Promoter hypermethylation of p73 and p53 genes in cervical cancer patients among north Indian population.
Hypermethylation of CpG islands leads to transcriptional silencing and it is the predominant mechanism of tumor suppressor gene inactivation in many tumors. Methylation-specific polymerase chain reaction was performed to analyse the methylation status of the promoter region of the tumor suppressor genes. Hypermethylation of the 5' CpG island of the p21 ( CIP1 ), p27 ( KIP1 ), p57 ( KIP2 ), p53, p73 and RB 1 gene promoter were found in 8.8, 8.8, 11.2, 12, 25.6 and 4.8 % of 125 cervical cancer samples from north Indian population, respectively. Methylation of p73 was significantly (P < 0.001) associated with the cervical cancer cases in comparison to controls. Significant correlation was also observed between the methylation of p73 gene and increase in the risk of cervical cancer among passive smokers. Promoter hypermethylation of p53 gene was also observed to be significant among oral contraceptive users and cervical cancer patients having age at first sexual intercourse <20 years whereas hypermethylation of other genes was not found to be significant in the present study. This is the first report showing significant hypermethylation of p73 and p53 genes among cervical cancer patients in north Indian population. This is also the first report on significant p53 hypermethylation in cervical cancer in any population. Our findings did not show any correlation between promoter methylation of p73 and the other genes under study with clinicopathological parameters, including human papillomavirus infection and stage of the disease. The frequency of aberrant methylation of p73 and p53 gene promoter was unchanged according to the age of patients.
Department of Biotechnology, Panjab University, Chandigarh 160014, India.
Abhimanyu Kumar
AK
Jha
Mohsen
M
Nikbakht
Veena
V
Jain
Alka
A
Sehgal
Neena
N
Capalash
Jagdeep
J
Kaur
D001483:Base Sequence; D002135:Calcium-Binding Proteins / Q000235:genetics; D016022:Case-Control Studies; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D052162:Human papillomavirus 16 / Q000235:genetics; D006801:Humans; D007194:India; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic; D016160:Retinoblastoma Protein / Q000235:genetics; D028021:Sodium-Potassium-Chloride Symporters / Q000235:genetics; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000821:virology
C109198:CIB1 protein, human; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D016160:Retinoblastoma Protein; C415467:SLC12A9 protein, human; D028021:Sodium-Potassium-Chloride Symporters; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins