title: Population-based case-control study on DAPK1, RAR-β2 and MGMT methylation in liquid-based cytology.
abstract: OBJECTIVE
  Methylated genes have the potential to provide a new generation of cancer biomarkers. The aim of this study was to investigate: (1) the promoter methylation status of DAPK1, RAR-β2 and MGMT in randomly selected normal cytology of the general female population; (2) the effectiveness of gene methylation in liquid-based cytology to help in the early diagnosis of HSIL; (3) the relationship between HPV infection and gene methylation.
  
  
  METHODS
  Methylation of DAPK1, RAR-β2 and MGMT in 667 cervical samples with 331 cases of abnormal cytology and 336 randomly selected normal cytology controls was detected by methylation-specific PCR and denaturing high-performance liquid chromatography method (MSP-DHPLC). The methylation frequencies of each gene were compared.
  
  
  RESULTS
  Methylation frequencies for MGMT, RAR-β2 and DAPK1 in normal cytology were 36.9, 42.0 and 46.7%, respectively. There was a trend toward increasing methylation frequency for any gene with age (p = 0.0133). Among abnormal cytology, there was a trend toward increasing number of methylation of any gene with severity of cytology grade (r = 0.1178, p = 0.0026). Methylation frequencies for MGMT and RAR-β2 among cytology of each grade were significantly different (χ ( 2 ) = 6.8976, p = 0.0086; χ ( 2 ) = 33.2477, p < 0.0001), and methylation frequencies for RAR-β2 in ASC were significantly higher than that in negative cytology (χ ( 2 ) = 8.7128, p = 0.0032). The relationship between MGMT, RAR-β2 and DAPK1 gene methylation and HPV infection was not found.
  
  
  CONCLUSIONS
  This study reported methylation frequencies for MGMT, RAR-β2 and DAPK1 in normal cytology of the general female population. The combination of MGMT methylation, cytology and HPV infection is preferable for early detection of CIN2+ in cytology samples. There was no relationship between MGMT, RAR-β2 and DAPK1 gene methylation and HPV infection.
authors: Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College/Chinese Academy of Medical Sciences, Beijing, China.
authors: Lu-Lu
authors: LL
authors: Sun
authors: Dong-yan
authors: DY
authors: Cao
authors: Jia-xin
authors: JX
authors: Yang
authors: Hui
authors: H
authors: Li
authors: Xian-rong
authors: XR
authors: Zhou
authors: Zhi-qin
authors: ZQ
authors: Song
authors: Xue-mei
authors: XM
authors: Cheng
authors: Jie
authors: J
authors: Chen
authors: Keng
authors: K
authors: Shen
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics*; D016022:Case-Control Studies; D002584:Cervix Uteri / Q000473:pathology; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D064550:Death-Associated Protein Kinases; D005260:Female; D006801:Humans; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000235:genetics*; D011401:Promoter Regions, Genetic; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000473:pathology; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000473:pathology
chemical_list: D051017:Apoptosis Regulatory Proteins; D018168:Receptors, Retinoic Acid; D025521:Tumor Suppressor Proteins; C540966:retinoic acid receptor, beta2, human; D015254:DNA Modification Methylases; C515491:MGMT protein, human; C579096:DAPK1 protein, human; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D045643:DNA Repair Enzymes