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Gut. 2015 Mar;64(3):388-96. doi: 10.1136/gutjnl-2014-307094. Epub 2014 Jun 2.

Demonstration of the usefulness of epigenetic cancer risk prediction by a multicentre prospective cohort study.

Author information

1
Division of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan.
2
Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan.
3
Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan.
4
Department of Gastroenterology, University of Tokyo, Tokyo, Japan.
5
Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan.
6
Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan Department of Gastroenterology and Hepatology, National Center for Global Health and Medicine, Tokyo, Japan.
7
Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan.

Abstract

BACKGROUND:

Epigenetic alterations accumulate in normal-appearing tissues of patients with cancer, producing an epigenetic field defect. Cross-sectional studies show that the degree of the defect may be associated with risk in some types of cancer, especially cancers associated with chronic inflammation.

OBJECTIVE:

To demonstrate, by a multicentre prospective cohort study, that the risk of metachronous gastric cancer after endoscopic resection (ER) can be predicted by assessment of the epigenetic field defect using methylation levels.

DESIGN:

Patients with early gastric cancer, aged 40-80 years, who planned to have, or had undergone, ER, were enrolled at least 6 months after Helicobacter pylori infection discontinued. Methylation levels of three preselected genes (miR-124a-3, EMX1 and NKX6-1) were measured by quantitative methylation-specific PCR. Patients were followed up annually by endoscopy, and the primary endpoint was defined as detection of a metachronous gastric cancer. Authentic metachronous gastric cancers were defined as cancers excluding those detected within 1 year after the enrolment.

RESULTS:

Among 826 patients enrolled, 782 patients had at least one follow-up, with a median follow-up of 2.97 years. Authentic metachronous gastric cancers developed in 66 patients: 29, 16 and 21 patients at 1-2, 2-3 and ≥3 years after the enrolment, respectively. The highest quartile of the miR-124a-3 methylation level had a significant univariate HR (95% CI) (2.17 (1.07 to 4.41); p=0.032) and a multivariate-adjusted HR (2.30 (1.03 to 5.10); p=0.042) of developing authentic metachronous gastric cancers. Similar trends were seen for EMX1 and NKX6-1.

CONCLUSIONS:

Assessment of the degree of an epigenetic field defect is a promising cancer risk marker that takes account of life history.

KEYWORDS:

GASTRIC CANCER; METHYLATION

PMID:
25379950
PMCID:
PMC4345890
DOI:
10.1136/gutjnl-2014-307094
[Indexed for MEDLINE]
Free PMC Article

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