EGF +61A>G polymorphism and gastrointestinal cancer risk: a HuGE review and meta-analysis

Emerging evidences from preclinical and clinical studies have shown that epidermal growth factor (EGF) has some effectiveness against endogenously arising carcinogenesis. Functional +61A>G polymorphism (rs4444903 A>G) in the promoter region of the EGF gene was observed to modulate EGF levels, thus affecting the susceptibility to gastrointestinal cancer; but individually published studies showed inconclusive results. The aim of this Human Genome Epidemiology (HuGE) review and meta-analysis was to derive a more precise estimation of the association between EGF +61A>G polymorphism and gastrointestinal cancer risk. A literature search of Pubmed, Embase, Web of Science and Chinese BioMedical databases from inception through July 2012 was conducted. Twelve studies were assessed with a total of 2868 gastrointestinal cancer cases and 4278 healthy controls. When all the eligible studies were pooled into the meta-analysis, the results showed that the G allele and GG genotype of EGF +61A>G polymorphism might increase the risk of gastrointestinal cancer. In the stratified analysis by cancer types, the G allele and GG genotype of EGF +61A>G polymorphism showed displayed significant correlations with increased risk of esophageal cancer. We also found significant correlations between the G carrier (GG+AG) and GG genotype of EGF +61A>G polymorphism and colorectal cancer risk. However, EGF +61A>G polymorphism did not appear to have an influence on gastric cancer susceptibility. Results from the current meta-analysis indicate that EGF +61A>G polymorphism might increase the risk of esophageal and colorectal cancers. Nevertheless, further studies are needed to determine whether genetic associations between EGF +61A>G polymorphism and susceptibility to gastric cancer are significant.