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Epidemiological and experimental data demonstrate, that inflammation contributes significantly to pancreatic carcinogenesis. IL1β, a pleiotropic cytokine produced by inflammatory cells and tumor cells, promotes cancer progression. Single nucleotide polymorphisms (SNPs) of the IL1β promoter were found to be associated with an increased risk for certain cancers. In this case-control study we determined IL1β promoter SNPs in 73 patients with pancreatic cancer and 235 controls. We found that the IL1β −511CT/−31TC genotype was significantly associated with an increased risk for pancreatic cancer (OR 1.42, p = 0.0456). Among pancreatic cancer cases, patients with the −511CT/−31TC genotype had less frequently resectable disease than patients with other IL1β −511/−31 genotypes (p = 0.0323). Furthermore, the IL1β −511CT/−31TC genotype was more frequent observed in UICC stage IV (p = 0.039) and undifferentiated tumors (G3) (p = 0.019). In addition, we found that the proinflammatory IL1β −511CT/−31TC alleles define an IL1β secretory phenotype in pancreatic cancer cell lines in vitro. These findings provide a first evidence for an association of the IL1β gene promoter SNPs with risk for pancreatic cancer.