A Dietary Pattern Associated with LINE-1 Methylation Alters the Risk of Developing Cervical Intraepithelial Neoplasia

Abstract

There is a paucity of research examining the relationships between dietary patterns (DPs) and risk of developing pre-cancerous lesions as well as biomarkers associated with such DPs. The purpose of the current study was to identify DPs that are associated with higher grades of cervical intraepithelial neoplasia (CIN 2+) and to determine whether these DPs are associated with the degree of DNA methylation in the long interspersed nucleotide elements (L1s) of peripheral blood mononuclear cells (PBMCs), a biomarker associated with risk of developing CIN 2+. Study population consisted of 319 child-bearing age women. DPs were derived by factor analysis. The degree of PBMC L1 methylation was assessed by pyrosequencing. Logistic regression models were used to evaluate the associations between DPs and CIN 2+. Similar models were used to evaluate the association between DPs and degree of PBMC L1 methylation in women free of CIN 2+. Women with the unhealthiest DP were 3.5 times more likely to be diagnosed with CIN 2+ compared to women with the healthiest DP (OR=3.5; 95% CI, 1.2–10.1; P=0.02). Women at risk for developing CIN 2+ with the healthiest DP were 3.3 times more likely to have higher PBMC L1 methylation compared to women with the unhealthiest DP (OR=3.3; 95% CI, 1.0–10.6; P=0.04). Our findings suggest that HPV associated risk of developing CIN 2+ may be reduced by improving DPs. The degree of PBMC L1 methylation may serve as a biomarker for monitoring the effectiveness of dietary modifications needed for reducing the risk of CIN 2+.

Mitochondria in Health and Disease – 3rd Annual Conference of Society for Mitochondrial Research and Medicine – 19–20 December 2013 — Bengaluru, India

“…In support of this hypothesis, Chandrika Piyathilake has shown that dietary pattern was significantly related to both risk of developing cervical intraepithelial neoplasia and with methylation of LINE-1. This highlights the usability of LINE-1 methylation to be used as a biomarker associated with risk of developing this type of neoplasms (Piyathilake et al, 2012).…”

Integrated approach of nutritional and molecular epidemiology, mineralogical and chemical pollutant characterisation: the protocol of a cross-sectional study in women

“…The LINE-1 methylation level in lymphocytes will be measured by pyrosequencing-based methylation analysis in three CpG sites of the LINE-1 promoter (GeneBank accession no. x58075), after DNA bisulfite conversion 15. The degree of LINE-1 methylation will be reported for each locus as well as the average percentage of methylation of the three evaluated.…”

“…Conversely, low fruit intake and folate deficiency were shown to be independent risk factors associated with low LINE-1 methylation levels 19. In women with high grade cervical intraepithelial neoplasia (CIN), LINE-1 hypomethylation was shown to be influenced by methyl donor micronutrient intake, including folate,20 and thus a healthy diet may reduce the risk of CIN through higher LINE-1 methylation levels 15…”

Epigenomics, Pharmacoepigenomics, and Personalized Medicine in Cervical Cancer

“…Piyathilake et al . [42] showed that dietary pattern influences LINE1 methylation and risk of developing premalignant lesions. Folate is known to regulate various biological processes such as DNA repair and methylation.…”