Abstract
The objective of this study was to evaluate whether mandatory fortification of grain products with folic acid in the USA is associated with changes in histone methylation in cells involved in cervical carcinogenesis. Cervical specimens (free of pre‐cancer or diagnosed with pre‐cancer cervical intraepithelial neoplasia grade 3 [CIN 3]) obtained before (1990‐92) or after mandatory folic acid fortification (2000‐02) were used to examine the degree of histone methylation (H3 Lys‐9) by immunohistochemistry. Age‐ and race‐adjusted mean H3 Lys‐9 score was significantly higher in CIN 3 specimens obtained in the post‐fortification period compared to pre‐fortification period (P < 0.05). In contrast, in specimens obtained from women free of CIN, H3 Lys‐9 scores were significantly lower in post‐fortification specimens compared to pre‐fortification specimens (P < 0.05). Altered histone methylation has emerged as key to DNA methylation‐related gene silencing and this type of gene silencing in cancer is accompanied by an increase in H3 Lys9 methylation. Therefore, higher Lys‐9 methylation in cervical tissues of women diagnosed with CIN 3 in the post‐fortification period compared to pre‐fortification period suggest that fortification may have adverse effects on histone methylation in already initiated cells. Lower Lys‐9 methylation in cervical cells of women free of CIN in the post fortification period compared to pre fortification on the other hand suggest that fortification is likely to protect against the initiation of carcinogenic process in the cervix.Supported by NCI R03 CA 102893
Published Version
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