RT Journal Article
SR Electronic
T1 Demonstration of the usefulness of epigenetic cancer risk prediction by a multicentre prospective cohort study
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 388
OP 396
DO 10.1136/gutjnl-2014-307094
VO 64
IS 3
A1 Kiyoshi Asada
A1 Takeshi Nakajima
A1 Taichi Shimazu
A1 Nobutake Yamamichi
A1 Takao Maekita
A1 Chizu Yokoi
A1 Ichiro Oda
A1 Takayuki Ando
A1 Takeichi Yoshida
A1 Sohachi Nanjo
A1 Mitsuhiro Fujishiro
A1 Takuji Gotoda
A1 Masao Ichinose
A1 Toshikazu Ushijima
YR 2015
UL http://gut.bmj.com/content/64/3/388.abstract
AB 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.