E-Selectin rs5361 and FCGR2A rs1801274 variants were associated with increased risk of gastric cancer in a Chinese population
Xia, H-Z and Du, W-D and Wu, Q and Chen, G and Zhou, Y and Tang, X-F and Tang, H-Y and Liu, Y and Yang, F and Ruan, J and Xu, S and Zuo, X-B and Zhang, X-J, E-Selectin rs5361 and FCGR2A rs1801274 variants were associated with increased risk of gastric cancer in a Chinese population, Molecular Carcinogenesis, 51, (8) pp. 597-607. ISSN 0899-1987 (2012) [Refereed Article]
Host immune responses are critical steps for carcinogenesis. Single nucleotide polymorphisms (SNPs) in immunoregulatory genes may influence gastric cancer risk. We performed a genotyping analysis for immunoregulatory genes in 311 gastric cancer cases and 425 controls from a Chinese population. We found that there were significant differences of E-selectin variant rs5361 (A>C) and FCGR2A variant rs1801274 (T>C) between cases and controls (P = 0.022 and P = 0.0001, respectively). Logistic regression analysis indicated that genotype of E-selectin rs5361AC increased the risk of gastric cancer significantly (P = 0.026, adjusted Odds ratio (OR) = 2.84, 95% confidence interval (CI) = 1.13-7.12). C allele of E-selectin rs5361 showed a significant increased frequency in cases (P = 0.023). However, the E-selectin variant did not affect the protein expression. E-selectin protein was observed not only in tumor interstitial vascular endothelial cells, but also in gastric cancer cells at primary and metastatic sites. The protein was associated with clinicopathological characteristics of gastric cancer, such as age (P = 0.008), tumor size (P = 0.027), differentiation (P = 0.000), and tumor-node-metastasis (TNM) stage (P = 0.006). CT and CC + CT genotypes of FCGR2A variant rs1801274 increased gastric cancer risk (P = 0.000, adjusted OR = 1.92, 95%CI = 1.36-2.72; P = 0.003, adjusted OR = 1.68, 95%CI = 1.20-2.35, respectively). Interleukin-4 receptor (IL-4R) variant rs2107356 presented negative correlations to E-selectin variant rs5361 and FCGR2A variant rs1801274 (P = 0.035 and P = 0.023) in conferring susceptibility to gastric cancer. We concluded E-selectin variant rs5361 and FCGR2A variant rs1801274 were significantly associated with gastric cancer risk. Expression of E-selectin protein would promote progression of gastric cancer.