Rs2274223 (A>G) is a non-synonymous single nucleotide polymorphism (SNP) located in 26th exon of the PLCE1 gene and result in the amino acid change from histidine (His) to arginine (Arg) at codon 1927 of PLCE1. In 2010, two large-scale genome-wide association studies (GWASs) simultaneously reported that the new and notable low-penetrance susceptibility locus rs2274223 was strongly associated with risk of esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA) in Chinese population [22], [23]. The gene discussed is PLCE1; the disease is gastric cardia adenocarcinoma.