PANCREATIC CANCER

Pancreatic cancer is the fifth leading cause of cancer death in the United States. In the year 2009, an estimated 42,470 new cases are expected to be diagnosed, and 35,240 deaths are expected to occur.

Incidence and epidemiology

Gender
The incidence of pancreatic cancer is slightly higher in males than in females. These gender differences are most prominent among younger individuals.

Age
The peak incidence of pancreatic carcinoma occurs in the seventh decade of life. Two-thirds of new cases occur in people > 65 years old.

Race
The incidence of pancreatic cancer is higher in the black population, with an excess risk of 40% to 50% over that in whites. Perhaps more importantly, black males probably have the highest risk of pancreatic cancer worldwide.

Survival
Cancer of the pancreas is a highly lethal disease historically, with few reports of 5-year survivors. However, more recent series have shown a decrease in both operative mortality and overall morbidity. There has also been a significant increase in 5-year survival after curative resection (21%–25%). Factors that appear to be important in predicting long-term survival after resection include clear surgical margins, small tumor size (< 2 cm), negative lymph nodes, and reduced perioperative mortality.

Adenocarcinoma of the pancreas, the most common histologic type, has a median survival of 9 to 12 months and an overall 5-year survival rate of 3% for all stages. At the time of diagnosis, over 50% of patients with pancreatic adenocarcinoma have clinically apparent metastatic disease. Among patients whose disease is considered to be resectable, 50% will die of a recurrent tumor within 2 years.

Etiology and risk factors

The specific risk factors for pancreatic cancer are not as striking as those for other gastrointestinal (GI) malignancies, such as esophageal and gastric carcinomas. There does, however, appear to be a significant relationship between pancreatic cancer and environmental carcinogens.

Cigarette smoking
Cigarette smoke is one of the carcinogens directly linked to the causation of pancreatic malignancies. Heavy cigarette smokers have at least a twofold greater risk of developing pancreatic carcinoma than nonsmokers. In Japan, cigarette smoking carries an even greater risk, which can be as much as 10-fold in men smoking one to two packs of cigarettes daily.

N-nitroso compounds
These compounds, found particularly in processed meat products, reliably induce pancreatic cancer in a variety of laboratory animals. No study has directly linked dietary carcinogens to pancreatic cancers in humans.

Caffeine
The contribution of caffeine consumption to the development of pancreatic carcinoma is controversial. A case-controlled study showed a correlation between caffeine consumption and pancreatic cancer. However, other studies have been unable to confirm this relationship.

Alcohol
A clear-cut relationship between alcohol use and pancreatic carcinoma has not been shown.

Diabetes
Hyperglycemia does not seem to be a risk factor for pancreatic cancer. However, 10% of all patients with pancreatic carcinoma present with new-onset diabetes.

Genetic factors
Cancer of the pancreas is a genetic disease. To date, more than 80% of resected pancreatic cancers have been found to harbor activating point mutations in KRAS. In addition, the tumor-suppressor genes CDKN2A, TP53, and DPC4 are all frequently inactivated in this cancer.