title: Global DNA methylation in a population with aflatoxin B1 exposure.
abstract: We previously reported that global DNA hypomethylation, measured as Sat2 methylation in white blood cells (WBC), and aflatoxin B1 (AFB1) exposure were associated with increased hepatocellular carcinoma risk. In this study, we assessed the association between AFB1 exposure and global DNA methylation. We measured LINE-1 and Sat2 methylation in WBC DNA samples from 1140 cancer free participants of the Cancer Screening Program (CSP) cohort. Blood and urine samples were used to determine the level of AFB1-albumin (AFB1-Alb) adducts and urinary AFB1 metabolites. In continuous models, we found reverse associations of urinary AFB1 with LINE-1 and Sat2 methylation. The odds ratio (OR) per 1 unit decrease were 1.12 (95%CI = 1.03-1.22) for LINE-1 and 1.48 (95%CI = 1.10-2.00) for Sat2 methylation. When compared with subjects in the highest quartile of LINE-1, we found that individuals in the 2nd and 3rd quartiles were less likely to have detectable AFB1-Alb adducts, with ORs (95%CI) of 0.61 (0.40-0.93), 0.61 (0.40-.94), and 1.09 (0.69-1.72), respectively. The OR for detectable AFB1-Alb was 1.81 (95%CI = 1.15-2.85) for subjects in the lowest quartile of Sat2 methylation. The OR for detection of urinary AFB1 for those with LINE-1 methylation in the lowest quartile compared with those in the highest quartile was 1.87 (95%CI = 1.15-3.04). The corresponding OR was 1.75 (95%CI = 1.08-2.82) for subjects in the lowest quartile of Sat2 methylation. The association between AFB1 exposure and global DNA methylation may have implications for the epigenetic effect of AFB1 on hepatocellular carcinoma development and also suggests that changes in DNA methylation may represent an epigenetic biomarker of dietary AFB1 exposure.
authors.affiliation: Department of Environmental Health Sciences; Mailman School of Public Health of Columbia University; New York, NY USA.
authors.forename: Hui-Chen
authors.initials: HC
authors.lastname: Wu
authors.forename: Qiao
authors.initials: Q
authors.lastname: Wang
authors.forename: Hwai-I
authors.initials: HI
authors.lastname: Yang
authors.forename: Wei-Yann
authors.initials: WY
authors.lastname: Tsai
authors.forename: Chien-Jen
authors.initials: CJ
authors.lastname: Chen
authors.forename: Regina M
authors.initials: RM
authors.lastname: Santella
mesh_terms: D000123:Acetyltransferases / Q000235:genetics; D000328:Adult; D016604:Aflatoxin B1 / Q000097:blood / Q000633:toxicity* / Q000652:urine; D014408:Biomarkers, Tumor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000209:etiology; D015331:Cohort Studies; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D015894:Genome, Human; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D000099228:Diamine N-Acetyltransferase
chemical_list: D000123:Acetyltransferases; D016604:Aflatoxin B1; D014408:Biomarkers, Tumor; D000099228:Diamine N-Acetyltransferase
keywords: DNA methylation; Hepatitis B virus; LINE-1; Sat2; aflatoxin B1; global DNA methylation; white blood cell