Abstract 249: Genome-scale analysis of aberrant DNA methylation for emerging, high incidence of colorectal cancer in Taiwan

Abstract

Abstract Background: The incidence of colorectal cancer (CRC) in Taiwan is increasing in decades, and the definite etiology remains elusive. This study aimed to explore the association of aberrant DNA methylations and the development of colorectal cancer in Taiwan. Materials and methods: We prospectively collected 27 CRC patients' tumors, the adjacent normal colons (frozen specimens), and clinical characteristics, including age, sex, body mass index (BMI), stage at diagnosis and medical history of diabetes mellitus and hyperlipidemia. We conducted a genome-scale analysis of DNA methylation in these 27 CRC and 5 adjacent normal colon samples by using Illumina Methylation EPIC Beadchips. We used Wilcoxon rank-sum test (p < 0.05) and β value difference (≧ 0.25 or ≦ -0.25) to evaluate the methylation differences between CRC and adjacent normal colon samples. Results: Overall, 7,672 differentially methylated genes (DMGs) were found between 27 CRCs and 5 adjacent normal colons. Principle component analysis demonstrated that a distinct cluster of adjacent normal colon and CRC tissue samples. Pathway analysis (β value difference ≧ 0.4 or ≦ -0.4) showed that ERK/MAPK signaling, GP6 signaling, CREB signaling in neurons, CDK5 and IGF-1 pathways were the top 5 pathways that were involved by DMGs. Subgroup analysis revealed most DMGs (N = 5,228) are shared by all 3 subgroups, however, patients who had metabolic syndrome had fewest subgroup-specific DMGs between tumors and adjacent normal colons, compared to patients who had no metabolic syndrome with normal weight or overweight (BMI < 25 or ≧ 25). Conclusion: We demonstrated a genome-scale difference of aberrant DNA methylation in colorectal cancer in an East Asian population. These data will be validated further in a larger cohort. Citation Format: KuoHsing Chen, Liang-Chuan Lai, Hsien-Fang Chang, Yu-Liang Chao, Been-Ren Lin, Jin-Tung Liang, Ann-Lii Cheng, Eric Y. Chuang, Kun-Huei Yeh. Genome-scale analysis of aberrant DNA methylation for emerging, high incidence of colorectal cancer in Taiwan [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 249.