. The risk of pancreatic cancer in patients with gastric or duodenal ulcer disease. Int J Cancer 2007; 120: 368-72 
  40. Michaud, D.S., et al.,  Periodontal disease, tooth loss, and cancer risk in male health professionals: a prospective cohort study. Lancet Oncol 2008; 9(6):550-8. 
  41. Arora, M., et al.,  An exploration of shared genetic risk factors between periodontal disease and cancers: a prospective co-twin study. Am J Epidemiol 2010; 171(2):253-9. 

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Information Product No. PCA0032 | Published: 20/10/2012 | Last Updated: 27/02/2013 | Next Review Due: 27/02/2016