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Disease Markers
Volume 28, Issue 6, Pages 361-368

Frequency of P16INK4a and P14ARF Genes Methylation and Its Impact on Bladder Cancer Cases in North Indian Population

Seyed Ali Hosseini,1,2 Ranbir Chander Sobti,1 Kianoosh Malekzadeh,1 Shrawan Kumar Singh,3 and Kusum Joshi4

1Department of Biotechnology, Panjab University, Chandigarh, India
2Department of Medical Genetics, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran
3Department of Urology, Post Graduate of Medical Education and Research, Chandigarh, India
4Department of Histopathology, Post Graduate of Medical Education and Research, Chandigarh, India

Received 16 July 2010; Accepted 16 July 2010

Copyright © 2010 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Introduction: Amongst the genitourinary cancers, carcinoma of the urinary bladder is one of the leading causes of death in India. Hypermethylation of the CpG islands of gene promoter is one of the earliest and most frequent epigenetic alterations leading to cancer as well as in its development. Several studies have suggested that tumour suppressor genes play a key role in the development of cancer. Methylation in the CDKN2A has been associated with various malignant diseases, but information with respect to urinary bladder cancer is lacking in north Indian population.

Materials and methods: We analyzed the methylation of P16INK4a and P14ARF in 80 tissues and matched blood samples of patients suffering from bladder cancer and 80 blood samples of cancer-free individuals by MS-PCR.

Results: In tissue and matched blood samples of bladder cancer patients, the incidence of P14ARF hypermethylation significantly increased (OR = 0.31, 95%CI = 0.12–0.8, P = 0.01) and (OR = 0.0, 95%CI=0.0–0.62, P = 0.006) respectively with an increase in age. Clinicopathological analysis revealed that P14ARF hypermethylation in tissue and blood samples was significantly associated with invasive stage (≥ T2) (OR = 0.21, 95%CI = 0.08–0.51, P = 0.0002) and (OR = 0.09, 95%CI = 0.03–0.37, P = 0.00001) respectively. Muscle invasive tumour stage (≥T2) showed significant association with increased risk of P16INK4α promoter hypermethylation in tissue and blood samples of patients (OR = 0.38, 95%CI = 0.17–0.82, P = 0.01) and (OR = 0.13, 95%CI = 0.05–0.36, P = 0.00005) respectively.

Conclusion: These results suggest that the CpG island hypermethylation status of the defined panel of genes may be a useful biomarker in patients suffering from bladder cancer.