The epidermal growth factor (EGF) and its receptor (EGFR) gene-gene interactions were shown to increase the susceptibility to esophageal cancer. However, the role of the EGF/EGFR pathway in the development of gastroesophageal reflux disease (GERD) and its complications (reflux esophagitis (RE), Barrett's esophagus (BE), and esophageal adenocarcinoma (EAC)) remains unclear. This association study is aimed at investigating functional EGF and EGFR gene polymorphisms, their mRNA expression in esophageal tissues, and EGF plasma levels in relation to RE, BE, and EAC development in the Central European population. 301 patients with RE/BE/EAC (cases) as well as 98 patients with nonerosive reflux disease (NERD) and 8 healthy individuals (controls) were genotyped for +61 A>G EGF (rs4444903) and +142285 G>A EGFR (rs2227983) polymorphisms using the TaqMan quantitative polymerase chain reaction (qPCR). In random subgroups, the EGF and EGFR mRNA expressions were analyzed by reverse transcription qPCR in esophageal tissue with and without endoscopically visible pathological changes; and the EGF plasma levels were determined by enzyme-linked immunosorbent assay. None of the genotyped SNPs nor EGF-EGFR genotype interactions were associated with RE, BE, or EAC development (p > 0.05). Moreover, mRNA expression of neither EGF nor EGFR differed between samples of the esophageal tissue with and without endoscopically visible pathology (p > 0.05) nor between samples from patients with different diagnoses, i.e., RE, BE, or EAC (p > 0.05). Nevertheless, the lower EGF mRNA expression in carriers of combined genotypes AA +61 EGF (rs4444903) and GG +142285 EGFR (rs2227983; p < 0.05) suggests a possible direct/indirect effect of EGF-EGFR gene interactions on EGF gene expression. In conclusion, EGF and EGFR gene variants and their mRNA/protein expression were not associated with RE, BE or EAC development in the Central European population.

2nd Department of Internal Medicine Gastroenterology and Geriatrics University Hospital Olomouc Faculty of Medicine and Dentistry Palacky University 1 P Pavlova 6 779 00 Olomouc Czech Republic

3rd Department of Surgery 1st Faculty of Medicine Charles University and Motol University Hospital 5 Uvalu 84 150 06 Prague Czech Republic

Central European Institute of Technology Masaryk University Kamenice 735 5 625 00 Brno Czech Republic

Clinic of Maxillofacial Surgery Institution Shared with University Hospital Brno Faculty of Medicine Masaryk University Jihlavska 20 625 00 Brno Czech Republic

Clinic of Stomatology Institution Shared with St Anne's University Hospital Faculty of Medicine Masaryk University Pekarska 664 53 602 00 Brno Czech Republic

Department of Burns and Plastic Surgery Institution Shared with University Hospital Brno Faculty of Medicine Masaryk University Jihlavska 20 625 00 Brno Czech Republic

Department of Gastroenterology and Digestive Endoscopy Masaryk Memorial Cancer Institute Zluty Kopec 7 656 53 Brno Czech Republic

Department of Gastroenterology and Internal Medicine Institution Shared with University Hospital Brno Faculty of Medicine Masaryk University Jihlavska 20 625 00 Brno Czech Republic

Department of Medical Biology Faculty of Medicine Masaryk University Kamenice 735 5 625 00 Brno Czech Republic

Department of Pathology Institution Shared with University Hospital Brno Faculty of Medicine Masaryk University Jihlavska 20 625 00 Brno Czech Republic

Department of Pathophysiology Faculty of Medicine Masaryk University Kamenice 735 5 625 00 Brno Czech Republic

Department of Surgery Institution Shared with University Hospital Brno Faculty of Medicine Masaryk University Jihlavska 20 625 00 Brno Czech Republic

Institute of Biostatistics and Analyses Faculty of Medicine Masaryk University Kamenice 735 5 625 00 Brno Czech Republic

Institute of Microbiology of the Czech Academy of Sciences Videnska 1083 142 20 Prague Czech Republic

RECETOX Faculty of Science Masaryk University Kotlarska 2 602 00 Brno Czech Republic

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