engleski

TNF-alpha promoter SNP -1031 C is associated with susceptibility for gastroenteropancreatic neuroendocrine tumors (GEP-NETS)

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare, heterogeneous group of tumors secreting biogenic amines, hormones and growth factors, among which tumor necrosis factor alpha (TNF-&#945; ). As the expression of TNF-&#945; is mostly regulated at the transcriptional level, promoter polymorphisms of its gene, leading to aberrant TNF-&#945; production and possibly cancer susceptibility have intensively been studied. We have analyzed for the first time the potential association between -238, -308, -857 and -1031 TNF-&#945; promoter polymorphisms and GEP-NETs. The study included 65 individuals diagnosed with GEP-NET and 154 healthy age and sex matched controls. Most of the patients had solitary GEP-NETs, while six had neuroendocrine tumors as a part of multiple endocrine neoplasia type 1 (MEN-1) and one as a part of neurofibromatosis type 1 (NF-1). The C allele at the -1031 position was more frequent in GEP-NET patients (p<0.0005) suggesting its putative role in GEP-NET development. The significant difference between forgut 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 forgut GEP-NETs (p=0.0392 and p=0.0350 respectively). No differences were observed in the frequencies of -238A or -857T alleles between GEP-NET patients and healthy controls. The results suggest the putative role of TNF-&#945; -1031 polymorphism in the development of GEP-NET.

TNF-alpha; GEP-NETs

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