Abstract LB-092: High impact of methylation accumulation on cancer risk: 5-year follow-up of a multicenter prospective cohort study

Abstract

Abstract Aberrant DNA methylation can be accumulated in normal-appearing tissues, and its degree can be correlated with cancer risk [Hattori, Genome Med, 8:10, 2016]. Such accumulation is especially prominent in inflammation-associated cancers, including gastric cancer. To bring the findings into cancer risk diagnosis, we conducted a multicenter prospective cohort study with 826 patients [Asada, Gut, 64:388, 2015]. Between 2008 and 2010, 826 patients after endoscopic treatment of gastric cancer and without current H. pylori infection were enrolled, and a gastric biopsy was collected. Methylation levels of pre-defined three marker genes (miR-124a-3, EMX1 and NKX6-1) were measured by quantitative methylation-specific PCR. Patients were classified into quartiles according to methylation levels of individual genes (Q1, the lowest; Q4, the highest). Among the 826 enrolled patients, 795 patients received annual follow-ups by endoscopy with a median period of 5.46 years (interquartile range: 3.95 - 6.09). By the end, 133 patients developed a metachronous gastric cancer, and 116 of them developed a cancer after 1 year of the enrollment (authentic metachronous cancer). Kaplan-Meier analysis showed that Q4 had a higher cumulative incidence of metachronous gastric cancer than Q1 with p-values of <0.001 to 0.004 (log-rank test). Multivariate analyses adjusted for hospital, gender and age, pepsinogen index, history of endoscopic treatment, smoking and green vegetable intake also showed that Q4 had significantly high HRs compared with Q1, being 3.0 (95%CI: 1.58 to 5.72, p=0.0017) for miR-124a-3 [Maeda, Gut, online]. The results clearly showed that accumulation levels of aberrant DNA methylation can be used for cancer risk diagnosis. Even among the patients who carried a high risk of metachronous gastric cancer, cancer risk stratification was achieved. The strong influence of methylation accumulation on gastric cancer risk indicated a large contribution of aberrant DNA methylation to H. pylori infection-induced gastric carcinogenesis. Epigenetic cancer risk diagnosis is now becoming real. Citation Format: Masahiro Maeda, Takeshi Nakajima, Ichiro Oda, Taichi Shimazu, Nobutake Yamamichi, Takao Maekita, Kiyoshi Asada, Chizu Yokoi, Takayuki Ando, Takeichi Yoshida, Sohachi Nanjo, Mitsuhiro Fujishiro, Takuji Gotoda, Masao Ichinose, Toshikazu Ushijima. High impact of methylation accumulation on cancer risk: 5-year follow-up of a multicenter prospective cohort study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-092. doi:10.1158/1538-7445.AM2017-LB-092