Hamacher Rainer, Diersch Sandra, Scheibel Melanie, Eckel Florian, Mayr Martina, Rad Roland, Bajbouj Monther, Schmid Roland M, Saur Dieter, Schneider Günter
Technische Universität of München, II. Medizinische Klinik, Klinikum rechts der Isar, Ismaninger Str. 22, 81675 Munich, Germany.
Cytokine. 2009 May;46(2):182-6. doi: 10.1016/j.cyto.2009.01.005. Epub 2009 Feb 28.
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.
流行病学和实验数据表明，炎症在胰腺癌的发生过程中起着重要作用。白细胞介素1β（IL1β）是一种由炎症细胞和肿瘤细胞产生的多效性细胞因子，可促进癌症进展。研究发现，IL1β启动子的单核苷酸多态性（SNP）与某些癌症的风险增加有关。在这项病例对照研究中，我们测定了73例胰腺癌患者和235例对照者的IL1β启动子SNP。我们发现，IL1β -511CT/-31TC基因型与胰腺癌风险增加显著相关（比值比1.42，p = 0.0456）。在胰腺癌病例中，-511CT/-31TC基因型患者的可切除性疾病发生率低于其他IL1β -511/-31基因型患者（p = 0.0323）。此外，IL1β -511CT/-31TC基因型在国际抗癌联盟（UICC）IV期（p = 0.039）和未分化肿瘤（G3）（p = 0.019）中更为常见。此外，我们发现促炎的IL1β -511CT/-31TC等位基因在体外可定义胰腺癌细胞系中的IL1β分泌表型。这些发现首次证明了IL1β基因启动子SNP与胰腺癌风险之间的关联。
