Lack of association between EGF + 61A>G polymorphism and melanoma susceptibility in Caucasians: A HuGE review and meta-analysis

Emerging evidence showed that the common polymorphism (+ 61A>G, rs4444903) in the promoter region of epidermal growth factor (EGF) gene might be associated with melanoma susceptibility in humans. But individually published results are inconclusive. The aim of this Human Genome Epidemiology (HuGE) review and meta-analysis is to derive a more precise estimation of the association between EGF + 61A>G polymorphism and melanoma risk. The PubMed, Embase, Web of Science and CBM databases were searched for all articles published up to July 1st, 2012. Seven case-control studies were included with a total of 2367 melanoma cases and 4184 healthy controls. Meta-analysis results showed that there was no significant relationship between EGF + 61A>G polymorphism and the risk of melanoma (G vs A: odds ratio [OR] = 1.08, 95% confidence interval [CI]: 0.91-1.28, P = 0.386; GG + AG vs AA: OR = 1.05, 95%CI: 0.88-1.26, P = 0.580; GG vs AA + AG: OR = 1.10, 95%CI: 0.81-1.49, P = 0.552; GG vs AA: OR = 1.06, 95%CI: 0.80-1.41, P = 0.700; GG vs AG: OR = 1.12, 95%CI: 0.81-1.56, P = 0.494). Further subgroup analyses based on source of controls, country, detection samples, genotype methods, and Breslow thickness of tumor, we also found no significant association between EGF + 61A>G polymorphism and melanoma risk. In conclusion, this meta-analysis indicates that EGF + 61A>G polymorphism might not be a primary determinant in melanoma development and progression; EGF gene might be expected to interact with other genes in different signaling pathways to initiate and promote the carcinogenic process.

► A novel meta-analysis on the association of EGF + 61A>G with melanoma risk ► This meta-analysis has explained the role of EGF gene in melanoma risk. ► EGF + 61A>G polymorphism is not associated with melanoma susceptibility. ► This meta-analysis will be helpful in clarifying current controversies.