Helicobacter pylori infection is an independent risk factor for Runx3 methylation in gastric cancer

Abstract

Runx3, a member of the human runt-related transcription factor family, is known as a possible tumor suppressor gene for gastric cancer. Runx 3 expression is frequently suppressed by the promoter hypermethylation in gastric cancer cell lines and tissues. However, the precise mechanism of the induction of Runx3 methylation, which is considered to be a critical step in gastric carcinogenesis, remains to be elucidated. In the present study, we evaluated runx3 gene methylation in 57 resected early gastric cancer specimens. Then, we correlated Runx3 methylation in the cancer tissue specimens with clinicopathological factors as well as the mucosal backgrounds, such as intestinal metaplasia surrounding the cancer cells and Helicobacter pylori (H. pylori) infection. Runx3 methylation was observed in 30 of the 57 (52.6%) cancer specimens, whereas methylation was detected in 10 of the 57 (17.5%) corresponding noncancerous mucosae. In comparison to the clinicopathological factors, Runx3 methylation was significantly correlated with both age and tumor location. A multivariate analysis demonstrated that age and tumor location as well as H. pylori infection were independent risk factors for Runx3 methylation. We demonstrated for the first time that H. pylori infection contributes to Runx3 methylation in gastric cancer tissues. When a persistent infection by H. pylori continues in the middle/lower stomach for a long period, Runx3 methylation may be induced and the subsequent loss of Runx3 expression may therefore affect gastric carcinogenesis.

Stepwise cumulation of RUNX3 methylation mediated by Helicobacter pylori infection contributes to gastric carcinoma progression

“…(B) The survival rate was significantly lower for patients who had higher serum methylation scores compared with patients who had lower serum methylation scores (P < .0001). between H. pylori infection and RUNX3 promoter methylation in GC initially was reported in 2008 by Kitajima et al 48 Furthermore, there is a significant correlation between H. pylori infection and RUNX3 methylation not only in GC cells but also in precancerous gastric lesions like chronic atrophy gastritis, intestinal metaplasia, and dysplasia. 24 Compared with previous studies, we report a much more significant correlation between H. pylori infection and RUNX3 promoter methylation.…”

Prospects for Epigenetic Epidemiology

“…Aberrant methylation of gastric mucosa genes is a common finding in humans infected with Helicobacter pylori and is an early event in gastric carcinogenesis (143)(144)(145). Insulin-like growth factor 2 methylation imprinting profile in the placenta is altered in mice infected with Campylobacter rectus during pregnancy (142).…”

RUNX3Methylation, Loss of RUNX3 Expression and Clinicopathologic Findings according toHelicobacter pyloriCagA in Gastric Carcinoma

“…H. pylori 16S RNA may be an independent risk factor for RUNX3 methylation in patients with early gastric carcinoma. 11 The protein mislocalization of RUNX3, because of which it moves from the nucleus to the cytoplasm, may be a major mechanism underlying the association between H. pylori infection and gastric carcinoma development. 9 RUNX3 inactivation occurs early during the progression to malignancy.…”