In cellular mechanisms, ERK appears to be involved in a wide variety of cellular processes. Thus, the host gene of ERK protein may be more important in determining protein expression and capacity. The results of this study demonstrate that ERK rs5999749 is primarily selected in SNP-based analysis and retains its strong association with gastric cancer in the final combined analyses. This supports that its genetic effect can play a critical role in gastric carcinogenesis equal to its protein activity level at the cellular stage. Dock180,Rapamycin synonymous with a dedicator of cytokinesis 1, is a 180 kDa protein downstream-combining molecule of Crk and up-regulator of Rac1. It modulates various functions, including cell spreading, cell migration, and actin cytoskeletal organization through activation of Rac1. This protein is one of the Crk-downstream proteins involved in the cascade of CagA and Crk signaling through the Crk-Codk180-ELMo pathway. Similarly,SAR131675 C3G known as Rap guanine nucleotide exchange factor 1 also interacts with the Crk. Previous studies demonstrated that the Crk-C3G-Rap1 signaling can activate the ERK cascade and induce apoptosis, cell growth, migration, adhesion and mortality. In human carcinogenesis, the C3G gene appears to play a crucial role by itself. Alteration of the C3G genetic activity via amplification or methylation is associated with several cancers such as lung, gastrointestinal and gynecological cancers. Although it is not exactly well known whether the genetic variants of the Dock 180 and C3G gene are linked to gastric carcinogenesis, our study suggests several SNPs in these genes, especially rs4635002 and rs7853122, are significantly associated with risk of gastric cancer, and thus may be a susceptible gene in the development of gastric cancer. Based on the present results and review of cellular mechanisms, CagA oncogenicity induced by activation of the ERK signal pathway can be infered. The CagA interaction with binding molecules such as Src, Crk, GRB2 and SHP-2 stimulates the downstream signals in the ERK cascade linked to aberrant cellular functions that leads to gastric carcinogenesis. During this process, the genetic effects of ERK, Dock180 and C3G can play critical roles equal to their protein activities.