Aberrant DNA Methylation: Implications in Racial Health Disparity.
Incidence and mortality rates of colorectal carcinoma (CRC) are higher in African Americans (AAs) than in Caucasian Americans (CAs). Deficient micronutrient intake due to dietary restrictions in racial/ethnic populations can alter genetic and molecular profiles leading to dysregulated methylation patterns and the inheritance of somatic to germline mutations.



Total DNA and RNA samples of paired tumor and adjacent normal colon tissues were prepared from AA and CA CRC specimens. Reduced Representation Bisulfite Sequencing (RRBS) and RNA sequencing were employed to evaluate total genome methylation of 5'-regulatory regions and dysregulation of gene expression, respectively. Robust analysis was conducted using a trimming-and-retrieving scheme for RRBS library mapping in conjunction with the BStool toolkit.



DNA from the tumor of AA CRC patients, compared to adjacent normal tissues, contained 1,588 hypermethylated and 100 hypomethylated differentially methylated regions (DMRs). Whereas, 109 hypermethylated and 4 hypomethylated DMRs were observed in DNA from the tumor of CA CRC patients; representing a 14.6-fold and 25-fold change, respectively. Specifically; CHL1, 4 anti-inflammatory genes (i.e., NELL1, GDF1, ARHGEF4, and ITGA4), and 7 miRNAs (of which miR-9-3p and miR-124-3p have been implicated in CRC) were hypermethylated in DNA samples from AA patients with CRC. From the same sample set, RNAseq analysis revealed 108 downregulated genes (including 14 ribosomal proteins) and 34 upregulated genes (including POLR2B and CYP1B1 [targets of miR-124-3p]) in AA patients with CRC versus CA patients.



DNA methylation profile and/or products of its downstream targets could serve as biomarker(s) addressing racial health disparity.
Department of Family, Population and Preventive Medicine, Stony Brook University, Stony Brook, NY, 11794, United States of America.|Department of Biomedical Informatics, Stony Brook University, Stony Brook, NY, 11794, United States of America.|Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY, 11794, United States of America.
Xuefeng
X
Wang
Department of Family, Population and Preventive Medicine, Stony Brook University, Stony Brook, NY, 11794, United States of America.|Division of Cancer Prevention, Stony Brook University, Stony Brook, NY, 11794, United States of America.
Ping
P
Ji
Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY, 11794, United States of America.
Yuanhao
Y
Zhang
Department of Family, Population and Preventive Medicine, Stony Brook University, Stony Brook, NY, 11794, United States of America.|Division of Cancer Prevention, Stony Brook University, Stony Brook, NY, 11794, United States of America.
Joseph F
JF
LaComb
Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY, 11794, United States of America.
Xinyu
X
Tian
Department of Medicine, Stony Brook University, Stony Brook, NY, 11794, United States of America.|Division of Gastroenterology, Stony Brook University, Stony Brook, NY, 11794, United States of America.
Ellen
E
Li
Department of Family, Population and Preventive Medicine, Stony Brook University, Stony Brook, NY, 11794, United States of America.|Department of Medicine, Stony Brook University, Stony Brook, NY, 11794, United States of America.|Division of Cancer Prevention, Stony Brook University, Stony Brook, NY, 11794, United States of America.
Jennie L
JL
Williams
D003110:Colonic Neoplasms / Q000235:genetics*; D019175:DNA Methylation; D006801:Humans; D044469:Racial Groups