BACKGROUND: Peripheral blood leukocyte DNA methylation status has been proposed to be a surrogate marker for evaluating susceptibility to gastric cancer (GC). Helicobacter pylori (H pylori) infection, smoking, and alcohol consumption are known to induce gene methylation. A case-control study was performed to investigate the interactions between the methylation of two candidate genes and H pylori infection, smoking, and alcohol consumption in the risk of GC. METHODS: A total of 400 GC cases and 402 controls were included in this study. The methylation status of WT1 and IGF2 was semiquantitatively determined by using methylation-sensitive high-resolution melting assays. H pylori IgG antibodies were detected by ELISA method. RESULTS: Based on the area under the curve (AUC), 0% methylated DNA and 0.5% methylated DNA were used as the cutoff values for WT1 and IGF2, respectively. WT1 methylation was significantly associated with increased GC risk (OR = 1.65, 95% CI = 1.09-2.51, P = .019), especially in males (OR = 1.80, 95% CI: 1.10-2.95, P = .019) and older individuals (≥60 years) (OR = 2.03, 95% CI: 1.15-3.57, P = .014). A significant combination was observed between WT1 methylation and H pylori infection, alcohol consumption, and smoking for the risk of GC (ORc = 2.28, 95% CI = 1.47-3.55, P = .003, ORc = 2.19, 95% CI = 1.37-3.51, P = .001, ORc = 2.21, 95% CI = 1.39-3.51, P = .001, respectively). However, no association between IGF2 methylation and the risk of GC was found in this study. CONCLUSIONS: WT1 methylation may serve as a new potential biomarker for GC susceptibility and can combine with H pylori infection, smoking, and alcohol consumption to influence GC risk.
BACKGROUND: Peripheral blood leukocyte DNA methylation status has been proposed to be a surrogate marker for evaluating susceptibility to gastric cancer (GC). Helicobacter pylori (H pylori) infection, smoking, and alcohol consumption are known to induce gene methylation. A case-control study was performed to investigate the interactions between the methylation of two candidate genes and H pylori infection, smoking, and alcohol consumption in the risk of GC. METHODS: A total of 400 GC cases and 402 controls were included in this study. The methylation status of WT1 and IGF2 was semiquantitatively determined by using methylation-sensitive high-resolution melting assays. H pylori IgG antibodies were detected by ELISA method. RESULTS: Based on the area under the curve (AUC), 0% methylated DNA and 0.5% methylated DNA were used as the cutoff values for WT1 and IGF2, respectively. WT1 methylation was significantly associated with increased GC risk (OR = 1.65, 95% CI = 1.09-2.51, P = .019), especially in males (OR = 1.80, 95% CI: 1.10-2.95, P = .019) and older individuals (≥60 years) (OR = 2.03, 95% CI: 1.15-3.57, P = .014). A significant combination was observed between WT1 methylation and H pylori infection, alcohol consumption, and smoking for the risk of GC (ORc = 2.28, 95% CI = 1.47-3.55, P = .003, ORc = 2.19, 95% CI = 1.37-3.51, P = .001, ORc = 2.21, 95% CI = 1.39-3.51, P = .001, respectively). However, no association between IGF2 methylation and the risk of GC was found in this study. CONCLUSIONS: WT1 methylation may serve as a new potential biomarker for GC susceptibility and can combine with H pylori infection, smoking, and alcohol consumption to influence GC risk.