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Background:Single-nucleotide polymorphisms of key cancer genes, such asEGF A61G, are associated with an elevated risk of esophageal adenocarcinoma (EAC). As gastroesophageal reflux disease (GERD) is an established risk factor for EAC, we evaluated whether the association between epidermal growth factor (EGF) polymorphism and EAC development is altered by the presence of GERD.Methods:  EGFgenotyping of DNA samples was performed and GERD history was collected for 309 EAC patients and 275 matched healthy controls. Associations between genotypes and EAC risk were evaluated using adjusted logistic regression. Genotype–GERD relationships were explored using analyses stratified by GERD history and joint effects models that considered severity and duration of GERD symptoms.Results:  EGFvariants (A/GorG/G) were more common (P = 0.02) and GERD was more prevalent (P&lt; 0.001) in cases than in controls. When compared with theEGFwild-typeA/Agenotype, theG/Gvariant was associated with a substantial increase in EAC risk among individuals with GERD [Odds ratio 9.7; 95% confidence interval (CI), 3.8–25.0;P &lt; 0.001] and a slight decrease in risk for GERD-free individuals (odds ratio 0.4; 95% CI = 0.22–0.90;P = 0.02). In the joint effects models, the odds of EAC was also highest forG/Gpatients (when compared withA/A) who either experienced frequent GERD of more than once per week (odds ratio 21.8; 95% CI = 5.1–94.0;P &lt; 0.001) or suffered GERD for longer than 15 years (odds ratio 22.4; 95% CI = 6.5–77.6;P &lt; 0.001). There was a highly significant interaction between theG/Ggenotype and the presence of GERD (P &lt; 0.001).Conclusions:  EGF A61Gpolymorphism may alter EAC susceptibility through an interaction with GERD.

Epidermal growth factor A61G gene polymorphism, gastroesophageal reflux disease and esophageal adenocarcinoma risk