Aberrant promoter methylation and reduced expression of p16 gene in esophageal squamous cell carcinoma from Kashmir valley: a high-risk area

  • Irfana Salam
  • Showket Hussain
  • Mohammad Muzaffar Mir
  • Nazir Ahmad Dar
  • Safiya Abdullah
  • Mushtaq Ahmad Siddiqi
  • Riyaz Ahmad Lone
  • Showkat Ahmad Zargar
  • Shashi Sharma
  • Suresh Hedau
  • Seemi Farhat Basir
  • Alok Chandra Bharti
  • Bhudev C. Das


Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent cancer in Jammu and Kashmir region of India and has multi-factorial etiology involving dietary habits, genetic factors, and gene environmental interactions. Inactivation of the p16 gene expression by aberrant promoter methylation plays an important role in the progression of esophageal carcinoma. In the present investigation, we have studied the role of p16 promoter methylation in 69 histopathologically confirmed ESCC tissues and compared it with corresponding normal adjacent tissues for DNA methylation in the CpG island in the p16 promoter region by methylation-specific polymerase chain reaction (MSP) and p16 protein expression by immunoblotting. The results showed loss of p16 expression in 67% (46/69) of tumor tissues compared to only 3% in control tissues (2/69). Promoter methylation was observed in 52% (36/69) of tumor tissues and it gradually increased with the increasing severity of histological grades of the cancer (P = 0.0001). Loss of p16 expression with promoter methylation was observed in 26 of 36 cases (72%). Analysis of patients dietary habits revealed a strong association between promoter methylation and high consumption of hot salted tea (P < 0.05) which is a most favourite drink commonly consumed by Kashmiri people.


Promoter methylation Methylation-specific Polymerase chain reaction (MSP) p16 Esophageal squamous cell carcinoma (ESCC) Kashmir 



The work was supported by institutional grants from Indian Council of Medical Research (ICMR), New Delhi. Fellowship support to IS by Sher-I-Kashmir Institute of Medical Science, Kashmir, India and to SH by ICMR. This work is carried out by IS and SH—who collected samples, and performed all experiments and primary manuscript writing.


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Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Irfana Salam
    • 1
  • Showket Hussain
    • 2
  • Mohammad Muzaffar Mir
    • 1
  • Nazir Ahmad Dar
    • 1
  • Safiya Abdullah
    • 1
  • Mushtaq Ahmad Siddiqi
    • 3
  • Riyaz Ahmad Lone
    • 4
  • Showkat Ahmad Zargar
    • 5
  • Shashi Sharma
    • 6
  • Suresh Hedau
    • 2
  • Seemi Farhat Basir
    • 7
  • Alok Chandra Bharti
    • 2
  • Bhudev C. Das
    • 2
    • 8
  1. 1.Department of Clinical BiochemistrySher-I-Kashmir Institute of Medical SciencesSrinagarIndia
  2. 2.Division of Molecular OncologyInstitute of Cytology and Preventive Oncology (ICMR)NoidaIndia
  3. 3.Department of Immunology and Molecular MedicineSher-I-Kashmir Institute of Medical SciencesSrinagarIndia
  4. 4.Department of Cardiovascular Thoracic SurgerySher-I-Kashmir Institute of Medical SciencesSrinagarIndia
  5. 5.Department of GastroenterologySher-I-Kashmir Institute of Medical SciencesSrinagarIndia
  6. 6.Department of StatisticsInstitute of Cytology and Preventive Oncology (ICMR)NoidaIndia
  7. 7.Department of BiosciencesJamia Millia IslamiaNew DelhiIndia
  8. 8.Dr. B.R. Ambedkar Research Centre for Biomedical Research (ACBR) University of Delhi (North Campus)DelhiIndia

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