IL-6-174 C/G polymorphism in the gastroenteropancreatic neuroendocrine tumors (GEP-NETs)

Abstract

IL-6 is a pleiotropic cytokine with still controversial role in tumorigenesis of different cancer types. Its promoter SNP- 174 C/G is associated with increased IL-6 transcription and in some tumor types with elevated IL-6 serum levels. The role of IL-6 polymorphisms and IL-6 serum values and their correlation in the gastroenteropancreatic neuroendocrine tumors is lacking. We investigated for the first time frequencies of IL-6-174 genotypes in 80 GEP-NET patients and 162 age- and sex-matched healthy controls, serum values of IL-6 in GEP-NET patients and their correlation with IL-6-174 genotypes. To analyze IL6-174 C/G polymorphism PCR- NlaIII RFLP method was used, and serum levels were measured on Immulite analyzer by enzymatic solid-phase chemiluminescent immunometric method. Serum IL-6 values were elevated (> 5.9 pg/ml) in 36.8% GEP-NET patients. Differences in genotypes distribution between patients and healthy controls as well as between patients with gastrointestinal and pancreatic neuroendocrine tumors (PETs) and functioning and nonfunctioning PETs were tested by χ 2 test and Fisher's Exact test. Analysis of variance (ANOVA with proc GLM in SAS/Stat) was performed for the group comparison. Level of significance was α = 0.05. Patients with nonfunctioning PETs had only high expression IL-6-174 CG and GG genotypes and according to genotypes differed significantly ( p = 0.0289) from functioning PETs. High serum IL-6 values in all GEP-NET patients correlated significantly with GG IL-6-174 genotype ( p = 0.0139). Nonfunctioning PET patients had significantly ( p = 0.000777) higher IL-6 serum values in comparison to patients with functioning PETs and gastrointestinal NETs. Serum IL-6 values correlated significantly with IL-6-174 genotypes in nonfunctioning PETs and gastrointestinal NETs ( p < 0.05), but not in functioning PETs.