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Altered Folate Availability Modifies The Molecular Environment Of The Human Colon: Implications For Colorectal Carcinogenesis, Petr Protiva, Joel B. Mason, Zhenhua Liu, Michael E. Hopkins, Celeste Nelson, James R. Marshall, Richard W. Lambrecht, Swaroop Pendyala, Levy Kopelovich, Myungjin Kim, Steven H. Kleinstein, Peter W. Laird, Martin Lipkin, Peter R. Holt

Zhenhua Liu

BACKGROUND—Low folate status increases colorectal cancer risk whereas abundant supplementation may paradoxically increase risk. The mechanisms are unknown. OBJECTIVES—To define molecular pathways in the human colon altered by either dietary folate depletion (followed by repletion), or by supplementation. METHODS—10 healthy volunteers consumed a low folate diet for 12 weeks. During the last 4 weeks, folic acid (1 mg/day) was administered. In a second study, 10 other subjects were provided supplemental folic acid for 8 weeks. Rectosigmoid biopsies were obtained at measured intervals in both studies for assessment of primary endpoints: genome-wide gene expression, genomic DNA methylation, promoter methylation (depletion study …

Concentration Of Folate In Colorectal Tissue Biopsies Predicts Prevalence Of Adenomatous Polyps, Andrew Flood, Joel Mason, Zhenhua Liu, Brooks Cash, Arthur Schatzkin, Philip Schoenfeld, Amanda Cross

Zhenhua Liu

Background and aims—Folate has been implicated as a potential etiologic factor for colorectal cancer. Prior research has not adequately exploited concentrations of folate in normal colonic mucosal biopsies to examine the issue. Methods—We used logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of adenoma according to tissue concentration of folate using asymptomatic average-risk women (40–70 years) in a colorectal cancer screening study. Of the 1,593 eligible women who were offered enrollment, 1,483 (93%) participated. Colonoscopy was complete to the cecum in 98.7% (1,463/1,483) of the subjects and normal colonic tissue biopsies were obtained from 813 …

Associations Of Plasma Selenium With Arsenic And Genomic Methylation Of Leukocyte Dna In Bangladesh, Richard J. Pilsner, Megan N. Hall, Xinhua Liu, Habibul Ahsan, Vesna Ilievski, Vesna Slavkovich, Diane Levy, Pam Factor-Litvak, Joseph H. Graziano, Mary V. Gamble

J. Richard Pilsner

Background

Global hypomethylation of DNA is thought to constitute an early event in some cancers and occurs in response to arsenic (As) exposure and/or selenium (Se) deficiency in both in vitro and animal models. In addition, antagonism between As and Se, whereby each reduces toxicity of the other, has been well documented in animal models. Se status may therefore modify the health effects of As in As-exposed populations.

Objective

The primary objectives of our study were to test the hypothesis that Se deficiency is associated with genomic hypomethylation of lymphocyte DNA and to determine whether Se levels are associated with …