Prevalence of Selected Single-Nucleotide Variants in Patients with Neuroendocrine Tumors-Potential Clinical Relevance.

Introduction: The genetic basis of neuroendocrine tumors (NETs), whose incidence is continuously increasing, is still not fully defined. The majority of NETs are sporadic, and only a small percentage occur as part of hereditary genetic syndromes. However, the associations of multiple genetic variants have been found as clinically relevant in several neoplasms. The aim of this study was to evaluate whether selected, literature-based genetic variants may have a potential role in NET susceptibility and clinical outcome in Polish patients.

Materials/methods: A total of 185 patients recruited from one clinical center were enrolled. In the first part of the study, the molecular analysis including four single-nucleotide variants (rs8005354 (, NM_001344 intronic T/C substitution), rs2069762 (T/G substitution in the promoter region of the NM_000586), rs3731198 (, NM_000077 intronic A/G substitution), and rs1800872 (C/A substitution in the promoter region of the NM_000572)) was performed in 107 participants (49 patients with NETs with different primary site NETs and a control group of 58 healthy adult volunteers). In the second stage, the same single-nucleotide polymorphisms (SNPs) were assessed in 127 patients with NET and analyzed in terms of clinical data (primary site, serum CgA concentration, and metastatic disease).

Results: The analysis of homozygotes revealed a statistically significant higher prevalence of TT homozygotes of variant rs3731198 in the control group ( = 0.0209). In NET patients, there was a statistically significant higher prevalence of GG homozygotes of variant rs1800872 ( = 0.003). There was a statistically significant correlation between the rs3731198 variant and lymph node metastases ( = 0.0038 with Bonferroni correction).

Conclusions: Our study indicates that GG homozygotes of variant rs1800872 are more often observed in NET patients, while TT homozygotes of variant rs3731198 are less frequent in this group. The rs3731198 variant may be related to an increased risk of lymph node metastasis. Further, larger multicenter studies are warranted to evaluate the potential genetic factors of sporadic NETs.