Public Health Challenge

Pancreatic cancer is the 4th leading cause of cancer deaths in the US in men and women, and represents about 2 percent of all cancer diagnoses world-wide. The average age on onset is 71 years of age. Many of the signs and symptoms of pancreatic cancers are not very specific to the disease itself. There are no reliable screening tests available for pancreatic cancer, which is why it is diagnosed late. Genes play an important role in the development of pancreatic cancer and individuals who carry susceptibility genes are at increased risk for developing the disease.

Research Findings

The most well established factor for risk of pancreatic cancer is cigarette smoking, followed by family history, obesity, diabetes, chronic pancreatitis, dietary fat and physical activity. Like all cancers, pancreatic cancer arises due to a series of genetic mutations, which are either acquired or inherited.

Possible Directions

INHERITED GENE CHANGES-- Individuals with a family history of pancreatic cancer are at an increased risk of developing pancreatic cancer. In particular, individuals from familial pancreatic cancer kindreds who have at least one first degree relative with pancreatic cancer have a 9-fold increased risk of developing pancreatic cancer themselves. Several known genetic syndromes have been associated with an increased risk of pancreatic cancer, these include, hereditary breast and ovarian cancer due to mutations in BRCA2, Familial Melanoma due to mutations in CDKN2A and Peutz-Jeghers syndrome due to mutations in LBK1. The genes responsible for the majority of the clustering of pancreatic cancer in families remain unclear. However, a recently developed risk prediction tool, PancPRO, has been shown to provide accurate risk assessment in high-risk families. These tools can help identify individuals at high risk who may benefit from early detection screening and/or genetic testing. ACQUIRED GENE CHANGES-- The recently completed pancreatic cancer genome project has greatly increased our understanding of the genetic changes that cause pancreatic cancer to develop. This study, which examined the changes in genetic sequence, genetic structure and gene expression identified 12 core pathways that when disrupted lead to the development of pancreatic cancer.

Future Research Opportunities

A multi-center screening study using a similar Endoscopic Ultrasound (EUS)-based strategy (and CT and MRI) for individuals with a strong inherited predisposition to develop pancreatic cancer as indicated by their family history or inherited mutations is ongoing. Gene discovery studies using a variety of methods are underway to identify the specific inherited changes that predispose to pancreatic cancer.