p53 mutation profile of squamous cell carcinomas of the esophagus in Kashmir (India): A high-incidence area

Authors

  • Mohammad Muzaffar Mir,

    1. Department of Clinical Biochemistry, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Jammu and Kashmir
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  • Nazir Ahmad Dar,

    1. Department of Clinical Biochemistry, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Jammu and Kashmir
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    • The second and third authors contributed equally to this paper.

  • Sailesh Gochhait,

    1. National Centre of Applied Human Genetics, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India
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    • The second and third authors contributed equally to this paper.

  • Showkat Ali Zargar,

    1. Department of Gastroenterology, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Jammu and Kashmir
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  • Abdul Gani Ahangar,

    1. Department of Cardiovascular Thoracic Surgery, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Jammu and Kashmir
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  • R.N.K. Bamezai

    Corresponding author
    1. National Centre of Applied Human Genetics, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India
    • National Centre of Applied Human Genetics, School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India
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    • Fax: +91-011-26103211


Abstract

Esophageal squamous cell carcinoma (ESCC) has been reported to show geographical variation in its incidence, even within areas of ethnic homogeneity. Kashmir valley, in north of India, has been described as a high-risk area for ESCC. Here, we make a preliminary attempt to study mutations in exons 5–8 (the DNA binding domain) of the tumor suppressor gene, p53, in 55 ESCC patients from Kashmir. Polymerase chain reaction followed by direct sequencing analysis revealed the presence of mutations in 36.36% (20/55) tumors, assessed for the extent of allelic instability. The 20 mutations, found in 20 patients, comprised of 17 single-base substitutions (11 transitions + 6 transversions) and 3 deletions. The 17 single-base variations represented 12 missense mutations, 2 nonsense mutations and 3 variations located in intron 6, 1 of which resulted in a splicing variant. The patients when compared for the incidence of p53 mutation with various demographic features revealed females to be at increased risk (p = 0.016; OR = 4.13; 95% CI = 1.26–13.46). Comparison of mutation profile with other high-risk areas reflected both differences and similarities indicating coexposure to a unique set of risk factors. This might be due to the special dietary and cultural practices of Kashmir that needs validation, as does the gender-based difference in the incidence of p53 mutation observed in this study. © 2005 Wiley-Liss, Inc.

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