Epidemiology, Risk Factors and Clinical Presentation

  • Gabriele Capurso
  • Cesare Hassan
  • Gianfranco Delle Fave
  • Emilio Di Giulio
Part of the Medical Radiology book series (MEDRAD)


Pancreatic cancer (PDAC) is a deadly disease. It has an incidence ranging 8–12 per 100,000 per year, with a similar mortality, as more than 95% of patients diagnosed with PDAC will ultimately die. Prevention policies are therefore particularly important and they should be distinguished in: (1) Primary prevention, aimed at reducing risk factors for PDAC and possibly favouring protective habits. (2) Secondary prevention, aimed at the early diagnosis through appropriate screening tests in subjects with a particularly high risk. The most important risk factors for pancreatic cancer are family history of pancreatic cancer, smoking, obesity, diabetes, alcohol and chronic pancreatitis. Diabetes of recent onset should be considered a possible alarm symptom. In patients with defined genetic syndromes such as “familiar pancreatic cancer”, and Peutz–Jeghers syndrome screening for pancreatic cancer as a part of research protocols are performed in selected Centres. There are no sufficient data to suggest that vitamins or aspirin may have a role for PDAC chemoprevention.


Pancreatic Cancer Chronic Pancreatitis Cystic Fibrosis Transmembrane Conductance Regulator Familial Adenomatous Polyposis PDAC Patient 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Anderson KE, Sinha R, Kulldorff M, Gross M, Lang NP, Barber C, Harnack L, DiMagno E, Bliss R, Kadlubar FF (2002) Meat intake and cooking techniques: associations with pancreatic cancer. Mutat Res 506–507:225–231PubMedCrossRefGoogle Scholar
  2. Berrington de Gonzalez A, Sweetland S, Spencer E (2003) A meta-analysis of obesity and the risk of pancreatic caner. Br J Cancer 89:519–523PubMedCentralPubMedCrossRefGoogle Scholar
  3. Berrino F, De Angelis R, Sant M et al (2007) Survival for eight major cancers and all cancers combined for European adults diagnosed in 1995–99: results of the EUROCARE-4 study. Lancet Oncol 8:773–783PubMedCrossRefGoogle Scholar
  4. Bjelakovic G, Nikolova D, Simonetti RG, Gluud C (2004) Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-analysis. Lancet 364(9441):1219–1228PubMedCrossRefGoogle Scholar
  5. Bonovas S, Filioussi K, Sitaras NM (2008) 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(10):2646–2651PubMedCrossRefGoogle Scholar
  6. Borg A, Sandberg T, Nilsson K et al (2000) High frequency of multiple melanomas and breast and pancreas carcinomas in CDKN2A mutation-positive melanomafamilies. J Natl Cancer Inst 92:1260–1266PubMedCrossRefGoogle Scholar
  7. Brand RE, Lerch MM, Rubinstein WS, Neoptolemos JP, Whitcomb DC, Hruban RH, Brentnall TA, Lynch HT, Canto MI, Participants of the Fourth International Symposium of Inherited Diseases of the Pancreas (2007) Advances in counselling and surveillance of patients at risk for pancreatic cancer. Gut 56(10):1460–1469PubMedCentralPubMedCrossRefGoogle Scholar
  8. Brand RE, Greer JB, Zolotarevsky E, Brand R, Du H, Simeone D, Zisman A, Gorchow A, Lee SY, Roy HK, Anderson MA (2009) Pancreatic cancer patients who smoke and drink are diagnosed at younger ages. Clin Gastroenterol Hepatol 7:1007–1012PubMedCentralPubMedCrossRefGoogle Scholar
  9. Brentnall TA, Bronner MP, Byrd DR, Haggitt RC, Kimmey MB (1999) Early diagnosis and treatment of pancreatic dysplasia in patients with a family history of pancreatic cancer. Ann Intern Med 131(4):247–255PubMedCrossRefGoogle Scholar
  10. Canto MI, Goggins M, Hruban RH, Petersen GM, Giardiello FM, Yeo C, Fishman EK, Brune K, Axilbund J, Griffin C, Ali S, Richman J, Jagannath S, Kantsevoy SV, Kalloo AN (2006) Screening for early pancreatic neoplasia in high-risk individuals: a prospective controlled study. Clin Gastroenterol Hepatol 4(6):684–687CrossRefGoogle Scholar
  11. Capurso G, Delle Fave G, Lemoine N (2004) Re: etiology of pancreatic cancer, with a hypothesis concerning the role of N-nitroso compounds and excess gastric acidity. J Natl Cancer Inst 96:75PubMedCrossRefGoogle Scholar
  12. Capurso G, Schünemann HJ, Terrenato I, Moretti A, Koch M, Muti P, Capurso L, Delle Fave G (2007) Meta-analysis: the use of non-steroidal anti-inflammatory drugs and pancreatic cancer risk for different exposure categories. Aliment Pharmacol Ther 26(8):1089–1099PubMedCrossRefGoogle Scholar
  13. Couch FJ, Johnson MR, Rabe KG et al (2007) The prevalence of BRCA2 mutations in familial pancreatic cancer. Cancer Epidemiol Biomarkers Prev 16:342–346PubMedCrossRefGoogle Scholar
  14. Del Chiaro M, Zerbi A, Falconi M, Bertacca L, Polese M, Sartori N, Boggi U, Casari G, Longoni BM, Salvia R, Caligo MA, Di Carlo V, Pederzoli P, Presciuttini S, Mosca F (2007) Cancer risk among the relatives of patients with pancreatic ductal adenocarcinoma. Pancreatology 7(5–6):459–469PubMedGoogle Scholar
  15. de Martel C, Llosa AE, Friedmana GD, Vogelman JH, Orentreich N, Stolzenberg-Solomon RZ et al (2008) Helicobacter pylori infection and development of pancreatic cancer. Cancer Epidemiol Biomarkers Prev 17:1188–1194PubMedCrossRefGoogle Scholar
  16. Ferlay J, Autier P, Boniol M, Heanue M, Colombet M, Boyle P (2007) Estimates of the cancer incidence and mortality in Europe in 2006. Ann Oncol 18:581–592PubMedCrossRefGoogle Scholar
  17. Gandini S, Lowenfels AB, Jaffee EM, Armstrong TD, Maisonneuve P (2005) Allergies and the risk of pancreatic cancer: a meta-analysis with review of epidemiology and biological mechanisms. Cancer Epidemiol Biomarkers Prev 14(8):1908–1916PubMedCrossRefGoogle Scholar
  18. Garcea G, Dennison AR, Steward WP et al (2005) Role of inflammation in pancreatic carcinogenesis and the implications for future therapy. Pancreatology 5:514–529PubMedCrossRefGoogle Scholar
  19. Genkinger JM, Spiegelman D, Anderson KE, Bergkvist L, Bernstein L, van den Brandt PA, English DR, Freudenheim JL, Fuchs CS, Giles GG, Giovannucci E, Hankinson SE, Horn-Ross PL, Leitzmann M, Männistö S, Marshall JR, McCullough ML, Miller AB, Reding DJ, Robien K, Rohan TE, Schatzkin A, Stevens VL, Stolzenberg-Solomon RZ, Verhage BA, Wolk A, Ziegler RG, Smith-Warner SA (2009) Alcohol intake and pancreatic cancer risk: a pooled analysis of fourteen cohort studies. Cancer Epidemiol Biomarkers Prev 18(3):765–776PubMedCentralPubMedCrossRefGoogle Scholar
  20. Giardiello FM, Brensinger JD, Tersmette AC et al (2000) Very high risk of cancer in familial Peutz-Jeghers syndrome. Gastroenterology 119:1447–1453PubMedCrossRefGoogle Scholar
  21. Giovannucci E, Michaud D (2007) The role of obesity and related metabolic disturbances in cancers of the colon, prostate, and pancreas. Gastroenterology 132:2208–2225PubMedCrossRefGoogle Scholar
  22. Hassan MM, Bondy ML, Wolff RA, Abruzzese JL, Vauthey JN, Pisters PW et al (2007a) Risk factors for pancreatic cancer: case-control study. Am J Gastroenterol 102:1–12CrossRefGoogle Scholar
  23. Hassan MM, Abbruzzese JL, Bondy ML, Wolff RA, Vauthey JN, Pisters PW et al (2007b) Passive smoking and the use of noncigarette tobacco products in association with risk for pancreatic caner: a case-control study. Cancer 109:2547–2556PubMedCentralPubMedCrossRefGoogle Scholar
  24. Howes N, Lerch MM, Greenhalf W, Stocken DD, Ellis I, Simon P et al (2004) Clinical and genetic characteristics of hereditary pancreatitis in Europe. Clin Gastroenterol Hepatol 2: 252–261PubMedCrossRefGoogle Scholar
  25. Huxley R, Ansare-Moghaddam A, Berrington de Gonzalez A, Barzi F, Woodward M (2005) Type-II diabetes and pancreatic cancer: a meta-analysis of 36 studies. Brit J Cancer 92:2076–2083PubMedCentralPubMedCrossRefGoogle Scholar
  26. Iodice S, Gandini S, Maisonneuve P, Lowenfels AB (2008) Tobacco and the risk of pancreatic caner: a review and meta-analysis. Langebecks Arch Surg 393:535–545CrossRefGoogle Scholar
  27. Klein AP, Brune KA, Petersen GM, Goggins M, Tersmette AC, Offerhaus GJ, Griffin C, Cameron JL, Yeo CJ, Kern S, Hruban RH (2004) Prospective risk of pancreatic cancer in familial pancreatic cancer kindreds. Cancer Res. 64(7):2634–2638PubMedCrossRefGoogle Scholar
  28. Lal G, Liu G, Schmocker B et al (2000) Inherited predisposition to pancreatic adenocarcinoma: role of family history and germ-line p16, BRCA1 and BRCA2 mutations. Cancer Res 60:409–416PubMedGoogle Scholar
  29. Langer P, Kann PH, Fendrich V, Habbe N, Schneider M, Sina M, Slater EP, Heverhagen JT, Gress TM, Rothmund M, Bartsch DK (2009) 5 Years of prospective screening of high risk individuals from familial pancreatic cancer – families. Gut 58:1410–1418PubMedCrossRefGoogle Scholar
  30. Larsson SC, Giovannucci E, Wolk A (2006) Folate intake, MTHFR polymorphisms, and risk of esophageal, gastric, and pancreatic cancer: a meta-analysis. Gastroenterology 131(4): 271–1283PubMedCrossRefGoogle Scholar
  31. Larsson SC, Orsini N, Wolk A (2007) Body mass index and pancreatic cancer risk: a meta-analysis of prospective studies. Int J Cancer 120:1993–1998PubMedCrossRefGoogle Scholar
  32. Li D, Morris JS, Liu J, Hassan MM, Day RS, Bondy ML, Abbruzzese JL (2009a) Body mass index and risk, age of onset, and survival in patients with pancreatic cancer. JAMA 301(24):2553–2562PubMedCentralPubMedCrossRefGoogle Scholar
  33. Li D, Yeung SC, Hassan MM, Konopleva M, Abbruzzese JL (2009b) Antidiabetic therapies affect risk of pancreatic cancer. Gastroenterology 137:482–488PubMedCentralPubMedCrossRefGoogle Scholar
  34. Jiao L, Silverman DT, Schairer C, Thie’baut A, Hollenbeck AR, Leitzmann MF, Schatzkin A, Stolzenberg-Solomon RZ (2009a) Alcohol use and risk of pancreatic cancer. The NIH-AARP Diet and Health Study. Am J Epidemiol 169:1043–1051PubMedCentralPubMedCrossRefGoogle Scholar
  35. Lowenfels AB, Maisonneuve P, DiMagno EP et al (1997) Hereditary pancreatitis and the risk of pancreatic cancer. International Hereditary Pancreatitis Study Group. J Natl Cancer Inst 89:442–6PubMedCrossRefGoogle Scholar
  36. Lowenfels AB, Maisonneuve P, Whitcomb DC et al (2001) Cigarette smoking as a risk factor for pancreatic cancer in patients with hereditary pancreatitis. JAMA 286: 169–70PubMedCrossRefGoogle Scholar
  37. Lynch HT, Voorhees GJ, Lanspa SJ et al (1985) Pancreatic carcinoma and hereditary nonpolyposis colorectal cancer: a family study. Br J Cancer 52:271–3PubMedCentralPubMedCrossRefGoogle Scholar
  38. Luo J, Nordenvall C, Nyrén O, Adami HO, Permert J, Ye W (2007) The risk of pancreatic cancer in patients with gastric or duodenal ulcer disease. Int J Cancer 120:368–7PubMedCrossRefGoogle Scholar
  39. Jemal A, Seigel R, Ward E, Murray T, Xu J, Thun MJ (2007) Cancer statistics, 2007. CA Cancer J Clin 57:43–66PubMedCrossRefGoogle Scholar
  40. Jiao L, Mitrou PN, Reedy J, Graubard BI, Hollenbeck AR, Schatzkin A, Stolzenberg-Solomon R (2009b) A combined healthy lifestyle score and risk of pancreatic cancer in a large cohort study. Arch Intern Med 169:764–70PubMedCentralPubMedCrossRefGoogle Scholar
  41. Maisonneuve P, FitzSimmons SC, Neglia JP et al (2003) Cancer risk in nontransplanted and transplanted cystic fibrosis patients: a 10-year study. J Natl Cancer Inst 95:381–7PubMedCrossRefGoogle Scholar
  42. Maitra A, Ashfaq R, Gunn CR et al (2002) Cyclooxygenase 2 expression in pancreatic adenocarcinoma and pancreatic intraepithelial neoplasia: an immunohistochemical analysis with automated cellular imaging. Am J Clin Pathol 118:194–201PubMedCrossRefGoogle Scholar
  43. McKay CJ, Glen P, McMillan DC (2008) Chronic inflammation and pancreatic cancer. Best Pract Res Clin Gastroenterol 22:65–73PubMedCrossRefGoogle Scholar
  44. McWilliams R, Highsmith WE, Rabe KG, de Andrade M, Tordsen LA, Holtegaard LM, Petersen GM (2005) Cystic fibrosis transmembrane regulator gene carrier status is a risk factor for young onset pancreatic adenocarcinoma. Gut 54(11):1661–2PubMedCentralPubMedCrossRefGoogle Scholar
  45. McWilliams RR, Bamlet WR, Rabe KG, Olson JE, de Andrade M, Petersen GM (2006) Association of family history of specific cancers with a younger age of onset of pancreatic adenocarcinoma. Clin Gastroenterol Hepatol 4(9):1143–7PubMedCentralPubMedCrossRefGoogle Scholar
  46. Michaud DS, Giovannucci E, Willett WC, Colditz GA, Fuchs CS (2003) Dietary meat, dairy products, fat, and cholesterol and pancreatic cancer risk in a prospective study. Am J Epidemiol 157:1115–25PubMedCrossRefGoogle Scholar
  47. Mulder I, Hoogenveen RT, van Genugten ML (2002) Smoking cessation would substantially reduce the future incidence of pancreatic cancer in the European Union. Eur J Gastroenterol Hepatol 14:1343–53PubMedCrossRefGoogle Scholar
  48. Ojajärvi IA, Partanen TJ, Ahlbom A, Boffetta P, Hakulinen T, Jourenkova N et al (2000) Occupational exposures and pancreatic cancer: a meta-analysis. Occup Environ Med 57:316–24PubMedCentralPubMedCrossRefGoogle Scholar
  49. Pannala R, Leirness JB, Bamlet WR, Basu A, Petersen GM, Chari ST (2008) Prevalence and clinical profile of pancreatic cancer-associated diabetes mellitus. Gastroenterology 134:981–87PubMedCentralPubMedCrossRefGoogle Scholar
  50. Pannala R, Basu A, Petersen GM, Chari ST (2009) New-onset diabetes: a potential clue to the early diagnosis of pancreatic cancer. Lancet Oncol 10:88–95PubMedCentralPubMedCrossRefGoogle Scholar
  51. Pezzilli R, Morselli-Labate AM, Migliori M, Manca M, Bastagli L, Gullo L (2005) Obesity and the risk of pancreatic cancer: an italian multicenter study. Pancreas 31:221–224PubMedCrossRefGoogle Scholar
  52. Pogue-Geile KL, Chen R, Bronner MP, Crnogorac-Jurcevic T, Moyes KW, Dowen S, Otey CA, Crispin DA, George RD, Whitcomb DC, Brentnall TA (2006) Palladin mutation causes familial pancreatic cancer and suggests a new cancer mechanism. PLoS Med 3(12):e516PubMedCentralPubMedCrossRefGoogle Scholar
  53. Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M (2008) Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 371(9612):569–78PubMedCrossRefGoogle Scholar
  54. Rulyak SJ, Lowenfels AB, Maisonneuve P, Brentnall TA (2003) Risk factors for the development of pancreatic cancer in familial pancreatic cancer kindreds. Gastroenterology 124:1292–99PubMedCrossRefGoogle Scholar
  55. Schernhammer ES, Kang JH, Chan AT et al (2004) A prospective study of aspirin use and the risk of pancreatic cancer in women. J Natl Cancer Inst 96:22–8PubMedCrossRefGoogle Scholar
  56. Stevens RJ, Roddam AW, Beral V (2007) Pancreatic cancer in type 1 and young-onset diabetes: systematic review and meta-analysis. Br J Cancer 12(96):507–9CrossRefGoogle Scholar
  57. Stolzenberg-Solomon RZ, Blaser MJ, Limburg PJ, Perez-Perez G, Taylor PR, Virtamo J et al (2001) Helicobacter pylori seropositivity as a risk factor for pancreatic cancer. J Natl Cancer Inst 93:937–41PubMedCrossRefGoogle Scholar
  58. Talamini G, Falconi M, Bassi C, Sartori N, Salvia R, Caldiron E et al (1999) Incidence of cancer in the course of chronic pancreatitis. Am J Gastroenterol 92:1253–60CrossRefGoogle Scholar
  59. van Asperen CJ, Brohet RM, Meijers-Heijboer EJ et al (2005) Cancer risks in BRCA2 families: estimates for sites other than breast and ovary. J Med Genet 42:711–19PubMedCentralPubMedCrossRefGoogle Scholar
  60. Vasen HFA, Gruis NA, Frants RR et al (2000) Risk of developing pancreatic cancer in families with familial atypical multiple mole melanoma associated with a specific19 deletion of p16 (p16-LEIDEN). Int J Cancer 87:809–11PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2010

Authors and Affiliations

  • Gabriele Capurso
    • 1
  • Cesare Hassan
    • 2
  • Gianfranco Delle Fave
    • 1
  • Emilio Di Giulio
    • 1
  1. 1.Digestive and Liver Disease Unit, II Medical SchoolUniversity “La Sapienza”RomeItaly
  2. 2.Department of Gastroenterology“Nuovo Regina Margherita” HospitalRomeItaly

Personalised recommendations