BRCA2 and pancreatic cancer.

Many factors, including a family history of cancer, have been implicated in the development of pancreatic cancer. Among these factors, germline BRCA2 mutations have been clearly associated with the development of this disease, while mutations in BRCA1 appear to have a limited role. Patients with pancreatic cancer and germline BRCA2 mutations tend to be Ashkenazi Jewish, have a younger than average age of onset, and in many cases, lack family history for breast, ovarian, or pancreatic cancers. In addition, somatic mutations of BRCA2 appear to be rare in tumors of the pancreas. The mechanism by which mutant BRCA2 contributes to development of pancreatic cancers is not well understood. However, it appears that inactivation of several independent functions of BRCA2 including regulation of gene transcription, chromatin remodeling, cell growth, DNA damage repair, and chromosomal instability may provide a pathophysiological basis for the association of BRCA2 mutations and pancreatic cancer.