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Pancreatic Cancer Epidemiology and Risk Factors Guenter J. Krejs

Pancreatic Cancer Epidemiology and Risk Factors Guenter J. Krejs Medical University of Graz, Austria. Pancreatic Cancer. 80% ductal pancreatic carcinoma 10% from exocrine tissue: acinar cell carcinoma cystadenocarcinoma giant-cell carcinoma intraductal papillar mucinous neoplasm

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Pancreatic Cancer Epidemiology and Risk Factors Guenter J. Krejs

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  1. Pancreatic Cancer Epidemiology and Risk Factors Guenter J. Krejs Medical University of Graz, Austria

  2. Pancreatic Cancer • 80% ductal pancreatic carcinoma • 10% from exocrine tissue: acinar cell carcinoma cystadenocarcinoma giant-cell carcinoma intraductal papillar mucinous neoplasm • 10% neuroendocrine tumors

  3. Pancreatic Cancer Average incidence: 10 per 100 000 pop. per year Cases per year: USA: 35 000 Germany 8 000 Austria 1 200 Average age at diagnosis 63 years

  4. Cancer of the pancreas in males, age-standardized incidence rate per 100 000 population for the year 2002

  5. Pancreatic Cancer Incidence and mortality are practically identical 250 000 deaths per year worldwide Ranks 8th in a worldwide listing of cancer mortality

  6. Pancreatic Cancer RISK FACTORS: Smoking High-fat diet, obesity, diabetes Chronic pancreatitis Hereditary pancreatitis Primary sclerosing cholangitis

  7. Vincent van Gogh

  8. Smoking and Cancer

  9. Pancreatic Cancer and Smoking • Dose relationship with number of cigarettes smoked • N-nitroso compounds may trigger hyperplastic and proliferative changes in pancreatic ducts • Pancreatic cancer occurs in smokers 10 years earlier than in non-smokers • 25% of pancreatic cancers attributable to smoking • Risk returns to that of non-smokers 15 years after smoking cessation

  10. NET and Smoking A. Colar et al, ENET 2008

  11. Pancreatic Cancer Diet Increased RiskProtective High intake of meat Fresh fruits and fat and vegetables

  12. National Institutes of Health - AARP • 302 060 persons followed for 5 years (1995-2000) • 654 pancreatic cancers Am J Epidemiol2008; 176:586-597

  13. Am J Epidemiol 2008; 176:590

  14. Coffee and cancer of the pancreas B MacMahon, S Yen, D Trichopoulos, K Warren, and G Nardi We questioned 369 patients with histologically proved cancer of the pancreas and 644 control patients about their use of tobacco, alcohol, tea, and coffee. There was a weak positive association between pancreatic cancer and cigarette smoking, but we found no association with use of cigars, pipe tobacco, alcoholic beverages, or tea. A strong association between coffee consumption and pancreatic cancer was evident in both sexes. The association was not affected by controlling for cigarette use. For the sexes combined, there was a significant dose-response relation (P approximately 0.001); after adjustment for cigarette smoking, the relative risk associated with drinking up to two cups of coffee per day was 1.8 (95% confidence limits, 1.0 to 3.0), and that with three or more cups per day was 2.7 (1.6 to 4.7). This association should be evaluated with other data; if it reflects a causal relation between coffee drinking and pancreatic cancer, coffee use might account for a substantial proportion of the cases of this disease in the United States. NEJM March 12, 1981 Vol. 304:630-633

  15. Other risk factors for pancreatic cancer identified in various case-control studies • Diabetes mellitus • Heavy alcohol consumption?

  16. New onset diabetes mellitus above the age of 50 years: 1% will develop pancreatic cancer within the next 3 years

  17. ERCP

  18. Pancreatic Cancer Chronic Pancreatitis NEJM 1993, 328:1430 • 56 cancers in 2015 patients • Expected number: 2 • 20fold increase • After 20 years of chronic pancreatitis:risk of cancer 4%

  19. Chronic Pancreatitis Avanitakis M, Endoscopy 2004;36:535 K-ras (proto-oncogene located on chromosome 12p12) Gene mutation in chain of events leading to ductal adenocarcinoma ___________________________________ Pancreatic duct brushings: K-ras mutation found in 57 of 146 patients (38%) Follow-up (3.5 yrs) in 112 pts: Ca in 4 of 44 with mutation, in 0 of 68 without mutation

  20. Kindred followed at the Mayo Clinic

  21. Hereditary PancreatitisPathophysiology Mutated cationic trypsinogen When activated to trypsin, cannot be inactivated by trypsin-like serine proteases that slice proteins at arginine and lysine residues

  22. Hereditary Pancreatitis Cancer risk 50 - 70fold increased. At age 70, cumulative risk of 40%

  23. 25% of patients with Zollinger-Ellison syndrome have MEN-I Risk also increased in von Hippel-Lindau disease

  24. Family History of Pancreatic Cancer Familial Pancreatic Cancer (FPC) Pair of first-degree relatives with pancreatic cancer Germline mutations identified: CDKN2A, BRCA2, PALB2, STK11 and PRSS1

  25. 9040 persons with pancreatic cancer in 1718 kindreds enrolled in National Familial Pancreas Tumor Registry FPC kindred members 6.8x risk SPC* kindred members 2.4x risk *Sporadic pancreatic cancer Brune KA, J. Natl. Cancer Inst 2010; 102, 119-126

  26. FPC: Young onset kindred member (< 50 yrs)Risk 9.3 x No young onset kindred memberRisk 6.3x (No such difference in SPC kindreds) Brune KA, J. Natl. Cancer Inst 2010; 102, 119-126

  27. Cancer of the Bile Ducts J. Hep 2002;36:321 Risk Factor Primary sclerosing cholangitis (PSC) 609 patients with PSC, 6-year follow-up: 13% developed cholangiocarcinoma annual risk 1.5%

  28. PSC: 14fold increased risk of pancreatic cancer

  29. Armory in Graz

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