Abstract LB-095: Genome-wide methylation in colorectal cancer and obesity

Abstract

Abstract Purpose: The purpose of this new ground-breaking project is to identify different methylation patterns across human genome for oncogenes and genes in the methylation pathways for cancer prevention. Background: Chronic health conditions can lead to cancer with altered epigenetics cardiovascular phenotypes including differential methylation and gene expression patterns that affect health outcomes. In addition to oncogenes, we examined genes in the methylation pathways for cancer prevention. Method: We included subjects from a family-based case-control study for CRC patients and their matched healthy family members, and obese subjects and matched lean controls (n=5 each group) by accessing publically available GEO data, using reduced representation bisulfite sequencing (RRBS). Blood specimen and data processing were completed by using standardized quality programming and analysis. The average coverage of nucleotides was 3.9% of genome. Comparative analyses were performed with a difference of >10% of differentially methylated regions (DMR) between various case and control samples. Results: Few genes in the inflammatory-methylation and obesity pathways such as NOS3, AHCY, MTHFD1, FGR, MiR3648, and MiR4285 had higher methylation levels in the promoter regions than that in the intron regions, as contrary to the majority of other genes. The methylation levels for DMRs of NOS3 gene was higher in the cancer group than other groups for intron region, and PEMT gene was lowest in the cancer group than in other groups in the promoter region, for inflammation and homocysteine toxicity in the cancer group. The patterns for the most validated SEPT9 oncogene was replicated for the cancer group, and extended to other chronic health and heredity conditions in this study; methylation levels in the promoter regions progressively decreased from lean control group to obese group, then to CRC family group, and finally the CRC group, indicating higher oncogene activity. The methylation levels for all mismatch repair genes that are known to cause hereditary Lynch syndrome for CRC were highest in the intron regions, with the microsatellite instability to repair gene mutations. Methylation in DMRs for MSH2 and MSH6 mismatch repair genes were higher in the cancer group than other groups. In addition, methylation rates of the DMRs in few obesity related genes such as HK3 and CAMK1 were also progressively increasing along the health continuum, highest in cancer group. NIH’s David Bioinformatics Resources were used to identify significant biological processes and pathway analyses, related to various metabolic processes. Conclusion: Our study is one of the first studies to present the altered DNA methylation profiles across gene regions in human genome for cardiovascular phenotype in health continuum leading to cancer. Further studies are needed on metabolomic studies to promote health and to prevent cancer. Citation Format: S. Pamela Shiao, Haiyan Xiao, Lixin Dong, Lufei Young. Genome-wide methylation in colorectal cancer and obesity [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-095. doi:10.1158/1538-7445.AM2017-LB-095