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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Associations between Methylation of Paternally Expressed Gene 3 (PEG3), Cervical Intraepithelial Neoplasia and Invasive Cervical Cancer
PLoS ONE, Volume 8, No. 2, Article e56325, Year 2013
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Description
Cytology-based screening for invasive cervical cancer (ICC) lacks sensitivity and specificity to discriminate between cervical intraepithelial neoplasia (CIN) likely to persist or progress from cases likely to resolve. Genome-wide approaches have been used to identify DNA methylation marks associated with CIN persistence or progression. However, associations between DNA methylation marks and CIN or ICC remain weak and inconsistent. Between 2008-2009, we conducted a hospital-based, case-control study among 213 Tanzania women with CIN 1/2/3 or ICC. We collected questionnaire data, biopsies, peripheral blood, cervical scrapes, Human papillomavirus (HPV) and HIV-1 infection status. We assessed PEG3 methylation status by bisulfite pyrosequencing. Multinomial logistic regression was used to estimate odds ratios (OR) and confidence intervals (CI 95%) for associations between PEG3 methylation status and CIN or ICC. After adjusting for age, gravidity, hormonal contraceptive use and HPV infection, a 5% increase in PEG3 DNA methylation was associated with increased risk for ICC (OR = 1.6; 95% CI 1.2-2.1). HPV infection was associated with a higher risk of CIN1-3 (OR = 15.7; 95% CI 5.7-48.6) and ICC (OR = 29.5, 95% CI 6.3-38.4). Infection with high risk HPV was correlated with mean PEG3 differentially methylated regions (DMRs) methylation (r = 0.34 p<0.0001), while the correlation with low risk HPV infection was weaker (r = 0.16 p = 0.047). Although small sample size limits inference, these data support that PEG3 methylation status has potential as a molecular target for inclusion in CIN screening to improve prediction of progression. Impact statement: We present the first evidence that aberrant methylation of the PEG3 DMR is an important co-factor in the development of Invasive cervical carcinoma (ICC), especially among women infected with high risk HPV. Our results show that a five percent increase in DNA methylation of PEG3 is associated with a 1.6-fold increase ICC risk. Suggesting PEG3 methylation status may be useful as a molecular marker for CIN screening to improve prediction of cases likely to progress. © 2013 Nye et al.
Authors & Co-Authors
Nye, M.
United States, Durham
Duke University School of Medicine
United States, Chapel Hill
The University of North Carolina at Chapel Hill
Hoyo, Cathrine
United States, Durham
Duke University School of Medicine
Huang, Z.
United States, Durham
Duke University School of Medicine
Vidal, A. C.
United States, Durham
Duke University School of Medicine
Wang, Frances F.
United States, Durham
Duke Cancer Institute
Overcash, F.
United States, Durham
Duke University School of Medicine
Smith, Jennifer Susan
United States, Chapel Hill
The University of North Carolina at Chapel Hill
Vasquez, B.
Tanzania
Kilmanjaro Christian Medical Center
United States, Durham
Duke University
Hernandez, Brenda Y.
United States, Honolulu
University of Hawaiʻi Cancer Center
Swai, Britta
Tanzania, Moshi
Kilimanjaro Christian Medical Centre
Oneko, Olola Achieng
Tanzania, Moshi
Kilimanjaro Christian Medical Centre
Mlay, Pendo S.
Tanzania, Moshi
Kilimanjaro Christian Medical Centre
Obure, Joseph
Tanzania, Moshi
Kilimanjaro Christian Medical Centre
Gammon, Marilie D.
United States, Chapel Hill
The University of North Carolina at Chapel Hill
Bartlett, John A.
United States, Durham
Duke University School of Medicine
Murphy, Susan K.
United States, Durham
Duke University School of Medicine
Statistics
Citations: 71
Authors: 16
Affiliations: 7
Identifiers
Doi:
10.1371/journal.pone.0056325
e-ISSN:
19326203
Research Areas
Cancer
Genetics And Genomics
Health System And Policy
Infectious Diseases
Sexual And Reproductive Health
Study Design
Case-Control Study
Study Locations
Tanzania
Participants Gender
Female