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

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.

SUBMITTER: Asada K

PROVIDER: S-EPMC4345890 | biostudies-other | 2015 Mar

REPOSITORIES: biostudies-other

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

Asada Kiyoshi K Nakajima Takeshi T Shimazu Taichi T Yamamichi Nobutake N Maekita Takao T Yokoi Chizu C Oda Ichiro I Ando Takayuki T Yoshida Takeichi T Nanjo Sohachi S Fujishiro Mitsuhiro M Gotoda Takuji T Ichinose Masao M Ushijima Toshikazu T

Gut 20140602 3

<h4>Background</h4>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.<h4>Objective</h4>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 ...[more]

PMID: 25379950

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

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

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