title: Mandatory fortification with folic acid in the United States is not associated with changes in the degree or the pattern of global DNA methylation in cells involved in cervical carcinogenesis.
abstract: The purpose of this study was to evaluate whether mandatory fortification of grain products with folic acid in the USA is associated with changes in global DNA methylation in cells involved in cervical carcinogenesis. Archived specimens of cervical intraepithelial neoplasia (CIN) diagnosed before (1990-92) and after mandatory folic acid fortification (2000-02) were used to examine for global DNA methylation in specific lesions involved in cervical carcinogenesis by using a monoclonal antibody specific for 5 methyl cytosine (5-mc). The total number of lesions examined was 152 in the pre-fortification period and 172 in the post-fortification period. Immunohistochemical staining for 5-mc, the assessment of methylation status and data entry were blinded with regard to the fortification status. Age- and race-adjusted mean percentage of cells positive for 5-mc or the 5-mc score was not significantly different (P>0.05) between the pre- and post fortification periods in any of the individual lesions evaluated (i.e., normal cervical epithelium, reactive cervical epithelium, metaplastic cervical epithelium, CIN or carcinoma in situ). The degree of global DNA methylation was significantly higher (P<0.0001) in >or= CIN 2 lesions compared to <or= CIN 1 lesions, regardless of the fortification group. These results suggest that mandatory fortification with folic acid in the United States has not resulted in a change in the degree or the pattern of global DNA methylation in cells involved in cervical carcinogenesis.
authors.affiliation: Department of Nutrition Sciences, The University of Alabama at Birmingham, AL 35294, USA. piyathic@uab.edu
authors.forename: Chandrika J
authors.initials: CJ
authors.lastname: Piyathilake
authors.forename: Maria
authors.initials: M
authors.lastname: Azrad
authors.forename: Darshana
authors.initials: D
authors.lastname: Jhala
authors.forename: Maurizio
authors.initials: M
authors.lastname: Macaluso
authors.forename: Edmond K
authors.initials: EK
authors.lastname: Kabagambe
authors.forename: Ilene
authors.initials: I
authors.lastname: Brill
authors.forename: Alain
authors.initials: A
authors.lastname: Niveleau
authors.forename: Nirag
authors.initials: N
authors.lastname: Jhala
authors.forename: William E
authors.initials: WE
authors.lastname: Grizzle
mesh_terms: D044503:5-Methylcytosine / Q000032:analysis / Q000276:immunology; D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced* / Q000235:genetics; D019175:DNA Methylation; D002523:Edible Grain / Q000009:adverse effects*; D005260:Female; D005492:Folic Acid / Q000009:adverse effects*; D005527:Food, Fortified / Q000009:adverse effects*; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D014481:United States; D002583:Uterine Cervical Neoplasms / Q000139:chemically induced* / Q000235:genetics; D002578:Uterine Cervical Dysplasia / Q000139:chemically induced* / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D044503:5-Methylcytosine; D005492:Folic Acid