Tumor necrosis factor alpha and interferon gamma genes polymorphisms and serum levels in pancreatic adenocarcinoma.

Several biochemical pathways can lead to cancer cachexia, one of which involves the elevation of the cytokines, such as tumor necrosis factor alpha (TNF-alpha) and interferon gamma (INF-gamma). It was suggested that TNF-alpha and INF-gamma genes polymorphisms may influence these cytokines serum levels, but published data are still controversial. The aim of our study was to assess the clinical significance of -308G/A TNF-alpha and +874A/T INF-gamma genes polymorphisms as well as TNF-alpha and INF-gamma serum levels in pancreatic adenocarcinoma (PA) and chronic pancreatitis (CP) as regards to healthy volunteers. We studied 41 patients with pancreatic adenocarcinoma, 56 with chronic pancreatitis and 50 healthy volunteers. Peripheral venous blood samples were obtained from all patients for TNF-alpha and INF-gamma serum concentrations measurement. After DNA isolation TNF-alpha and INF-gamma genes polymorphisms have been studied using restriction fragment length polymorphism (RFLP) analysis. Plasma levels of TNF-alpha were significantly higher in PA patients (32.7 pg/ml) compared with CP patients (3.2 pg/ ml) and control group (<1.6 pg/ml; p<0.01). Similarly, plasma levels of INF-gamma in PA patients (12.7 pg/ml) were higher from those in CP and control group (<7.1 pg/ml; p<0.01). In contrast, there were no differences between CP patients and healthy volunteers in INF-gamma levels. We observed a trend toward a correlation between weight loss in PA patients and TNF-alpha serum level (p=0.02). The TNF-alpha and INF-gamma genotype distribution were similar in patients with PA, CP and control group. We have not observed any association between TNF-alpha and INF-gamma serum levels and their genes polymorphisms. Our results suggest that elevated TNF-alpha serum level may have clinical significance in the development of cachexia in PA patients. -308G/A TNF-alpha and +874A/T INF-gamma genes polymorphisms probably do not play important role in pancreatic diseases. Key words: pancreatic adenocarcinoma, tumor necrosis factor alpha, interferon gamma, cytokines, polymorphism.