title: 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.
authors.affiliation: Department of Endocrinology, Diabetes and Metabolism, University Hospital 'Sestre Milosrdnice', Zagreb, Croatia. mberkovi@globalnet.hr
authors.forename: Maja
authors.initials: M
authors.lastname: Berković
authors.forename: Tamara
authors.initials: T
authors.lastname: Cacev
authors.forename: Vanja
authors.initials: V
authors.lastname: Zjacić-Rotkvić
authors.forename: Sanja
authors.initials: S
authors.lastname: Kapitanović
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000235:genetics*; D005787:Gene Frequency; D006801:Humans; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D014409:Tumor Necrosis Factor-alpha