What causes pancreatic cancer?
Although the exact cause for pancreatic cancer remains unknown, several risk factors, such as smoking and diets rich in red meat and fat, have been shown to increase the susceptibility to this particular cancer. It has been observed that a third of
pancreatic cancer cases occur among smokers. Therefore, smoking is regarded as the single greatest risk factor for this cancer.
Although the association between diabetes and pancreatic cancer is not known, the disease is more common among diabetics. Conditions such as chronic pancreatitis (long-term inflammation of the pancreas) have also been associated with an increased risk for pancreatic cancer. Some research data shows that exposure to certain substances, such as gasoline and dry cleaning chemicals increases the risk of this cancer.
Pancreatic cancers can arise from both the exocrine and endocrine portions of the pancreas. Of pancreatic tumors, 95% develop from the exocrine portion of the pancreas, including the ductal epithelium, acinar cells, connective tissue, and lymphatic tissue. Approximately 75% of all pancreatic carcinomas occur within the head or neck of the pancreas, 15-20% occur in the body of the pancreas, and 5-10% occur in the tail. Typically, pancreatic cancer first metastasizes to regional lymph nodes, then to the liver, and less commonly, to the lungs. It can also directly invade surrounding visceral organs such as the duodenum, stomach, and colon.
The molecular genetics of pancreatic adenocarcinoma have been well studied. Of these tumors, 80-95% have mutations in the KRAS2 gene, and 85-98% have mutations, deletions, or hypermethylation in the CDKN2 gene. Of these cancers, 50% have mutations in TP53 and about 55% have homozygous deletions or mutations of Smad4. Some of these mutations can also be found in high-risk precursors of pancreatic cancer. For example, in chronic pancreatitis, 30% of patients have detectable mutations in TP16 and 10% have K-ras mutations. Although studies are underway, the genetic mutations associated with pancreatic adenocarcinoma are not yet clinically useful in screening for or diagnosing the disease.
As in other organs, chronic inflammation is a predisposing factor in the development of pancreatic cancer. Patients with chronic pancreatitis from alcohol, especially those with familial forms, have much higher incidence and an earlier age of onset of pancreatic carcinoma.
Exocrine cells of the pancreas can form benign tumors, although cancerous tumors occur more often. Most of these benign tumors are cystadenomas. About 95% of cancers of the exocrine pancreas are adenocarcinomas. Adenocarcinomas usually begin in the ducts of the pancreas but sometimes develop from the cells that actually produce the pancreatic enzymes (the acinar cells). Less common cancers of the exocrine pancreas include adenosquamous carcinomas, squamous cell carcinomas, and giant cell carcinomas. These types are distinguished from one another based on their appearance under the microscope.