Folate, a water-soluble B vitamin, has recently garnered much attention because of its purported role in the pathogenesis of cardiovascular disease, neural tube defects, and cancer of certain organs. Although the appreciation of the role of folate in carcinogenesis is a recent development, several previous observations have suggested a possible relationship between folate deficiency and the development of cancer. Cytopathologists in the 1950s and 1960s noticed cytologic similarities between exfoliated macrocytic gastric and cervical epithelial cells in individuals with folate and/or vitamin B 12 deficiency and dysplastic cells. Some of these macrocytic epithelial cells persisted even after the correction of folate and/or vitamin B 12 deficiency. Because the cytologic appearance of these cells had some features of malignancy, it was postulated that these abnormal cells might be a transitional cell type between normal and neoplastic epithelium. However, a functional similarity between megaloblastic and neoplastic epithelial cells was not fully appreciated until recently.
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