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
Affiliations: [a] Department of Nutrition Sciences, The University of Alabama at Birmingham, AL 35294, USA | [b] Department of Pathology, The University of Alabama at Birmingham, AL 35294, USA | [c] School of Public Health, The University of Alabama at Birmingham, AL 35294, USA | [d] Laboratory of Virology, Faculty of Medicine, University Joseph Fourier of Grenoble, Avenue Gresivaudan, 38706 La Tronche, France
Correspondence:
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Corresponding author: Chandrika J. Piyathilake, Department of Nutrition Sciences, Division of Nutritional Biochemistry and Genomics, University of Alabama at Birmingham (UAB), University Station, Birmingham, AL 35294, USA. Tel.: +1 205 975 5398; Fax: +1 205 996 2859; E-mail: piyathic@uab.edu.
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 ⩾ CIN 2 lesions compared to ⩽ 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.
