Abstract
The silencing of the tumor suppressor gene O-6-methylguanine-DNA methyltransferase (MGMT) by promoter methylation commonly occurs in human cancers. The relationship between MGMT promoter methylation and gastric cancer (GC) remains inconsistent. This study aimed to evaluate the potential value of MGMT promoter methylation in GC patients. Electronic databases were searched to identify eligible studies. The pooled odds ratio (OR) and the corresponding 95% confidence interval (95% CI) were used to evaluate the effects of MGMT methylation on GC risk and clinicopathological characteristics. In total, 31 eligible studies including 2988 GC patients and 2189 nonmalignant controls were involved in meta-analysis. In the pooled analysis, MGMT promoter methylation was significantly associated with GC risk (OR = 3.34, P < 0.001) and substantial heterogeneity (P < 0.001). Meta-regression and subgroup analyses based on the testing method, sample material and ethnicity failed to explain the sources of heterogeneity. Interestingly, MGMT methylation showed a trend associated with gender, and methylation is lower in males compared with females (OR = 0.76, 95% CI = 0.56–1.03). We did not find a significant association in relation to tumor types, clinical stage, age status or H. pylori status in cancer (all P > 0.1). MGMT promoter methylation may be correlated with the prognosis of GCs in disease free survival (DFS) or overall survival (OS) for univariate analysis. MGMT promoter methylation may play a crucial role in the carcinogenesis and prognosis of GC. MGMT methylation was not correlated with tumor types, clinical stage, age status, H. pylori status. However, the result of the association of MGMT methylation and gender should be considered with caution.
Highlights
As one of the most common malignant diseases, gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide
20 studies reporting 2120 cases and 2189 nonmalignant controls were calculated to assess the association between methylguanine-DNA methyltransferase (MGMT) methylation and GC risk, and 17 studies reporting 1299 male GC patients and 775 female GC patients were used to evaluate the association between MGMT methylation and gender
11 studies, including 464 patients with intestinal gastric cancer and 416 patients with diffuse gastric cancer, evaluated the association between MGMT methylation and tumor type; 10 studies including 221 stage 1–2 patients and 469 stage 3–4 patients evaluated the association between MGMT methylation and tumor stage; 9 studies assessed the correlation between MGMT promoter methylation and age status; and 3 studies involving 139 H. pylori-positive patients and 147 H. pylori-negative patients explored the association between MGMT methylation and H. pylori infection status. 2 studies with 198 GC patients reported survival
Summary
As one of the most common malignant diseases, gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide. MGMT Promoter Methylation and Gastric Cancer deaths worldwide [1]. Helicobacter pylori (H. pylori) infection affects more than 50% of the adult population in the world and accounts for 75% of all gastric cancer cases [2]. H. pylori infection is a strong risk factor for GC, increasing the risk of developing gastric cancer. GC is divided into two main histological subtypes based on Lauren’s classification: intestinal and diffuse-type gastric cancer [3]. For both types, a strong association with H. pylori-correlated inflammation exists [4]
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