What are the occurrence rates and risk factors of pancreatic cancer?

Occurrence Rates and Risk Factors of Pancreatic Cancer

Pancreatic cancer has an age-standardized incidence rate of approximately 10-12 cases per 100,000 population in Western countries, with higher rates in men than women, and is associated with a dismal prognosis where mortality rates nearly equal incidence rates due to late diagnosis and poor treatment response. 1

Global Incidence and Mortality

Incidence Rates

• In Europe, pancreatic cancer is the 7th most frequent cancer, accounting for 2.8% of cancers in men and 3.2% in women 1
• Annual incidence rates in Europe:
  • Men: 11.6 per 100,000 (range: 4.7 in Cyprus to 17.2 in Hungary) 1
  • Women: 8.1 per 100,000 (range: 2.1 in Cyprus to 11.4 in Finland) 1
• In the USA, the SEER program showed a decline in total incidence from 12.3 per 100,000 in 1973 to 10.7 per 100,000 in 1999 1
• Worldwide, over 458,918 new cases were reported in 2018 2

Mortality Rates

• Fifth leading cause of cancer-related death in Europe with approximately 70,000 deaths annually 1
• Predicted to become the fourth cause of cancer death in both sexes in the European Union 1
• Extremely high fatality rate with >95% of affected individuals dying of the disease 1
• Five-year survival rate remains at only 9% 2

Age and Gender Distribution

• Incidence increases steeply with age:
  • 1.5 per 100,000/year in patients aged 15-44 years
  • 55 per 100,000/year in patients >65 years of age 1
• 80% of cases occur in the 60-80 year age group 1
• Men have approximately 50% higher age-adjusted incidence rate than women 1

Anatomical Distribution

• 75% of ductal pancreatic carcinomas occur within the head or neck of the pancreas
• 15-20% in the body of the pancreas
• 5-10% in the tail of the pancreas 1

Major Risk Factors

Established Risk Factors

1. Cigarette smoking:

   • Most consistently identified risk factor 1
   • Accounts for approximately 25-30% of all cases 1, 3
   • Relative risk of 2.0 with an attributable fraction of 11-32% 3

2. Chronic pancreatitis:

   • Associated with a 5-15 fold increased risk 1, 3
   • Hereditary pancreatitis carries a 50-70 fold increased risk 1, 3
   • Cumulative lifetime risk to age 75 years of 40% in hereditary pancreatitis 1

3. Diabetes mellitus:

   • Particularly adult-onset diabetes of less than two years' duration 1
   • Relative risk of 1.4-2.2 3
   • Can be both a risk factor and an early manifestation of pancreatic cancer 4

4. Obesity and metabolic syndrome factors:

   • Relative risk of 1.2-1.5 3, 5
   • Associated with increased pancreatic cancer risk in recent cohort studies 6

5. Genetic factors:

   • 5-10% of patients have an underlying germline disorder 1, 5, 7
   • Familial pancreatic cancer shows an 18-fold increased risk in families with an affected first-degree relative 1
   • Non-O blood group is associated with increased risk 5

6. Other established risk factors:

   • Helicobacter pylori infection (relative risk of 1.5) 3, 5
   • High consumption of processed meat and red meat (relative risk of 1.1-1.5) 1, 3
   • Heavy alcohol intake (relative risk of 1.1-1.5) 3, 5

Genetic Syndromes Associated with Increased Risk

• Hereditary pancreatitis syndrome
• Hereditary non-polyposis colorectal cancer (HNPCC)
• Hereditary atypical multiple mole melanoma syndrome
• Hereditary BRCA2-related breast and ovarian cancer
• Peutz-Jeghers syndrome
• Familial adenomatous polyposis (FAP) 1

Clinical Implications and Prevention

Screening

• No efficient screening tools available for general population 1
• Targeted screening recommended only for high-risk populations:
  • Those with hereditary conditions
  • Regular endoscopic ultrasound (EUS) and MRI recommended for high-risk individuals 1

Prevention Strategies

• Smoking cessation - risk reduction observed within a decade after quitting 6
• Maintaining healthy weight and physical activity 3, 5
• Consuming at least five servings of vegetables and fruits daily 3
• Avoiding heavy alcohol consumption 5

Clinical Presentation

• Often diagnosed late due to lack of early symptoms 1
• Common presenting symptoms:
  • Jaundice (predominant in head of pancreas tumors)
  • Abdominal or back pain (predominant in body and tail tumors)
  • Weight loss
  • New-onset diabetes (in up to 10% of patients) 1

Diagnostic Challenges

• Late diagnosis due to asymptomatic early disease and non-specific symptoms 1
• Difficult differentiation between focal chronic pancreatitis and pancreatic cancer 3
• Standard tumor markers like CA 19-9 may be normal in pancreatic cancer 3

The high mortality rate of pancreatic cancer underscores the importance of risk factor modification and targeted surveillance in high-risk populations, as early detection remains challenging and treatment options for advanced disease remain limited.