Role of the EGF +61A>G polymorphism in melanoma pathogenesis: an experience on a large series of Italian cases and controls

Individuals with less than 10 (N = 127) or more than 100 (N = 128) benign nevi, and patients with cutaneous melanoma (N = 418) were investigated for the EGF +61A>G polymorphism, using an automated sequencing approach.Overall, no difference in EGF genotype frequencies was observed among subjects with different number of nevi as well as when non-melanoma healthy controls were compared with the melanoma patients. However, a heterogeneous distribution of the frequencies of the G/G genotype was detected among cases and controls originating from North Italy (21.1 and 18.3%, respectively) vs. those from South Italy (12.6 and 17.1%, respectively).Our findings further suggest that EGF +61A>G polymorphism may have a limited impact on predisposition and/or pathogenesis of melanoma and its prevalence may vary in different populations.The epidermal growth factor (EGF) gene, which is a member of the EGF superfamily, has been demonstrated to activate cell proliferation and stimulate mitogenesis in epidermal tissue, enhancing tumour growth [1].In a previous case-control study conducted in the United Kingdom, the 61A>G transversion (rs4444903) in the EGF gene has been correlated with an increased risk of melanoma in vivo [2]. In particular, the prevalence of the G/G genotype was significantly higher in melanoma patients than in healthy individuals as controls (both originating from northern European countries); the G allele was present in nearly 66% of patients with malignant melanoma (odds ratio 4.9 [95% CI 2.3–10.2]; p < 0.0001) [2]. Overall, the A and G alleles have been reported in 56–63% and 37–44%, respectively, of all the EGF alleles in the European Caucasian populations [2-8]. Among melanoma patients, a significant association with the Breslow thickness was also inferred (odds ratio 3.7 [95% CI 1.0–13.2]; p = 0.045) [2].From the biological point of view, it has been hypothesized that presence of the G allele at position 61 of the EGF gene leads to increased in vitro expressi