期刊
NUTRITION
卷 27, 期 5, 页码 513-519出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.nut.2010.08.018
关键词
Methylation; Cervical; Neoplasia
资金
- National Cancer Institute [R01 CA105448]
Objective: The objective of the study was to evaluate LINE-1 methylation as an intermediate biomarker for the effect of folate and vitamin B12 on the occurrence of higher grades of cervical intraepithelial neoplasia (CIN >= 2). Methods: This study included 376 women who tested positive for high-risk human papillomaviruses and were diagnosed with CIN >= 2 (cases) or CIN <= 1 (non-cases). CIN >= 2 (yes/no) was the dependent variable in logistic regression models that specified the degree of LINE-1 methylation of peripheral blood mononuclear cells (PBMCs) and of exfoliated cervical cells (CCs) as the independent predictors of primary interest. In analyses restricted to non-cases, PBMC LINE-1 methylation (>= 70% versus <70%) and CC LINE-1 rnethylation (>= 54% versus <54%) were the dependent variables in logistic regression models that specified the circulating concentrations of folate and vitamin B12 as the primary independent predictors. Results: Women in the highest tertile of PBMC LINE-1 methylation had 56% lower odds of being diagnosed with CIN >= 2 (odds ratio 0.44, 95% confidence interval 0.24-0.83, P = 0.011), whereas there was no significant association between degree of CC LINE-1 methylation and CIN >= 2 (odds ratio 0.86, 95% confidence interval 0.51-1.46, P = 0.578). Among non-cases, women with supraphysiologic concentrations of folate (>19.8 ng/mL) and sufficient concentrations of plasma vitamin B12 (>= 200.6 ng/mL) were significantly more likely to have highly methylated PBMCs compared with women with lower folate and lower vitamin B12 (odds ratio 3.92, 95% confidence interval 1.06-14.52, P = 0.041). None of the variables including folate and vitamin B12 were significantly associated with CC LINE-1 methylation. Conclusion: These results suggest that a higher degree of LINE-1 methylation in PBMCs, a one-carbon nutrient-related epigenetic alteration, is associated with a lower risk of developing CIN. (C) 2011 Elsevier Inc. All rights reserved.
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