Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Epidemiology of pancreatic cancer: an overview

Abstract

Pancreatic cancer, although infrequent, has an exceptionally high mortality rate, making it one of the four or five most common causes of cancer mortality in developed countries. The incidence of pancreatic cancer varies greatly across regions, which suggests roles for lifestyle factors, such as diet, or environmental factors, such as vitamin D exposure. Smoking is the most common known risk factor, and is the cause of 20–25% of all pancreatic tumors. Alcohol does not seem to be a risk factor, unless it leads to chronic pancreatitis, which is a probable risk factor. Long-standing diabetes increases the risk of pancreatic cancer, but can also be an early manifestation of pancreatic tumors. 5–10% of patients with pancreatic cancer have an underlying germline disorder, while the remaining percentage of cancer cases is thought to be caused by somatic mutations. Some individual studies suggest that mutations in various polymorphic genes can lead to small increases in the risk of pancreatic cancer, but these findings need to be replicated. Rising prevalence of smoking in developing countries, improved diagnosis and increasing population longevity are all likely to increase the global burden of pancreatic cancer in the coming decades.

Key Points

  • Despite its low incidence in developed countries, pancreatic cancer is associated with poor survival and ranks as the fourth or fifth most common cause of cancer mortality

  • Smoking causes 20–25% of pancreatic cancer cases and is the most frequent cause of this tumor, yet it is the most preventable

  • Chronic pancreatitis and diabetes are two benign diseases that have been linked to pancreatic cancer

  • 5–10% of patients with pancreatic cancer have an underlying germline disorder, while the remaining cases seem to result from damage to genes occurred during life

  • Some apparently sporadic pancreatic cancers may in fact be caused by the interaction of polymorphic genes with other genes or with environmental factors

  • Potentially important risk factors that need further study include Helicobacter pylori and viral infections, and drugs such as aspirin, NSAIDS, and statins

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1: Global age-standardized incidence rates of pancreatic cancer in men, based on data from 235 global cancer registries in 40 countries.

References

  1. Parkin, D. M., Bray, F., Ferlay, J. & Pisani, P. Estimating the world cancer burden: Globocan 2000. Int. J. Cancer 94, 153–156 (2001).

    Article  CAS  PubMed  Google Scholar 

  2. Carpelan-Holmstrom, M. et al. Does anyone survive pancreatic ductal adenocarcinoma? A nationwide study re-evaluating the data of the Finnish Cancer Registry. Gut 54, 385–387 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Curado, M. P. et al. (eds) Cancer Incidence in Five Continents Vol. 9 (IARC Scientific Publications No. 160, Lyon, 2007).

    Google Scholar 

  4. Kinoshita, S., Wagatsuma, Y. & Okada, M. Geographical distribution for malignant neoplasm of the pancreas in relation to selected climatic factors in Japan. Int. J. Health Geogr. 6, 34 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  5. Giovannucci, E. et al. Prospective study of predictors of vitamin D status and cancer incidence and mortality in men. J. Natl Cancer Inst. 98, 451–459 (2006).

    Article  CAS  PubMed  Google Scholar 

  6. Grant, W. B. & Mohr, S. B. Ecological studies of ultraviolet B, vitamin D and cancer since 2000. Ann. Epidemiol. 19, 446–454 (2009).

    Article  PubMed  Google Scholar 

  7. Parkin, D. M., Bray, F., Ferlay, J. & Pisani, P. Global cancer statistics, 2002. CA Cancer J. Clin. 55, 74–108 (2005).

    Article  PubMed  Google Scholar 

  8. Raimondi, S., Maisonneuve, P., Lohr, J. M. & Lowenfels, A. B. Early onset pancreatic cancer: evidence of a major role for smoking and genetic factors. Cancer Epidemiol. Biomarkers Prev. 16, 1894–1897 (2007).

    Article  PubMed  Google Scholar 

  9. Deutsch, M., Rosenstein, M. M. & Ramanathan, R. K. Pancreatic cancer in a young adult after treatment for Hodgkin's disease. Clin. Oncol. (R. Coll. Radiol.) 11, 280–282 (1999).

    Article  CAS  Google Scholar 

  10. Wahi, M. M., Shah, N., Schrock, C. E., Rosemurgy, A. S. & Goldin, S. B. Reproductive factors and risk of pancreatic cancer in women: a review of the literature. Ann. Epidemiol. 19, 103–111 (2009).

    Article  PubMed  Google Scholar 

  11. Horner, M. J. et al. (Eds) SEER Cancer Statistics Review, 1975–2006, National Cancer Institute [online], (2009).

    Google Scholar 

  12. Silverman, D. T. et al. Why do Black Americans have a higher risk of pancreatic cancer than White Americans? Epidemiology 14, 45–54 (2003).

    Article  PubMed  Google Scholar 

  13. Ginde, A. A., Liu, M. C. & Camargo, C. A. J. Demographic differences and trends of vitamin D insufficiency in the US population, 1988–2004. Arch. Intern. Med. 169, 626–632 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Muscat, J. E., Djordjevic, M. V., Colosimo, S., Stellman S. D. & Richie, J. P. J. Racial differences in exposure and glucuronidation of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Cancer 103, 1420–1426 (2005).

    Article  CAS  PubMed  Google Scholar 

  15. Lichtenstein, P. et al. Environmental and heritable factors in the causation of cancer--analyses of cohorts of twins from Sweden, Denmark, and Finland. N. Engl. J. Med. 343, 78–85 (2000).

    Article  CAS  PubMed  Google Scholar 

  16. Jiao, L. et al. A combined healthy lifestyle score and risk of pancreatic cancer in a large cohort study. Arch. Intern. Med. 169, 764–770 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  17. Iodice, S., Gandini, S., Maisonneuve, P. & Lowenfels, A. B. Tobacco and the risk of pancreatic cancer: a review and meta-analysis. Langenbecks Arch. Surg. 393, 535–545 (2008).

    Article  PubMed  Google Scholar 

  18. Boffetta, P., Hecht, S., Gray, N., Gupta, P. & Straif, K. Smokeless tobacco and cancer. Lancet Oncol. 9, 667–675 (2008).

    Article  PubMed  Google Scholar 

  19. Rohrmann, S. et al. Ethanol intake and the risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC). Cancer Causes Control 20, 785–794 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  20. Jiao, L. et al. Alcohol use and risk of pancreatic cancer: the NIH-AARP Diet and Health Study. Am. J. Epidemiol. 169, 1043–1051 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  21. Genkinger, J. M. et al. Alcohol intake and pancreatic cancer risk: a pooled analysis of fourteen cohort studies. Cancer Epidemiol. Biomarkers Prev. 18, 765–776 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Vrieling, A. et al. Fruit and vegetable consumption and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition. Int. J. Cancer 124, 1926–1934 (2009).

    Article  CAS  PubMed  Google Scholar 

  23. Nothlings, U., Murphy, S. P., Wilkens, L. R., Henderson, B. E. & Kolonel, L. N. Flavonols and pancreatic cancer risk: the multiethnic cohort study. Am. J. Epidemiol. 166, 924–931 (2007).

    Article  PubMed  Google Scholar 

  24. Stolzenberg-Solomon, R. Z. et al. Dietary and other methyl-group availability factors and pancreatic cancer risk in a cohort of male smokers. Am. J. Epidemiol. 153, 680–687 (2001).

    Article  CAS  PubMed  Google Scholar 

  25. Larsson, S. C., Hakansson, N., Giovannucci, E. & Wolk, A. Folate intake and pancreatic cancer incidence: a prospective study of Swedish women and men. J. Natl Cancer Inst. 98, 407–413 (2006).

    Article  CAS  PubMed  Google Scholar 

  26. Giovannucci, E. Vitamin D and cancer incidence in the Harvard cohorts. Ann. Epidemiol. 19, 84–88 (2009).

    Article  PubMed  Google Scholar 

  27. Gong, Z., Holly, E. A. & Bracci, P. M. Intake of folate, vitamins B(6), B (12) and methionine and risk of pancreatic cancer in a large population-based case-control study. Cancer Causes Control doi: 10.1007/s10552-009-9352–9359

  28. Larsson, S. C., Giovannucci, E. & Wolk, A. Methionine and vitamin B6 intake and risk of pancreatic cancer: a prospective study of Swedish women and men. Gastroenterology 132, 113–118 (2007).

    Article  CAS  PubMed  Google Scholar 

  29. Reeves, G. K. et al. Cancer incidence and mortality in relation to body mass index in the Million Women Study: cohort study. BMJ 335, 1134 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  30. Fryzek, J. P., Schenk, M., Kinnard, M., Greenson, J. K. & Garabrant, D. H. The association of body mass index and pancreatic cancer in residents of southeastern Michigan, 1996–1999. Am. J. Epidemiol. 162, 222–228 (2005).

    Article  PubMed  Google Scholar 

  31. Patel, A. V. et al. Obesity, recreational physical activity, and risk of pancreatic cancer in a large, U. S. Cohort. Cancer Epidemiol. Biomarkers Prev. 14, 459–466 (2005).

    Article  PubMed  Google Scholar 

  32. Berrington de González, A., Sweetland, S. & Spencer, E. A meta-analysis of obesity and the risk of pancreatic cancer. Br. J. Cancer 89, 519–523 (2003).

    Article  PubMed  Google Scholar 

  33. Khasawneh, J. et al. Inflammation and mitochondrial fatty acid beta-oxidation link obesity to early tumor promotion. Proc. Natl Acad. Sci. USA 106, 3354–3359 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Jiao, L. et al. Glycemic index, carbohydrates, glycemic load, and the risk of pancreatic cancer in a prospective cohort study. Cancer Epidemiol. Biomarkers Prev. 18, 1144–1151 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Bao, Y. et al. Added sugar and sugar-sweetened foods and beverages and the risk of pancreatic cancer in the National Institutes of Health-AARP Diet and Health Study. Am. J. Clin. Nutr. 88, 431–440 (2008).

    Article  CAS  PubMed  Google Scholar 

  36. Heinen, M. M. et al. Glycemic load, glycemic index, and pancreatic cancer risk in the Netherlands Cohort Study. Am. J. Clin. Nutr. 87, 970–977 (2008).

    Article  CAS  PubMed  Google Scholar 

  37. Gnagnarella, P., Gandini, S., La Vecchia, C. & Maisonneuve, P. Glycemic index, glycemic load, and cancer risk: a meta-analysis. Am. J. Clin. Nutr. 87, 1793–1801 (2008).

    Article  CAS  PubMed  Google Scholar 

  38. Larsson, S. C., Orsini, N. & Wolk, A. Body mass index and pancreatic cancer risk: A meta-analysis of prospective studies. Int. J. Cancer 120, 1993–1998 (2007).

    Article  CAS  PubMed  Google Scholar 

  39. Renehan, A. G., Tyson, M., Egger, M., Heller, R. F. & Zwahlen, M. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 371, 569–578 (2008).

    Article  PubMed  Google Scholar 

  40. Li, D. et al. Body mass index and risk, age of onset, and survival in patients with pancreatic cancer. JAMA 301, 2553–1562 (2209).

    Article  Google Scholar 

  41. Berrington de González, A. et al. Anthropometry, physical activity, and the risk of pancreatic cancer in the European prospective investigation into cancer and nutrition. Cancer Epidemiol. Biomarkers Prev. 15, 879–885 (2006).

    Article  PubMed  Google Scholar 

  42. Stolzenberg-Solomon, R. Z. et al. Adiposity, physical activity, and pancreatic cancer in the National Institutes of Health-AARP Diet and Health Cohort. Am. J. Epidemiol. 167, 586–597 (2008).

    Article  PubMed  Google Scholar 

  43. Calton, B. A. et al. A prospective study of physical activity and the risk of pancreatic cancer among women (United States). BMC Cancer 8, 63 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  44. Stevens, R. J. et al. Factors associated with incident and fatal pancreatic cancer in a cohort of middle-aged women. Int. J. Cancer 124, 2400–2405 (2009).

    Article  CAS  PubMed  Google Scholar 

  45. Anderson, K. E., Johnson, T. W., Lazovich, D. & Folsom, A. R. Association between nonsteroidal anti-inflammatory drug use and the incidence of pancreatic cancer. J. Natl Cancer Inst. 94, 1168–1171 (2002).

    Article  PubMed  Google Scholar 

  46. Capurso, G. et al. Meta-analysis: the use of non-steroidal anti-inflammatory drugs and pancreatic cancer risk for different exposure categories. Aliment. Pharmacol. Ther. 26, 1089–1099 (2007).

    Article  CAS  PubMed  Google Scholar 

  47. Coogan, P. F. et al. Nonsteroidal anti-inflammatory drugs and risk of digestive cancers at sites other than the large bowel. Cancer Epidemiol. Biomarkers Prev. 9, 119–123 (2000).

    CAS  PubMed  Google Scholar 

  48. Jacobs, E. J. et al. Aspirin use and pancreatic cancer mortality in a large United States cohort. J. Natl Cancer Inst. 96, 524–528 (2004).

    Article  CAS  PubMed  Google Scholar 

  49. Larsson, S. C., Giovannucci, E., Bergkvist, L. & Wolk, A. Aspirin and nonsteroidal anti-inflammatory drug use and risk of pancreatic cancer: a meta-analysis. Cancer Epidemiol. Biomarkers Prev. 15, 2561–2564 (2006).

    Article  CAS  PubMed  Google Scholar 

  50. Menezes, R. J., Huber, K. R., Mahoney, M. C. & Moysich, K. B. Regular use of aspirin and pancreatic cancer risk. BMC Public Health 2, 18 (2002).

    Article  PubMed  PubMed Central  Google Scholar 

  51. Schernhammer, E. S. et al. A prospective study of aspirin use and the risk of pancreatic cancer in women. J. Natl Cancer Inst. 96, 22–28 (2004).

    Article  CAS  PubMed  Google Scholar 

  52. Sumi, S. et al. Inhibition of pancreatic adenocarcinoma cell growth by lovastatin. Gastroenterology 103, 982–989 (1992).

    Article  CAS  PubMed  Google Scholar 

  53. Bonovas, S., Filioussi, K. & Sitaras, N. M. Statins are not associated with a reduced risk of pancreatic cancer at the population level, when taken at low doses for managing hypercholesterolemia: evidence from a meta-analysis of 12 studies. Am. J. Gastroenterol. 103, 2646–2651 (2008).

    Article  CAS  PubMed  Google Scholar 

  54. Luo, J. et al. Body mass index, physical activity and the risk of pancreatic cancer in relation to smoking status and history of diabetes: a large-scale population-based cohort study in Japan—the JPHC study. Cancer Causes Control 18, 603–612 (2007).

    Article  PubMed  Google Scholar 

  55. Hassan, M. M. et al. Risk factors for pancreatic cancer: case-control study. Am. J. Gastroenterol. 102, 2696–2707 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  56. Huxley, R., Ansary-Moghaddam, A., Berrington de González, A., Barzi, F. & Woodward, M. Type-II diabetes and pancreatic cancer: a meta-analysis of 36 studies. Br. J. Cancer 92, 2076–2083 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Chari, S. T. et al. Pancreatic cancer-associated diabetes mellitus: prevalence and temporal association with diagnosis of cancer. Gastroenterology 134, 95–101 (2008).

    Article  CAS  PubMed  Google Scholar 

  58. Li, D., Yeung, S. C., Hassan, M. M., Konopleva, M. & Abbruzzese, J. L. Antidiabetic therapies affect risk of pancreatic cancer. Gastroenterology 137, 482–488 (2009).

    Article  PubMed  Google Scholar 

  59. Lowenfels, A. B. et al. Pancreatitis and the risk of pancreatic cancer. International Pancreatitis Study Group. N. Engl. J. Med. 328, 1433–1437 (1993).

    Article  CAS  PubMed  Google Scholar 

  60. Malka, D. et al. Risk of pancreatic adenocarcinoma in chronic pancreatitis. Gut 51, 849–852 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Hart, A. R., Kennedy, H. & Harvey, I. Pancreatic cancer: a review of the evidence on causation. Clin. Gastroenterol. Hepatol. 6, 275–282 (2008).

    Article  PubMed  Google Scholar 

  62. Lowenfels, A. B. et al. Hereditary pancreatitis and the risk of pancreatic cancer. International Hereditary Pancreatitis Study Group. J. Natl Cancer Inst. 89, 442–446 (1997).

    Article  CAS  PubMed  Google Scholar 

  63. Howes, N. et al. Clinical and genetic characteristics of hereditary pancreatitis in Europe. Clin. Gastroenterol. Hepatol. 2, 252–261 (2004).

    Article  CAS  PubMed  Google Scholar 

  64. Rebours, V. et al. Risk of pancreatic adenocarcinoma in patients with hereditary pancreatitis: a national exhaustive series. Am. J. Gastroenterol. 103, 111–119 (2008).

    Article  PubMed  Google Scholar 

  65. Anderson, L. N., Cotterchio, M. & Gallinger, S. Lifestyle, dietary, and medical history factors associated with pancreatic cancer risk in Ontario, Canada. Cancer Causes Control doi: 10.1007/s10552-009-9303–9305

  66. Gandini, S., Lowenfels, A. B., Jaffee, E. M., Armstrong, T. D. & Maisonneuve, P. Allergies and the risk of pancreatic cancer: a meta-analysis with review of epidemiology and biological mechanisms. Cancer Epidemiol. Biomarkers Prev. 14, 1908–1916 (2005).

    Article  PubMed  Google Scholar 

  67. Olson, S. H. et al. Allergies, variants in IL-4 and IL-4R alpha genes, and risk of pancreatic cancer. Cancer Detect. Prev. 31, 345–351 (2007).

    Article  CAS  PubMed  Google Scholar 

  68. Turner, M. C., Chen, Y., Krewski, D. & Ghadirian, P. An overview of the association between allergy and cancer. Int. J. Cancer 118, 3124–3132 (2006).

    Article  CAS  PubMed  Google Scholar 

  69. Sherman, P. W., Holland, E. & Sherman, J. S. Allergies: their role in cancer prevention. Q. Rev. Biol. 83, 339–362 (2008).

    Article  PubMed  Google Scholar 

  70. Farrow, D. C. & Davis, S. Risk of pancreatic cancer in relation to medical history and the use of tobacco, alcohol and coffee. Int. J. Cancer 45, 816–820 (1990).

    Article  CAS  PubMed  Google Scholar 

  71. Stolzenberg-Solomon, R. Z., Pietinen, P., Taylor, P. R., Virtamo, J. & Albanes, D. A. prospective study of medical conditions, anthropometry, physical activity, and pancreatic cancer in male smokers (Finland). Cancer Causes Control 13, 417–426 (2002).

    Article  PubMed  Google Scholar 

  72. Meyer, M. S., Joshipura, K., Giovannucci, E. & Michaud, D. S. A review of the relationship between tooth loss, periodontal disease, and cancer. Cancer Causes Control 19, 895–907 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  73. El-Serag, H. B. et al. Risk of hepatobiliary and pancreatic cancers after hepatitis C virus infection: A population-based study of U. S. veterans. Hepatology 49, 116–123 (2009).

    Article  PubMed  Google Scholar 

  74. Hassan, M. M. et al. Association between hepatitis B virus and pancreatic cancer. J. Clin. Oncol. 26, 4557–4562 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  75. Raderer, M. et al. Association between Helicobacter pylori infection and pancreatic cancer. Oncology 55, 16–19 (1998).

    Article  CAS  PubMed  Google Scholar 

  76. Stolzenberg-Solomon, R. Z. et al. Helicobacter pylori seropositivity as a risk factor for pancreatic cancer. J. Natl Cancer Inst. 93, 937–941 (2001).

    Article  CAS  PubMed  Google Scholar 

  77. Lindkvist, B., Johansen, D., Borgstrom, A. & Manjer, J. A prospective study of Helicobacter pylori in relation to the risk for pancreatic cancer. BMC Cancer 8, 321 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  78. Wolpin, B. M. et al. ABO blood group and the risk of pancreatic cancer. J. Natl Cancer Inst. 101, 424–431 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Landi, S. Genetic predisposition and environmental risk factors to pancreatic cancer: A review of the literature. Mutat. Res. 681, 299–307 (2009).

    Article  CAS  PubMed  Google Scholar 

  80. Goldstein, A. M., Struewing, J. P., Fraser, M. C., Smith, M. W. & Tucker, M. A. Prospective risk of cancer in CDKN2A germline mutation carriers. J. Med. Genet. 41, 421–424 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Vasen, H. F. et al. Risk of developing pancreatic cancer in families with familial atypical multiple mole melanoma associated with a specific 19 deletion of p16 (p16-Leiden). Int. J. Cancer 87, 809–811 (2000).

    Article  CAS  PubMed  Google Scholar 

  82. De Snoo, F. A. et al. Increased risk of cancer other than melanoma in CDKN2A founder mutation (p16-Leiden)-positive melanoma families. Clin. Cancer Res. 14, 7151–7157 (2008).

    Article  CAS  PubMed  Google Scholar 

  83. Goldstein, A. M. et al. High-risk melanoma susceptibility genes and pancreatic cancer, neural system tumors, and uveal melanoma across GenoMEL. Cancer Res. 66, 9818–9828 (2006).

    Article  CAS  PubMed  Google Scholar 

  84. Howes, N. et al. Clinical and genetic characteristics of hereditary pancreatitis in Europe. Clin. Gastroenterol. Hepatol. 2, 252–261 (2004).

    Article  CAS  PubMed  Google Scholar 

  85. Lowenfels, A. B., Maisonneuve, P., Whitcomb, D. C., Lerch, M. M. & DiMagno, E. P. Cigarette smoking as a risk factor for pancreatic cancer in patients with hereditary pancreatitis. JAMA 286, 169–170 (2001).

    Article  CAS  PubMed  Google Scholar 

  86. Giardiello, F. M. et al. Very high risk of cancer in familial Peutz–Jeghers syndrome. Gastroenterology 119, 1447–1453 (2000).

    Article  CAS  PubMed  Google Scholar 

  87. Hearle, N. et al. Frequency and spectrum of cancers in the Peutz–Jeghers syndrome. Clin. Cancer Res. 12, 3209–3215 (2006).

    Article  CAS  PubMed  Google Scholar 

  88. Lim, W. et al. Relative frequency and morphology of cancers in STK11 mutation carriers. Gastroenterology 126, 1788–1794 (2004).

    Article  CAS  PubMed  Google Scholar 

  89. Pogue-Geile, K. L. et al. Palladin mutation causes familial pancreatic cancer and suggests a new cancer mechanism. PLoS Med. 3, e516 (2006).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  90. Klein, A. P. et al. Absence of deleterious palladin mutations in patients with familial pancreatic cancer. Cancer Epidemiol. Biomarkers Prev. 18, 1328–1330 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. McWilliams, R. et al. Cystic fibrosis transmembrane regulator gene carrier status is a risk factor for young onset pancreatic adenocarcinoma. Gut 54, 1661–1662 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Maisonneuve, P., Marshall, B. C. & Lowenfels, A. B. Risk of pancreatic cancer in patients with cystic fibrosis. Gut 56, 1327–1328 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Malats, N. et al. Cystic fibrosis transmembrane regulator (CFTR) DeltaF508 mutation and 5T allele in patients with chronic pancreatitis and exocrine pancreatic cancer. PANKRAS II Study Group. Gut 48, 70–74 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Hahn, S. A. et al. BRCA2 germline mutations in familial pancreatic carcinoma. J. Natl Cancer Inst. 95, 214–221 (2003).

    Article  CAS  PubMed  Google Scholar 

  95. van Asperen, C. J. et al. Cancer risks in BRCA2 families: estimates for sites other than breast and ovary. J. Med. Genet. 42, 711–719 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Risch, H. A. et al. Population BRCA1 and BRCA2 mutation frequencies and cancer penetrances: a kin-cohort study in Ontario, Canada. J. Natl Cancer Inst. 98, 1694–1706 (2006).

    Article  CAS  PubMed  Google Scholar 

  97. Couch, F. J. et al. The prevalence of BRCA2 mutations in familial pancreatic cancer. Cancer Epidemiol. Biomarkers Prev. 16, 342–346 (2007).

    Article  CAS  PubMed  Google Scholar 

  98. Ferrone, C. R. et al. BRCA germline mutations in Jewish patients with pancreatic adenocarcinoma. J. Clin. Oncol. 27, 433–438 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Cho, J. H., Bang, S., Park, S. W., Chung, J. B. & Song, S. Y. BRCA2 mutations as a universal risk factor for pancreatic cancer has a limited role in Korean ethnic group. Pancreas 36, 337–340 (2008).

    Article  CAS  PubMed  Google Scholar 

  100. Real, F. X. et al. Family history of cancer and germline BRCA2 mutations in sporadic exocrine pancreatic cancer. Gut 50, 653–657 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Jones, S. et al. Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene. Science 324, 217 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Giardiello, F. M. et al. Increased risk of thyroid and pancreatic carcinoma in familial adenomatous polyposis. Gut 34, 1394–1396 (1993).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Kleihues, P., Schauble, B., zur Hausen, A., Esteve, J. & Ohgaki, H. Tumors associated with p53 germline mutations: a synopsis of 91 families. Am. J. Pathol. 150, 1–13 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Geary, J. et al. Gene-related cancer spectrum in families with hereditary non-polyposis colorectal cancer (HNPCC). Fam. Cancer 7, 163–172 (2008).

    Article  CAS  PubMed  Google Scholar 

  105. Maitra, A. & Hruban, R. H. Pancreatic cancer. Annu. Rev. Pathol. 3, 157–188 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Su, G. H. et al. Germline and somatic mutations of the STK11/LKB1 Peutz–Jeghers gene in pancreatic and biliary cancers. Am. J. Pathol. 154, 1835–1840 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Blackford, A. et al. Genetic mutations associated with cigarette smoking in pancreatic cancer. Cancer Res. 69, 3681–3688 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Crous-Bou, M. et al. Lifetime history of alcohol consumption and K-ras mutations in pancreatic ductal adenocarcinoma. Environ. Mol. Mutagen. 50, 421–430 (2009).

    Article  CAS  PubMed  Google Scholar 

  109. Morales, E. et al. Food and nutrient intakes and K-ras mutations in exocrine pancreatic cancer. J. Epidemiol. Community Health 61, 641–649 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  110. Jiao, L. et al. Glutathione S-transferase gene polymorphisms and risk and survival of pancreatic cancer. Cancer 109, 840–848 (2007).

    Article  CAS  PubMed  Google Scholar 

  111. Li, D. et al. Polymorphisms of cytochrome P4501A2 and N-acetyltransferase genes, smoking, and risk of pancreatic cancer. Carcinogenesis 27, 103–111 (2006).

    Article  PubMed  CAS  Google Scholar 

  112. Ayaz, L., Ercan, B., Dirlik, M., Atik, U. & Tamer, L. The association between N-acetyltransferase 2 gene polymorphisms and pancreatic cancer. Cell. Biochem. Funct. 26, 329–333 (2008).

    Article  CAS  PubMed  Google Scholar 

  113. Ockenga, J., Vogel, A., Teich, N., Keim, V., Manns, M. P. & Strassburg, C. P. UDP glucuronosyltransferase (UGT1A7) gene polymorphisms increase the risk of chronic pancreatitis and pancreatic cancer. Gastroenterology 124, 1802–1808 (2003).

    Article  CAS  PubMed  Google Scholar 

  114. Suzuki, H. et al. Interaction of the cytochrome P4501A2, SULT1A1 and NAT gene polymorphisms with smoking and dietary mutagen intake in modification of the risk of pancreatic cancer. Carcinogenesis 29, 1184–1191 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Duell, E. J. et al. A population-based, case-control study of polymorphisms in carcinogen-metabolizing genes, smoking, and pancreatic adenocarcinoma risk. J. Natl Cancer Inst. 94, 297–306 (2002).

    Article  CAS  PubMed  Google Scholar 

  116. Li, D. et al. 5, 10-Methylenetetrahydrofolate reductase polymorphisms and the risk of pancreatic cancer. Cancer Epidemiol. Biomarkers Prev. 14, 1470–1476 (2005).

    Article  CAS  PubMed  Google Scholar 

  117. Wang, L. et al. Genetic polymorphisms in methylenetetrahydrofolate reductase and thymidylate synthase and risk of pancreatic cancer. Clin. Gastroenterol. Hepatol. 3, 743–751 (2005).

    Article  CAS  PubMed  Google Scholar 

  118. Nisevic, I. et al. MTHFR C677T polymorphism in chronic pancreatitis and pancreatic adenocarcinoma. Cell. Biochem. Funct. 26, 659–663 (2008).

    Article  CAS  PubMed  Google Scholar 

  119. Suzuki, T. et al. Alcohol drinking and one-carbon metabolism-related gene polymorphisms on pancreatic cancer risk. Cancer Epidemiol. Biomarkers Prev. 17, 2742–2747 (2008).

    Article  CAS  PubMed  Google Scholar 

  120. Li, D. et al. DNA repair gene polymorphisms and risk of pancreatic cancer. Clin. Cancer Res. 15, 740–746 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. McWilliams, R. R. et al. Polymorphisms in DNA repair genes, smoking, and pancreatic adenocarcinoma risk. Cancer Res. 68, 4928–4935 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Duell, E. J. et al. Detecting pathway-based gene-gene and gene–environment interactions in pancreatic cancer. Cancer Epidemiol. Biomarkers Prev. 17, 1470–1479 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Jiao, L. et al. XRCC2 and XRCC3 gene polymorphism and risk of pancreatic cancer. Am. J. Gastroenterol. 103, 360–367 (2008).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors were supported by grants from the C. D. Smithers Foundation and Solvay Pharmaceuticals.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sara Raimondi.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Raimondi, S., Maisonneuve, P. & Lowenfels, A. Epidemiology of pancreatic cancer: an overview. Nat Rev Gastroenterol Hepatol 6, 699–708 (2009). https://doi.org/10.1038/nrgastro.2009.177

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrgastro.2009.177

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing