Interaction of EGFR 497Arg>Lys with EGF +61A>G polymorphism: modulation of risk in esophageal cancer.

Genetic polymorphisms in EGFR 497Arg>Lys and EGF +61A>G genes influence cell cycle progression, apoptosis, angiogenesis, and metastasis. Therefore, we assessed association of esophageal cancer (EC), its clinical characteristics, and environmental interactions with these polymorphisms in 174 patients with EC and 196 controls. No association of EGFR 497Arg/Arg genotype was observed (OR 1.48, p = 0.067) but EGF +61A/A genotype was significantly associated with risk of EC (OR 1.65, p = 0.025), particularly in males (OR 1.76, p = 0.031). Patients with EGF +61A/A genotype were at risk for squamous cell carcinoma (SCC) (OR 1.70, p = 0.021) and tumor at upper anatomical location (OR 3.11, p = 0.009). Interaction of EGF or EGFR genotypes with environmental exposure did not modulate EC risk. However, in gene-gene interaction, EGFR 497Arg/Arg*EGF +61A/A showed significant risk for EC (OR 2.47, p = 0.011). In conclusion, EGF +61A>G gene polymorphisms influenced EC susceptibility and its clinical characteristics. Gene-gene interaction of EGFR 497Arg>Lys and EGF +61A>G polymorphisms enhanced risk for EC, indicating additive effects.