Effect of aberrant promoter methylation of FHIT and RASSF1A genes on susceptibility to cervical cancer in a North Indian population

Biomarkers. 2008 Sep;13(6):597-606. doi: 10.1080/13547500802078859.

Abstract

As current evidence suggests the involvement of epigenetic modification of tumour suppressor genes in human cancer, we investigated the aberrant promoter methylation of FHIT and RASSF1A genes in human papillomavirus (HPV)-mediated cervical cancer in Indian women. We analysed 60 cervical cancer tissue biopsies of different clinical stage and histological grading and 23 healthy control samples with normal cervical cytology. Methylation-specific polymerase chain reaction (MSP) was performed to analyse the methylation status of FHIT and RASSF1A genes and confirmed by sequencing. Both patients and controls were screened for HPV infection and 98% of the HPV-infected cases showed positivity for HPV type 16. Aberrant promoter methylation of the FHIT gene was found in 28.3% (17/60) of cases and of the RASSF1A gene in 35.0% (21/60) of cases; promoter methylation of both the genes was found in 13.3% (8/60) of cervical cancer cases. Methylation was significantly (p<0.01) associated with the cervical cancer cases compared with controls. None of the 23 controls was found to be methylated in either of these genes. This is the first study indicating a correlation between the promoter methylation of FHIT and RASSF1A genes and the clinical stage and histological grading of cervical carcinoma in Indian women. Future studies are underway to examine the practical implications of these findings for use as a biomarker.

MeSH terms

  • Acid Anhydride Hydrolases / genetics*
  • Adult
  • Biomarkers, Tumor / genetics*
  • Case-Control Studies
  • DNA Methylation*
  • European Continental Ancestry Group / genetics
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genetic Predisposition to Disease
  • Human papillomavirus 16 / isolation & purification
  • Human papillomavirus 18 / isolation & purification
  • Humans
  • India
  • Middle Aged
  • Neoplasm Proteins / genetics*
  • Neoplasm Staging
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic*
  • Tumor Suppressor Proteins / genetics*
  • Uterine Cervical Neoplasms / ethnology
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / virology

Substances

  • Biomarkers, Tumor
  • Neoplasm Proteins
  • RASSF1 protein, human
  • Tumor Suppressor Proteins
  • fragile histidine triad protein
  • Acid Anhydride Hydrolases