Role of cyclooxygenase-2 gene polymorphisms in pancreatic carcinogenesis

AIM:To evaluate the clinical significance of-765G/C and-1195G/A cyclooxygenase-2 (COX-2) gene polymorphisms in patients with pancreatic cancer (PC).METHODS:The study included 201 patients:85 with PC and 116 healthy controls.-765G/C and-1195G/A COX-2 gene polymorphisms were studied in DNA isolated from blood samples.The associations of the analyzed genotypes and clinical data at diagnosis were evaluated.RESULTS:We found an increased frequency of the homozygous-1195AA COX-2 genotype in patients with PC (53.7%) compared with the control group (21%) (P < 0.01).In contrast,the distribution of genotypeand allele frequencies of the-765G/C COX-2 polymorphism in the PC patients were not different from those in control groups.A correlation between presence of homozygous-1195AA COX-2 genotype and tumor size > 3 cm was observed (P < 0.05).Analyzed polymorphisms were unrelated to the patients' sex and age,nor to the presence of regional or distant metastases.CONCLUSION:These preliminary results indicate that the-1195G/A COX-2 polymorphism may play an important role in PC prognosis and carcinogenesis.

Utility of different serum fibrosis markers in diagnosing patients with chronic pancreatitis and pancreatic adenocarcinoma

AIM: To estimate the levels of serum cytokines in chronic pancreatitis(CP) and pancreatic ductal adenocarcinoma(PDAC) patients in order to evaluate their usefulness as possible biomarkers.METHODS: The study included 167 Caucasian patients: 74 with PDAC(28 men and 42 women, aged 30-88 years), 78 with CP(50 men and 21 women, aged 20-79 years) and 15 age-matched healthy controls hospitalized in the Department of Digestive Tract Diseases, Medical University of Lodz, Poland between 2006 and 2013. Serum MCP-1, transforming growth factor(TGF)-β1, HA and s-Fr were measured in patients with CP(n = 78), PDAC(n = 74) and healthy controls(n = 15) using ELISA(Corgenix United Kingdom Ltd R and D Systems). The severity of CP was assessed according to the Cambridge classification.RESULTS: Both patients with CP and PDAC had a significantly higher mean TGF-β1 serum level(1066 ± 582and 888 ± 356 vs 264 ± 93, P < 0.0001), mean s-Fr(2.42 ± 1.385 and 2.41 ± 1.275 vs 0.6 ± 0.370, P < 0.0001) and mean HA(199 ± 254 and 270 ± 358 vs 40 ± 26, P < 0.0001) compared to controls. There was no difference in mean MCP-1 between all the groups. There were no significant differences in any cytokine levels between the PC and PDAC groups. No significant differences between serum cytokines depending on age, gender or smoking status were found in CP patients. Mean s-Fr concentration was significantly higher in CP, lasting longer than 5 years compared to those with a shorter disease clinical course(2.639 ± 1.125 vs 1.870 ± 0.970, P < 0.03). There was no correlation between tumor size, localization or TNM classification and serum TGF-β1, MCP-1, s-Fr and HA levels in patients with PDAC. No significant differences between cytokines depending on diabetes presence in CP were found. Nevertheless, mean serum TGF-β1 concentration in PDAC patients was higher in those with diabetes compared to the remaining group(986 vs 839, P = 0.043). CONCLUSION: Serum TGF-β1, s-Fr and HA may be considered additional diagnostic markers of CP and PDAC. TGF-β1 may be useful to predict endocrine insufficiency in PDAC.