Wenzhen Xie1, Haibo Zhou1, Qian Han1, Tong Sun1, Chuang Nie1, Jia Hong1, Rongrong Wei1, Anastasiia Leonteva1, Xu Han1, Jing Wang1, Xinyu Du1, Lin Zhu1, Yashuang Zhao1, Wenjing Tian2, Yingwei Xue3. 1. Department of Epidemiology, College of Public Health, Harbin Medical University, 197 Xuefu Road, Harbin, 150081, Heilongjiang, People's Republic of China. 2. Department of Epidemiology, College of Public Health, Harbin Medical University, 197 Xuefu Road, Harbin, 150081, Heilongjiang, People's Republic of China. twj8267@sina.com. 3. Department of Gastroenterological Surgery, Harbin Medical University Cancer Hospital, 150 Haping Road, Harbin, 150081, Heilongjiang, People's Republic of China. xueyingwei@hrbmu.edu.cn.
Abstract
PURPOSE: Aberrant DNA methylation could regulate the expression of tumor suppressor gene DLEC1 and oncogene PBX3 and was related to the occurrence and prognosis of gastric cancer (GC). In this study, the associations between DLEC1 and PBX3 promoter methylation in peripheral blood leukocytes (PBLs) and the risk and prognosis of GC were investigated. METHODS: The methylation status of DLEC1 and PBX3 promoter in PBLs of 368 GC cases and 382 controls was detected by the methylation-sensitive high-resolution melting (MS-HRM) method. Logistic and Cox regression were adopted to analyze the associations of DLEC1 and PBX3 methylation with GC risk and prognosis, respectively. Confounding biases were controlled by propensity score (PS). RESULTS: Compared with negative methylation (Nm), DLEC1-positive methylation (Pm) was associated with increased GC risk in PS (OR 2.083, 95% CI 1.220-3.558, P = 0.007), but PBX3 Pm was not associated with GC risk. In the elderly group (≥ 60 years), DLEC1 Pm was associated with increased GC risk (OR 2.951, 95% CI 1.426-6.104, P = 0.004). The combined effects between DLEC1 methylation and consumption of dairy products, fried food intake and Helicobacter pylori (H. pylori) infection on GC risk were discovered (ORc 3.461, 95% CI 1.847-6.486, P < 0.001, ORc 3.246, 95% CI 1.708-6.170, P < 0.001 and ORc 2.964, 95% CI 1.690-5.197, P < 0.001, respectively). Furthermore, DLEC1 and PBX3 methylation were not associated with GC prognosis. CONCLUSION: DLEC1 methylation in PBLs and the combined effects of gene-environment can influence GC risk.
PURPOSE: Aberrant DNA methylation could regulate the expression of tumor suppressor gene DLEC1 and oncogene PBX3 and was related to the occurrence and prognosis of gastric cancer (GC). In this study, the associations between DLEC1 and PBX3 promoter methylation in peripheral blood leukocytes (PBLs) and the risk and prognosis of GC were investigated. METHODS: The methylation status of DLEC1 and PBX3 promoter in PBLs of 368 GC cases and 382 controls was detected by the methylation-sensitive high-resolution melting (MS-HRM) method. Logistic and Cox regression were adopted to analyze the associations of DLEC1 and PBX3 methylation with GC risk and prognosis, respectively. Confounding biases were controlled by propensity score (PS). RESULTS: Compared with negative methylation (Nm), DLEC1-positive methylation (Pm) was associated with increased GC risk in PS (OR 2.083, 95% CI 1.220-3.558, P = 0.007), but PBX3 Pm was not associated with GC risk. In the elderly group (≥ 60 years), DLEC1 Pm was associated with increased GC risk (OR 2.951, 95% CI 1.426-6.104, P = 0.004). The combined effects between DLEC1 methylation and consumption of dairy products, fried food intake and Helicobacter pylori (H. pylori) infection on GC risk were discovered (ORc 3.461, 95% CI 1.847-6.486, P < 0.001, ORc 3.246, 95% CI 1.708-6.170, P < 0.001 and ORc 2.964, 95% CI 1.690-5.197, P < 0.001, respectively). Furthermore, DLEC1 and PBX3 methylation were not associated with GC prognosis. CONCLUSION: DLEC1 methylation in PBLs and the combined effects of gene-environment can influence GC risk.
Entities:
Keywords:
DNA methylation; Gastric cancer; Peripheral blood leukocytes; Propensity score
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