Etiology of pancreatic cancer, with a hypothesis concerning the role of N-nitroso compounds and excess gastric acidity

Abstract

In the United States, pancreatic cancer is the fourth most frequent cause of cancer death in males as well as females, after lung, prostate or breast, and colorectal cancer. Each year, approximately 30 000 Americans are diagnosed with pancreatic cancer and about the same number die of it. Germline mutations in a few genes including p16 and BRCA2 have been implicated in a small fraction of cases, as has chronic pancreatitis. The one established risk factor for pancreatic cancer is cigarette smoking: current smokers have two to three times the risk of nonsmokers. Studies of dietary factors have not been entirely consistent but do suggest associations of higher risk with consumption of smoked or processed meats or with animal foods in general and lower risk with consumption of fruits and vegetables. Colonization by Helicobacter pylori appears to increase risk, and a history of diabetes mellitus may also increase risk. The purpose of this epidemiologic review is to consider the possibility that risk of pancreatic cancer is increased by factors associated with pancreatic N-nitrosamine or N-nitrosamide exposures and with chronic excess gastric or duodenal acidity. Host genetic variation in inflammatory cytokine mechanisms may also be involved in this process. Many features of the evidence bearing on the pathophysiology of pancreatic cancer appear to support connections with N-nitroso compounds and with gastric acidity.