IL10 hypomethylation is associated with the risk of gastric cancer.

Interleukin-10 (IL10), a pleiotropic cytokine secreted by type-2 helper (Th2) T cells, contributes to the oncogenic activation or inactivation of tumor-suppressor genes. The present study investigated whether hypomethylation of CpG island (CGI) was associated with the risk of developing gastric cancer (GC) and the prognosis of patients with GC. A fragment (hg18, chr1: 206945638-206945774) at the CGI of IL10 was selected for the present methylation assay. Quantitative methylation-specific PCR was used to evaluate the methylation of CGI in 117 tumor samples from patients with GC. The results demonstrated that CGI methylation was significantly lower in the tumor tissues compared with that in the paired adjacent non-tumor tissues (median percentage of methylated reference, 29.16 vs. 42.82%, respectively; P=4×10). Furthermore, results from receiver operating characteristic curve analysis identified a significant area under the curve of 0.706, with a sensitivity and a specificity of 77.8 and 58.1%, respectively, between cancer tissues and paired adjacent non-tumor tissues. Furthermore, the methylation of CGI was significantly associated with patients' age at diagnosis (r=-0.201; P=0.03). Subgroup analyses demonstrated that the association between CGI hypomethylation and the risk of GC was specific for patients with low differentiation (P=1×10) and Borrmann types III+IV (P=1×10). In addition, CGI hypomethylation was significantly associated with the risk of GC for patients without smoking history (P=3×10) or a family history of cancer (P=2×10). The results from Kaplan-Meier survival analysis demonstrated that CGI hypomethylation was associated with a significantly shorter overall survival of patients with GC (P=0.041). Similar results were identified for patients with GC who did not have smoking history (P=0.037) or a family history of cancer (P=0.049). The results from this study demonstrated that CGI hypomethylation may be considered as a potential biomarker for the diagnosis and prognosis of patients with GC in the Chinese population.