title: Effect of aberrant promoter methylation of FHIT and RASSF1A genes on susceptibility to cervical cancer in a North Indian population.
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.
authors.affiliation: Division of Molecular Genetics and Biochemistry, Institute of Cytology and Preventive Oncology (ICMR), Noida, India.
authors.forename: M Kausar
authors.initials: MK
authors.lastname: Neyaz
authors.forename: R Suresh
authors.initials: RS
authors.lastname: Kumar
authors.forename: Showket
authors.initials: S
authors.lastname: Hussain
authors.forename: Samar H
authors.initials: SH
authors.lastname: Naqvi
authors.forename: Indu
authors.initials: I
authors.lastname: Kohaar
authors.forename: Nisha
authors.initials: N
authors.lastname: Thakur
authors.forename: Veena
authors.initials: V
authors.lastname: Kashyap
authors.forename: Bhudev C
authors.initials: BC
authors.lastname: Das
authors.forename: Syed Akhtar
authors.initials: SA
authors.lastname: Husain
authors.forename: Mausumi
authors.initials: M
authors.lastname: Bharadwaj
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000235:genetics*; D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D052162:Human papillomavirus 16 / Q000302:isolation & purification; D052161:Human papillomavirus 18 / Q000302:isolation & purification; D006801:Humans; D007194:India; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000473:pathology / Q000821:virology; D044465:White People / Q000235:genetics; D000099170:Bis(5'-adenosyl)triphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins; D000099170:Bis(5'-adenosyl)triphosphatase; C411762:RASSF1 protein, human