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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
PEG1/MEST and IGF2 DNA methylation in CIN and in cervical cancer
Clinical and Translational Oncology, Volume 16, No. 3, Year 2014
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Description
Introduction: Although most invasive cervical cancer (ICC) harbor <20 human papillomavirus (HPV) genotypes, use of HPV screening to predict ICC from HPV has low specificity, resulting in multiple and costly follow-up visits and overtreatment. We examined DNA methylation at regulatory regions of imprinted genes in relation to ICC and its precursor lesions to determine if methylation profiles are associated with progression of HPV-positive lesions to ICC. Materials and methods: We enrolled 148 controls, 38 CIN and 48 ICC cases at Kilimanjaro Christian Medical Centre from 2008 to 2009. HPV was genotyped by linear array and HIV-1 serostatus was tested by two rapid HIV tests. DNA methylation was measured by bisulfite pyrosequencing at regions regulating eight imprinted domains. Logistic regression models were used to estimate odd ratios. Results: After adjusting for age, HPV infection, parity, hormonal contraceptive use, and HIV-1 serostatus, a 10 % decrease in methylation levels at an intragenic region of IGF2 was associated with higher risk of ICC (OR 2.00, 95 % CI 1.14-3.44) and cervical intraepithelial neoplasia (CIN) (OR 1.51, 95 % CI 1.00-2.50). Methylation levels at the H19 DMR and PEG1/MEST were also associated with ICC risk (OR 1.51, 95 % CI 0.90-2.53, and OR 1.44, 95 % CI 0.90-2.35, respectively). Restricting analyses to women >30 years further strengthened these associations. Conclusions: While the small sample size limits inference, these findings show that altered DNA methylation at imprinted domains including IGF2/H19 and PEG1/MEST may mediate the association between HPV and ICC risk. © 2013 The Author(s).
Authors & Co-Authors
Vidal, A. C.
United States, Durham
Duke University
Henry, N. M.
United States, Durham
Duke University
Murphy, Susan K.
United States, Durham
Duke University
Oneko, Olola Achieng
Tanzania, Moshi
Kilimanjaro Christian Medical Centre
Nye, M.
United States, Durham
Duke University
Bartlett, John A.
United States, Durham
Duke University School of Medicine
Overcash, F.
United States, Durham
Duke University
Huang, Z.
United States, Durham
Duke University
Wang, Frances F.
United States, Durham
Duke Cancer Institute
Mlay, Pendo S.
Tanzania, Moshi
Kilimanjaro Christian Medical Centre
Obure, Joseph
Tanzania, Moshi
Kilimanjaro Christian Medical Centre
Smith, Jennifer Susan
United States, Chapel Hill
The University of North Carolina at Chapel Hill
Vasquez, B.
Tanzania, Moshi
Kilimanjaro Christian Medical Centre
United States, Durham
Duke University
Swai, Britta
Tanzania, Moshi
Kilimanjaro Christian Medical Centre
Hernandez, Brenda Y.
United States, Honolulu
University of Hawaiʻi Cancer Center
Hoyo, Cathrine
United States, Durham
Duke University
Statistics
Citations: 51
Authors: 16
Affiliations: 6
Identifiers
Doi:
10.1007/s12094-013-1067-4
ISSN:
1699048X
e-ISSN:
16993055
Research Areas
Cancer
Genetics And Genomics
Infectious Diseases
Sexual And Reproductive Health
Study Design
Cohort Study
Participants Gender
Female