Pancreatic Cancer Epidemiology and Risk Factors Guenter J. Krejs Medical University of Graz, Austria
Jan 03, 2016
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 carcinomacystadenocarcinomagiant-cell carcinomaintraductal papillar mucinous
neoplasm
• 10% neuroendocrine tumors
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
Cancer of the pancreas in males, age-standardized incidence rate per 100 000 population for the year 2002
Pancreatic Cancer
Incidence and mortality are practically identical
250 000 deaths per year worldwide
Ranks 8th in a worldwide listing of cancer mortality
Pancreatic Cancer
RISK FACTORS:
Smoking
High-fat diet, obesity, diabetes
Chronic pancreatitis
Hereditary pancreatitis
Primary sclerosing cholangitis
Vincent van Gogh
Smoking and Cancer
Rel. Risk
Lung 22
Lip, oral cavity, pharynx 27
Larynx 10
Esophagus 8
Bladder, kidney 3
Pancreas 2
Stomach 2
Leukemia 2
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
NET and Smoking
Neuroendocrine tumors Risk increase with smoking
Gastroenteropancreatic
(GEP NET) 30%
Thoracic 50%
A. Colar et al, ENET 2008
Pancreatic Cancer
Diet
Increased Risk Protective
High intake of meat Fresh fruits
and fat and vegetables
National Institutes of Health - AARP
• 302 060 persons followed for 5 years (1995-2000)
• 654 pancreatic cancers
Am J Epidemiol 2008; 176:586-597
Am J Epidemiol 2008; 176:590
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
Other risk factors for pancreatic cancer identified in various case-
control studies
• Diabetes mellitus
• Heavy alcohol consumption?
New onset diabetes mellitus above the age of 50 years:
1% will develop pancreatic cancer within the next 3 years
ERCP
Pancreatic Cancer
Chronic PancreatitisNEJM 1993, 328:1430
• 56 cancers in 2015 patients
• Expected number: 2
• 20fold increase
• After 20 years of chronic pancreatitis:risk of cancer 4%
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
Kindred followed at the Mayo Clinic
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
Hereditary Pancreatitis
Cancer risk 50 - 70fold increased.
At age 70, cumulative risk of 40%
25% of patients with Zollinger-Ellison syndrome have MEN-IRisk also increased in von Hippel-Lindau disease
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
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
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
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%
PSC:
14fold increased risk of pancreatic cancer
Armory in Graz