Affiliations: Department of Biotechnology, Panjab University,
Chandigarh, India | Department of Medical Genetics, National Institute of
Genetic Engineering and Biotechnology, Tehran, Iran | Department of Urology, Post Graduate of Medical
Education and Research, Chandigarh, India | Department of Histopathology, Post Graduate of Medical
Education and Research, Chandigarh, India
Note: [] Corresponding authors: Seyed Ali Hosseini and Ranbir Chander
Sobti, Department of Biotechnology, Panjab University, Chandigarh, 160014,
India. Tel.: +91 172 2541409; E-mail: [email protected]
Abstract: 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.
