HYPOMETHYLATION IN CERVICAL TISSUE - IS THERE A CORRELATION WITH FOLATE STATUS

We have shown previously that DNA hypomethylation is significantly ass ociated,vith grade of cervical intraepithelial neoplasia (CIN; Y, I. K im ef at, Cancer, 74: 893-899, 1994), The objective of this study was to further describe this relationship and to investigate the role of f olate in the observed association of DNA hypomethylation and GIN. Eigh ty-three patients with abnormal PAP smear results were referred to the Cervical Dysplasia Clinic at the University of Arizona for colposcopi c examination and biopsy. Patients completed a short questionnaire and provided a nonfasting serum sample, DNA hypomethylation was assessed by incubating DNA extracted from biopsy samples with [H-3]methyl-S-ade nosylmethionine and Sss 1 methylase, Cervical tissue and serum folate concentrations were assessed using a microbiological assay. All folate levels were log transformed prior to statistical analysis, The histol ogical distribution of the samples was: 7 adjacent normal, 30 CIN I, 1 8 CIN II, 13 CIN III, and 11 carcinoma in situ (CIS), The mean age of participants was 29.8 +/- 9.6 years. DNA hypomethylation was significa ntly different between select histological levels. Both cervical tissu e folate and serum folate levels were significantly correlated to meth ylation level (P = 0.0211 and P = 0.0569, respectively). Smoking, horm onal contraceptive use, parity, and human papillomavirus infection wer e not associated with DNA hypomethylation or folate status, The curren t use of vitamins was significantly associated with serum folate level but not with methylation or cervical folate levels. These data extend our earlier findings that DNA hypomethylation is an early event in ce rvical carcinogenesis. To conclude that the folate level is significan tly related to DNA hypomethylation, further investigation of DNA hypom ethylation of specific genes is required.