IL-2-330 T/G SNP and serum values-potential new tumor markers in neuroendocrine tumors of the gastrointestinal tract and pancreas (GEP-NETs)

Cytokines participate in tumorigenesis of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Single nucleotide polymorphisms (SNPs) in cytokine genes influence expression of proteins and are evaluated in cancer susceptibility. The aim of this study was to evaluate IL-2 -330 T/G SNP and susceptibility to GEP-NETs, and analyze the correlation between G-allele and IL-2 serum values in GEP-NET patients. Moreover we assessed the value of IL-2 as a tumor serum marker. IL-2 -330 T/G SNP was examined in 101 patients and 150 healthy volunteers and IL-2 serum levels in patients and 20 controls. Patients' IL-2 serum levels were compared to IL-2 -330 T/G genotypes and tumor functional status and finally with known markers such as chromogranin A (CgA) and 5-hydroxyindolacetic acid (5-HIAA). There was a significant difference in genotype distribution of the IL-2 -330 polymorphisms between GEP-NET and control group (p = 0.0006) as well as in the frequency of G-allele (p = 0.010). G-allele correlated with higher IL-2 serum levels (p = 0.028) and elevated in all patients, being highest in patients with functional tumors (p = 0.039). Compared to CgA and 5-HIAA, IL-2 was more specific in detecting GEP-NET patients (p < 0.0001 and p < 0.0001, respectively). Our results indicate importance of IL-2 in GEP-NET development and biochemical diagnosis.