Environmental Risk Factors for Chronic Pancreatitis and Pancreatic Cancer

Abstract

Chronic pancreatitis has long been thought to be mainly associated with immoderate alcohol consumption. The observation that only ∼10% of heavy drinkers develop chronic pancreatitis not only suggests that other environmental factors, such as tobacco smoke, are potent additional risk factors, but also that the genetic component of pancreatitis is more common than previously presumed. Either disease-causing or protective traits have been indentified for mutations in different trypsinogen genes, the gene for the trypsin inhibitor SPINK1, chymotrypsinogen C, and the cystic fibrosis transmembane conductance regulator (CFTR). Other factors that have been proposed to contribute to pancreatitis are obesity, diets high in animal protein and fat, as well as antioxidant deficiencies. For the development of pancreatic cancer, preexisting chronic pancreatitis, more prominently hereditary pancreatitis, is a risk factor. The data on environmental risk factors for pancreatic cancer are, with the notable exception of tobacco smoke, either sparse, unconfirmed or controversial. Obesity appears to increase the risk of pancreatic cancer in the West but not in Japan. Diets high in processed or red meat, diets low in fruits and vegetables, phytochemicals such as lycopene and flavonols, have been proposed and refuted as risk or protective factors in different trials. The best established and single most important risk factor for cancer as well as pancreatitis and the one to clearly avoid is tobacco smoke.

Pancreatic Cancer: Yesterday, Today and Tomorrow

“…Smoking is the most important environmental risk factor for pancreatic cancer [18], while obesity has been associated with a higher incidence of pancreatic cancer in epidemiological studies [19]. The etiological role of alcohol in pancreatic cancer has been hard to ascertain because of the close association between alcohol and chronic pancreatitis, a known risk factor for pancreatic cancer [20].…”

“…At the microscopic level, ductal adenocarcinomas form more or less well defined duct structures, and are embedded in an extensive, fibrotic stroma ( Figure 4B). Immunohistochemically, pancreatic cancers may express CEA, CA 19-9, CA125, SMAD4, as well as cytokeratins (CK 5/6,7,8,18,and 19) and mucins (MUC1, MUC4, MUC5AC, and MUC6). Increasing tumor size and invasion correlate with poor patient survival [74].…”

Association Between Pancreatitis and Subsequent Risk of Pancreatic Cancer: a Systematic Review of Epidemiological Studies

“…Of these, cigarette smoking has been regarded as the most important risk factor. Smokers have 2-fold to 3-fold increased risk of PC compared to non-smokers with cigarette smoking accounting for approximately a quarter of PC incidence Silverman et al, 1994;Fuchs et al, 1996;Lowenfels et al, 2006;Ko et al, 2007;Bao et al, 2009;Talamini et al, 2010;Nitsche et al, 2011). Hereditary PC accounts for 5%-10% of all cases.…”

Influence of the c.1517G>C genetic variant in the XRCC1 gene on pancreatic cancer susceptibility in a Chinese population

“…It is well known that genetic factors play key roles in PC pathogenesis (Lin et al, 2001;Lowenfels and Maisonneuve, 2003;Duell et al, 2008;Landi, 2009;Chu et al, 2010;Nitsche et al, 2011). It has also been suggested that the XRCC1 gene is one of the most important candidate genes influencing the susceptibility to PC (Duell et al, 2002;Li et al, 2006Li et al, , 2007McWilliams et al, 2008;Nakao et al, 2012), and its genetic polymorphisms are involved in modulating PC risk (Duell et al, 2002;Hung et al, 2005;Li et al, 2006;Mandal et al, 2010).…”