- •The role of the epidermal growth factor family in PNET is unknown.
- •EGFR +1562 AG genotype is associated with an increased risk of PNET development.
- •Carriers of AA/AG EGF+61/HER2+1963 combination genotype are at risk of developing PNET.
- •EGFR +1562 AA genotype could be associated with the risk of insulinoma development.
- •EGF, EGFR or HER2 SNPs are not associated with the presence of metastasis.
Pancreatic neuroendocrine tumors (NETs) are rare and account for about 7% of all cancers occurring in the pancreas. The epidermal growth factor family of receptors and their ligands play an important role in the growth and progression of tumors but their role in PNET development remains unknown. We hypothesized that functional single nucleotide polymorphisms (SNPs) in the EGF, EGFR, and HER2 genes might affect individual susceptibility to PNETs development and invasion like it was shown for various other tumors.
We genotyped 68 patients with unresectable PNETs and 300 controls to evaluate the association between EGF, EGFR, and HER2 polymorphisms and susceptibility to PNETs and presence of metastases.
Genotype analysis of three SNPs EGF +61A/G (rs4444903), EGFR +1562 G/A (rs11543848), and HER2 +1963 A/G (rs1136201) showed that carriers of EGFR +1562 AG genotype and AA/AG EGF +61/HER2 +1963 genotype combination are at risk of developing PNET. Furthermore, EGFR +1562 AA genotype could be associated with the susceptibility to insulinoma development.
Our results suggest involvement of EGFR signaling pathway in etiology of PNET development.
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Published online: June 21, 2022
Accepted: June 14, 2022
Received in revised form: May 31, 2022
Received: November 17, 2021
© 2022 Published by Elsevier Inc.