TNF-alpha promoter single nucleotide polymorphisms in gastroenteropancreatic neuroendocrine tumors

Abstract

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) secrete biogenic amines, hormones and growth factors, tumor necrosis factor-alpha (TNF-alpha) being one of them. As the expression of TNF-alpha is mostly regulated at the transcriptional level, its promoter polymorphisms have been intensively studied as a potential determinant of TNF-alpha production and cancer susceptibility. We have analyzed for the first time the potential association between -238, -308, -857 and -1031 TNF-alpha promoter polymorphisms and GEP-NETs. The study included 65 individuals diagnosed with GEP-NET and 154 healthy age- and sex-matched controls. Although most of the patients had solitary GEP-NETs, 6 were diagnosed with GEP-NET as a part of multiple endocrine neoplasia type 1 and 1 as a part of neurofibromatosis type 1. The C allele at the -1031 position was more frequent in GEP-NET patients (p < 0.0005), suggesting its possible role in GEP-NET development. The significant difference between foregut and midgut GEP-NET patients was observed in the -308 high expression genotypes and -308A allele (high expression) which tend to occur more frequently in the foregut GEP-NETs (p = 0.0392 and p = 0.0350, respectively). When functional and nonfunctional pancreatic endocrine tumors were compared, there were no significant differences in the researched TNF-alpha SNPs. The results suggest the putative role of TNF-alpha -1031 polymorphism in the development of GEP-NET.