title: Interleukin 1 beta gene promoter SNPs are associated with risk of pancreatic cancer.
abstract: Epidemiological and experimental data demonstrate, that inflammation contributes significantly to pancreatic carcinogenesis. IL1beta, a pleiotropic cytokine produced by inflammatory cells and tumor cells, promotes cancer progression. Single nucleotide polymorphisms (SNPs) of the IL1beta promoter were found to be associated with an increased risk for certain cancers. In this case-control study we determined IL1beta promoter SNPs in 73 patients with pancreatic cancer and 235 controls. We found that the IL1beta -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 IL1beta -511/-31 genotypes (p=0.0323). Furthermore, the IL1beta -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 IL1beta -511CT/-31TC alleles define an IL1beta secretory phenotype in pancreatic cancer cell lines in vitro. These findings provide a first evidence for an association of the IL1beta gene promoter SNPs with risk for pancreatic cancer.
authors.affiliation: Technische Universität of München, II. Medizinische Klinik, Klinikum rechts der Isar, Ismaninger Str. 22, 81675 Munich, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Hamacher
authors.forename: Sandra
authors.initials: S
authors.lastname: Diersch
authors.forename: Melanie
authors.initials: M
authors.lastname: Scheibel
authors.forename: Florian
authors.initials: F
authors.lastname: Eckel
authors.forename: Martina
authors.initials: M
authors.lastname: Mayr
authors.forename: Roland
authors.initials: R
authors.lastname: Rad
authors.forename: Monther
authors.initials: M
authors.lastname: Bajbouj
authors.forename: Roland M
authors.initials: RM
authors.lastname: Schmid
authors.forename: Dieter
authors.initials: D
authors.lastname: Saur
authors.forename: Günter
authors.initials: G
authors.lastname: Schneider
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012307:Risk Factors
chemical_list: D053583:Interleukin-1beta