The Role of Genetic Factors in the Etiology of Pancreatic Adenocarcinoma: An Update

Abstract

Pancreatic cancer is a disease with a very poor prognosis and its etiology is still largely elusive. The only consistent environmental risk factor is cigarette smoking. A previous history of pancreatitis or diabetes mellitus is also considered to be a risk factor. Epidemiological studies have confirmed that relatives of those with pancreatic cancer have an increased risk of this malignancy, and it has been evaluated that 3–5% of all pancreatic cancer cases are caused by genetic predisposition to the disease. Usually this occurs in the setting of a known inherited cancer syndrome caused by mutations in genes such as BRCA1/2 and CDKN2A. Whether or not a true site-specific pancreatic adenocarcinoma syndrome exists is not known. The real challenge for the management of high risk patients is to develop new screening methods than can identify pre-neoplastic or early neoplastic lesions in a timely manner.

NOTE ADDED IN PROOF

Lal et al. recently screened for CDKN2A, BRCA1 and BRCA2 germline mutations a series of 38 patients with pancreatic cancer considered as high or intermediate risk, based on their family history (Cancer Res. 2000, 60, 409–416). Five (13%) germline mutations were idenfied (1 CDKN2A, 4 Ashkenazi Jewish BRCA1/2 mutations). Four of the mutation carriers had strong family histories of the syndromes associated with the mutated genes. The same research team have also identified mutations in CDKN2A in 2 of 14 individuals with both pancreatic cancer and melanoma adding further weight to the previously reported association between these cancers (Genes Chromosomes Cancer 2000, 27, 358–361).