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.
journal_name
Gutjournal_title
Gutauthors
Asada K,Nakajima T,Shimazu T,Yamamichi N,Maekita T,Yokoi C,Oda I,Ando T,Yoshida T,Nanjo S,Fujishiro M,Gotoda T,Ichinose M,Ushijima Tdoi
10.1136/gutjnl-2014-307094subject
Has Abstractpub_date
2015-03-01 00:00:00pages
388-96issue
3eissn
0017-5749issn
1468-3288pii
gutjnl-2014-307094journal_volume
64pub_type
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