Lack of Association between Epidermal Growth Factor or Its Receptor and Reflux Esophagitis, Barrett's Esophagus, and Esophageal Adenocarcinoma: A Case-Control Study.

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.