Functional epidermal growth factor gene polymorphisms and risk of gastric cancer

Epidermal growth factor (EGF) is critical in cancer progression and various genotypes of the EGF gene have been reported to be correlated with susceptibility to gastric cancer; however, the results are unclear. The aim of this study was to explore the associations of functional EGF gene polymorphisms and risk of gastric cancer in a Chinese population. We genotyped seven functional single-nucleotide polymorphisms (SNPs) of the EGF gene [rs3756261, rs11568835 and rs4444903 in the promoter region; rs11568943, rs2237051 and rs11569017 in the non-synonymous exon region and rs3733625 in the 3′ untranslated region (UTR)] in a hospital-based case-control study, including 387 gastric cancer cases and 392 healthy controls by polymerase chain reaction-ligation detection reaction (PCR-LDR) methods. We found that individuals carrying the AG/GG genotype of rs2237051 (Ile to Met) in the exon region had an increased risk of gastric cancer (adjusted OR=1.577; 95% CI=1.163–2.138), compared with the wild-type homozygous AA genotype. The heterozygous AG/GG genotype of rs3733625 in the 3′UTR demonstrated a protective effect (adjusted OR=0.690; 95% CI=0.501–0.951), compared with the homozygous AA genotype. In addition, the effects of the two SNPs were more evident in intestinal gastric cancer (P<0.05); however, this was not case for the diffuse type (P>0.05). These findings indicate that a change in amino acids from isoleucine to methionine of rs2237051 and rs3733625 in the 3′UTR may contribute to the etiology of intestinal gastric cancer in the Chinese population.