Higher Methylation Levels in Gastric Mucosae Significantly Correlate with Higher Risk of Gastric Cancers

Nakajima, Takeshi; Maekita, Takao; Oda, Ichiro; Gotoda, Takuji; Yamamoto, Seiichiro; Umemura, Satoshi; Ichinose, Masakazu; Sügimura, Takashi; Saito, Daizo

doi:10.1158/1055-9965.epi-06-0436

Cited by 161 publications

(152 citation statements)

References 26 publications

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“…It is estimated that patients with severe gastric mucosal atrophy have high methylation levels because of long-term H. pylori infection and chronic inflammation. Additionally, we reported that patients with multiple gastric cancers had significantly higher methylation levels than those with a single gastric cancer [38]. These data indicate that severe gastric mucosal atrophy and multiple gastric cancers before successful H. pylori eradication are risk factors for MGC.…”

Section: Discussionmentioning

confidence: 57%

Incidence of and risk factors for metachronous gastric cancer after endoscopic resection and successful Helicobacter pylori eradication: results of a large-scale, multicenter cohort study in Japan

Mori

Nakajima

Asada³

et al. 2015

Gastric Cancer

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Background A previous multicenter prospective randomized study from Japan showed that Helicobacter pylori eradication reduced the development of metachronous gastric cancer (MGC) after endoscopic resection for early gastric cancer. MGC risk, however, is not eliminated; yet few studies have evaluated its long-term incidence and risk factors. In this study, we investigated the incidence of and risk factors for MGC in patients who underwent endoscopic resection for early gastric cancer with successful H. pylori eradication. Methods A total of 594 patients who underwent endoscopic resection for early gastric cancer and successful H. pylori eradication at three institutions (National Cancer Center Hospital, University of Tokyo Hospital, and Wakayama Medical University Hospital) were analyzed retrospectively. Annual endoscopic surveillance was performed after initial endoscopic resection. MGC was defined as a gastric cancer newly detected at least 1 year after successful H. pylori eradication. Results Ninety-four MGCs were detected in 79 patients during the 4.5-year median follow-up period. KaplanMeier analysis showed the cumulative incidence of MGC 5 years after successful H. pylori eradication was 15.0 %; the incidence of MGC calculated by use of the person-year method was 29.9 cases per 1000 person-years. Multivariate analysis using the Cox proportional hazards model revealed that male sex, severe gastric mucosal atrophy, and multiple gastric cancers before successful H. pylori eradication were independent risk factors for MGC. Eleven percent of MGCs (10 of 94) were detected more than 5 years after successful H. pylori eradication. Conclusion Surveillance endoscopy for MGC in patients who have undergone endoscopic resection for early gastric cancer should be performed even after successful H. pylori eradication.

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Section: Discussionmentioning

confidence: 57%

Incidence of and risk factors for metachronous gastric cancer after endoscopic resection and successful Helicobacter pylori eradication: results of a large-scale, multicenter cohort study in Japan

Mori

Nakajima

Asada³

et al. 2015

Gastric Cancer

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“…Previous studies have shown that H.pylori infection could induce aberrant DNA methylation at the CpG islands, resulting in inactivations of tumor suppressor genes in gastric mucosa, and creating predisposed fields for cancerization Nakajima et al, 2006;Tsang et al, 2011). In contrast, a study reported that H.pylori infection did not induce either mRNA or protein expression of DNMT1, DNMT3a and DNMT3B in gastric mucosa directly (Nakajima et al, 2009).…”

Section: Discussionmentioning

confidence: 93%

DNMT3a rs1550117 Polymorphism Association with Increased Risk of Helicobacter pylori Infection

Cao

Jia²,

Cao³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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“…Consequently, identification of sensitive and reliable biomarkers for diffuse type gastric cancer would be highly desirable. A number of studies have shown aberrant DNA methylation in precancerous lesions, including chronic gastritis and intestinal metaplasia, and detection of such an epigenetic field defect would provide useful information for identifying individuals at high risk for developing gastric cancer (7,24,25). The majority of those studies focused on well-studied genes, such as CDH1 and p16 (26,27), but recent advances in microarray technology have enabled us to conduct a genome-wide analysis of CpG island methylation status.…”

Section: Discussionmentioning

confidence: 99%

Aberrant Methylation of RASGRF1 Is Associated with an Epigenetic Field Defect and Increased Risk of Gastric Cancer

Takamaru

Yamamoto

Suzuki

et al. 2012

Cancer Prevention Research

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Aberrant DNA methylation is implicated in the epigenetic field defect seen in gastric cancer. Our aim in this study was to identify predictive biomarkers by screening for DNA methylation in noncancerous background gastric mucosa from patients with gastric cancer. Using methylated-CpG island amplification coupled with CpG island microarray (MCAM) analysis, we identified 224 genes that were methylated in the noncancerous gastric mucosa of patients with gastric cancer. Among them, RASGRF1 methylation was significantly elevated in gastric mucosa from patients with either intestinal or diffuse type gastric cancer, as compared with mucosa from healthy individuals (8.3% vs. 22.4%, P < 0.001; 8.3% vs. 19.4%, P < 0.001). RASGRF1 methylation was independent of mucosal atrophy and could be used to distinguish both serum pepsinogen test-positive [sensitivity, 70.0%; specificity, 86.7%; area under the receiver operator characteristic (ROC) curve, AUC, 0.763] and -negative patients with gastric cancer (sensitivity, 72.2%; specificity, 87.0%; AUC, 0.844) from healthy individuals. Ectopic expression of RASGRF1 suppressed colony formation and Matrigel invasion by gastric cancer cells, suggesting it may be involved in gastric tumorigenesis. Collectively, our data suggest that RASGRF1 methylation is significantly involved in an epigenetic field defect in the stomach, and that it could be a useful biomarker to identify individuals at high risk for gastric cancer. Cancer Prev Res; 5(10); 1203-12. Ó2012 AACR.

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Higher Methylation Levels in Gastric Mucosae Significantly Correlate with Higher Risk of Gastric Cancers

Cited by 161 publications

References 26 publications

Incidence of and risk factors for metachronous gastric cancer after endoscopic resection and successful Helicobacter pylori eradication: results of a large-scale, multicenter cohort study in Japan

Incidence of and risk factors for metachronous gastric cancer after endoscopic resection and successful Helicobacter pylori eradication: results of a large-scale, multicenter cohort study in Japan

DNMT3a rs1550117 Polymorphism Association with Increased Risk of Helicobacter pylori Infection

Aberrant Methylation of RASGRF1 Is Associated with an Epigenetic Field Defect and Increased Risk of Gastric Cancer

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