Lack of Association between Epidermal Growth Factor or Its Receptor and Reflux Esophagitis, Barrett's Esophagus, and Esophageal Adenocarcinoma: A Case-Control Study.
Tereza Deissova, Michaela Cvanova, Zdenek Kala, Zuzana Jiraskova Zakostelska, Jiri Dolina, Lumir Kunovsky, Radek Kroupa, Zdenek Pavlovsky, Bretislav Lipovy, Zdenek Danek, Lydie Izakovicova Holla, Ondrej Urban, Vit Navratil, Robert Lischke, Tomas Harustiak, Tomas Grolich, Vladimir Prochazka, Ondrej Slaby, Petra Borilova Linhartova
Zdenek Kala: Department of Surgery, Institution Shared with University Hospital Brno, Faculty of Medicine, Masaryk University, Jihlavska 20, 625 00 Brno, Czech Republic.
Zuzana Jiraskova Zakostelska: Institute of Microbiology of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech Republic.
Jiri Dolina: Department of Gastroenterology and Internal Medicine, Institution Shared with University Hospital Brno, Faculty of Medicine, Masaryk University, Jihlavska 20, 625 00 Brno, Czech Republic.
Lumir Kunovsky: Department of Surgery, Institution Shared with University Hospital Brno, Faculty of Medicine, Masaryk University, Jihlavska 20, 625 00 Brno, Czech Republic.
Radek Kroupa: Department of Gastroenterology and Internal Medicine, Institution Shared with University Hospital Brno, Faculty of Medicine, Masaryk University, Jihlavska 20, 625 00 Brno, Czech Republic.
Zdenek Pavlovsky: Department of Pathology, Institution Shared with University Hospital Brno, Faculty of Medicine, Masaryk University, Jihlavska 20, 625 00 Brno, Czech Republic.
Bretislav Lipovy: Department of Burns and Plastic Surgery, Institution Shared with University Hospital Brno, Faculty of Medicine, Masaryk University, Jihlavska 20, 625 00 Brno, Czech Republic.
Lydie Izakovicova Holla: Department of Pathophysiology, Faculty of Medicine, Masaryk University, Kamenice 735/5, 625 00 Brno, Czech Republic.
Ondrej Urban: 2nd Department of Internal Medicine - Gastroenterology and Geriatrics, University Hospital Olomouc, Faculty of Medicine and Dentistry, Palacky University, I. P. Pavlova 6, 779 00 Olomouc, Czech Republic.
Vit Navratil: 2nd Department of Internal Medicine - Gastroenterology and Geriatrics, University Hospital Olomouc, Faculty of Medicine and Dentistry, Palacky University, I. P. Pavlova 6, 779 00 Olomouc, Czech Republic.
Robert Lischke: 3rd Department of Surgery, First Faculty of Medicine, Charles University and Motol University Hospital, V Uvalu 84, 150 06 Prague, Czech Republic.
Tomas Harustiak: 3rd Department of Surgery, First Faculty of Medicine, Charles University and Motol University Hospital, V Uvalu 84, 150 06 Prague, Czech Republic.
Tomas Grolich: Department of Surgery, Institution Shared with University Hospital Brno, Faculty of Medicine, Masaryk University, Jihlavska 20, 625 00 Brno, Czech Republic.
Vladimir Prochazka: Department of Surgery, Institution Shared with University Hospital Brno, Faculty of Medicine, Masaryk University, Jihlavska 20, 625 00 Brno, Czech Republic.
Ondrej Slaby: Central European Institute of Technology, Masaryk University, Kamenice 735/5, 625 00 Brno, Czech Republic.
Petra Borilova Linhartova: RECETOX, Faculty of Science, Masaryk University, Kotlarska 2, 602 00 Brno, Czech Republic. ORCID
The epidermal growth factor () and its receptor () 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 and 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 (rs4444903) and +142285 G>A (rs2227983) polymorphisms using the TaqMan quantitative polymerase chain reaction (qPCR). In random subgroups, the and 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 genotype interactions were associated with RE, BE, or EAC development ( > 0.05). Moreover, mRNA expression of neither nor differed between samples of the esophageal tissue with and without endoscopically visible pathology ( > 0.05) nor between samples from patients with different diagnoses, i.e., RE, BE, or EAC ( > 0.05). Nevertheless, the lower mRNA expression in carriers of combined genotypes AA +61 (rs4444903) and GG +142285 (rs2227983; < 0.05) suggests a possible direct/indirect effect of - gene interactions on gene expression. In conclusion, and gene variants and their mRNA/protein expression were not associated with RE, BE or EAC development in the Central European population.
