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BMC Cancer
Published in: BMC Cancer 1/2017

Open Access 01-12-2017 | Research article

LINE-1 hypermethylation in white blood cell DNA is associated with high-grade cervical intraepithelial neoplasia

Authors: Martina Barchitta, Annalisa Quattrocchi, Andrea Maugeri, Carolina Canto, Nadia La Rosa, Maria Antonietta Cantarella, Giuseppa Spampinato, Aurora Scalisi, Antonella Agodi

Published in: BMC Cancer | Issue 1/2017

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Abstract

Background

Long Interspersed Nuclear Elements-1 (LINEs-1) methylation from white blood cells (WBCs) DNA has been proposed as biomarker associated with different types of cancer. The aim of the present study was to investigate the degree of WBCs LINE-1 methylation, according to high-risk Human Papilloma Virus (hrHPV) status in a healthy population, and the association with high-grade Cervical Intraepithelial Neoplasia (CIN2+) in hrHPV positive women.

Methods

Women with abnormal cervical cells were enrolled and classified by histological diagnosis and hrHPV infection. A structured questionnaire was used to obtain information on socio-demographic variables and lifestyle factors. LINE-1 methylation level in WBCs was measured by pyrosequencing-based methylation analysis after bisulfite conversion.

Results

Among 252 women diagnosed with normal cervical epithelium, with regard to LINE-1 methylation level no significant difference was observed between hrHPV positive and hrHPV negative women, also adjusting for known risk factors of infection. The association between WBCs LINE-1 methylation and CIN2+ status was analyzed in hrHPV positive women. The median value of LINE-1 methylation levels was higher in cases (CIN2+) than in controls (75.00% versus 73.17%; p = 0.002). For a one-unit increase in LINE-1 methylation level, the odds of being diagnosed with CIN2+ increased by 10%, adjusting for known factors related to LINE-1 methylation (adjOR: 1.10; 95% CI:1.01–1.20; p = 0.032). The Receiver-Operating Characteristic (ROC) curve analysis identified the cut-off value of 73.8% as the best threshold to separate cases from controls (sensitivity: 63.4% and specificity: 61.8%).

Conclusions

LINE-1 methylation status in WBCs DNA may represent a cost-effective and tissue-accessible biomarker for high-grade CIN in hrHPV positive women. However, LINE-1 hypermethylation cannot be considered specific for cervical cancer (CC) and a model based solely on LINE-1 methylation levels has limited performance. Further investigations are necessary to propose and validate a novel methylation biomarker panel, based on LINE-1 methylation and other differentially methylated regions, for the screening of women at risk of CC.
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Metadata
Title
LINE-1 hypermethylation in white blood cell DNA is associated with high-grade cervical intraepithelial neoplasia
Authors
Martina Barchitta
Annalisa Quattrocchi
Andrea Maugeri
Carolina Canto
Nadia La Rosa
Maria Antonietta Cantarella
Giuseppa Spampinato
Aurora Scalisi
Antonella Agodi
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2017
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-017-3582-0

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