Demonstration of the usefulness of epigenetic cancer risk prediction by a multicentre prospective cohort study. Issue 3 (2nd June 2014)

• Record Type: Journal Article
• Authors: Asada, Kiyoshi; Nakajima, Takeshi; Shimazu, Taichi; Yamamichi, Nobutake; Maekita, Takao; Yokoi, Chizu; Oda, Ichiro; Ando, Takayuki; Yoshida, Takeichi; Nanjo, Sohachi; Fujishiro, Mitsuhiro; Gotoda, Takuji; Ichinose, Masao; Ushijima, Toshikazu
• Other Names: Yoshinaga Shigetaka author non-byline.; Suzuki Haruhisa author non-byline.
• Is Part Of: Gut. Volume 64:Issue 3(2015)
• Page Start: 388
• Page End: 396
• Publication Date: 2014-06-02
• Subjects: GASTRIC CANCER -- METHYLATION; Gastroenterology -- Periodicals; 616.33
• DOI: 10.1136/gutjnl-2014-307094
• Languages: English
• ISSNs: 0017-5749

Abstract

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.