The Mandatory Fortification of Foods with Folic Acid in the United States is not associated with an Improvement in the Degree or Pattern of Global DNA Methylation in the Cervical Epithelium

Abstract

The purpose of this study was to evaluate the effects of folic acid fortification of foods on global DNA methylation (GDM) by comparing the methylation status in specific cells identified in archival specimens of cervical intraepithelial neoplasia (CIN) diagnosed prior to fortification (1990–92) and after fortification (2000–02). The degree of GDM was assessed by an immunohistochemical technique that used monoclonal antibodies specific for 5-methyl cytosine (5-mc) in 121 lesions identified in specimens of 39 women in the pre-fortification period and in 170 lesions identified in specimens of 49 women in the post-fortification period. The mean percentage of cells positive for 5-mc (age and race adjusted) was not significantly different between pre and post fortification periods in any of the lesion types (normal cervical epithelium, reactive cervical epithelium, metaplastic cervical epithelium, CIN 1, CIN 2, CIN 3 or carcinoma in situ) evaluated. The degree of GDM was significantly higher in lesions ≥ CIN 2 compared to lesions ≤ CIN 1 and this methylation pattern was similar in the pre and post fortification groups. These results suggested that the mandatory fortification with folic acid in the United States has not resulted in a change in the degree or the pattern of GDM in cells involved in the process of cervical carcinogenesis.