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

• Published in: Biomarkers 2008-01, Vol.13 (6), p.597-606
• Main Authors: Kausar Neyaz, M., Suresh Kumar, R., Hussain, Showket, Naqvi, Samar, Kohaar, Indu, Thakur, Nisha, Kashyap, Veena, Das, Bhudev, Akhtar Husain, Syed, Bharadwaj, Mausumi
• Format: Article
• Language: English
• Subjects: Acid Anhydride Hydrolases - genetics; Adult; Biological and medical sciences; Biomarkers, Tumor - genetics; Case-Control Studies; Dermatology; DNA Methylation; European Continental Ancestry Group - genetics; Female; Female genital diseases; fragile histidine triad (FHIT); Gene Expression Regulation, Neoplastic; Genetic Predisposition to Disease; Gynecology. Andrology. Obstetrics; human papillomavirus (HPV); Human papillomavirus 16 - isolation & purification; Human papillomavirus 18 - isolation & purification; Humans; India; Infectious diseases; Medical sciences; Methylation-specific polymerase chain reaction (MSP); Middle Aged; Neoplasm Proteins - genetics; Neoplasm Staging; Polymerase Chain Reaction; Promoter Regions, Genetic; RAS association domain family 1A (RASSF1A); squamous cell carcinoma (SCC); Tumor Suppressor Proteins - genetics; Tumors; Tumors of the skin and soft tissue. Premalignant lesions; Uterine Cervical Neoplasms - ethnology; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - pathology; Uterine Cervical Neoplasms - virology; Viral diseases
• ISSN: 1354-750X; 1366-5804
• 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