title: PEG1/MEST and IGF2 DNA methylation in CIN and in cervical cancer.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: Department of Obstetrics and Gynecology, Program of Cancer Detection, Prevention and Control, Duke University School of Medicine, P.O. Box 104006, Durham, NC, 27710, USA, adriana.vidal@duke.edu.
authors.forename: A C
authors.initials: AC
authors.lastname: Vidal
authors.forename: N M
authors.initials: NM
authors.lastname: Henry
authors.forename: S K
authors.initials: SK
authors.lastname: Murphy
authors.forename: O
authors.initials: O
authors.lastname: Oneko
authors.forename: M
authors.initials: M
authors.lastname: Nye
authors.forename: J A
authors.initials: JA
authors.lastname: Bartlett
authors.forename: F
authors.initials: F
authors.lastname: Overcash
authors.forename: Z
authors.initials: Z
authors.lastname: Huang
authors.forename: F
authors.initials: F
authors.lastname: Wang
authors.forename: P
authors.initials: P
authors.lastname: Mlay
authors.forename: J
authors.initials: J
authors.lastname: Obure
authors.forename: J
authors.initials: J
authors.lastname: Smith
authors.forename: B
authors.initials: B
authors.lastname: Vasquez
authors.forename: B
authors.initials: B
authors.lastname: Swai
authors.forename: B
authors.initials: B
authors.lastname: Hernandez
authors.forename: C
authors.initials: C
authors.lastname: Hoyo
mesh_terms: D000328:Adult; D019175:DNA Methylation; D005260:Female; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000150:complications* / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000235:genetics* / Q000821:virology
chemical_list: C035170:IGF2 protein, human; D011506:Proteins; C103637:mesoderm specific transcript protein; D007335:Insulin-Like Growth Factor II