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World J Gastroenterol. Jul 7, 2006; 12(25): 4033-4037
Published online Jul 7, 2006. doi: 10.3748/wjg.v12.i25.4033
A study on p53 gene alterations in esophageal squamous cell carcinoma and their correlation to common dietary risk factors among population of the Kashmir valley
Imtiyaz Murtaza, Dhuha Mushtaq, Mushtaq A Margoob, Amit Dutt, Nisar Ahmad Wani, Ishfaq Ahmad, Mohan Lal Bhat
Imtiyaz Murtaza, Ishfaq Ahmad, Biochemistry and Molecular Biotechnology Laboratory, Division of PHT, S.K. University of Agricultural Sciences and Technology of Kashmir, Shalimar Campus, Srinagar, Kashmir, India
Dhuha Mushtaq, Department of Biotechnology, University of Kashmir, Srinagar, Kashmir, India
Mushtaq A Margoob, Department of Psychiatry, Government Medical College, Srinagar, Kashmir, India
Amit Dutt, Broad Institute of Harvard and MIT, 320 Charles St, Cambridge, MA-02141, United States
Nisar Ahmad Wani, Department of Surgery, Government Medical College, Srinagar, Kashmir, India
Mohan Lal Bhat, Department of Pathology, Government Medical College, Srinagar, Kashmir, India
Author contributions: All authors contributed equally to the work.
Supported by funding (100%) from the Department of Science and Technology, New Delhi through the Fast Track Young Scientist Project Award to Dr. Imtiyaz Murtaza, No. SR/FTP/LS-A-91/2001
Correspondence to: Dr. Imtiyaz Murtaza, Assistant Professor (Biochemistry), Division of PHT, SKUAST (K), Shalimar Campus, Srinagar, Kashmir, 191121 (J&K), India. imz_murtaza@hotmail.com
Telephone: +91-194-2424812 Fax: +91-194-2464195
Received: January 14, 2006
Revised: February 14, 2006
Accepted: February 18, 2006
Published online: July 7, 2006
Abstract

AIM: To systematically examine the extent of correlation of risk factors, such as age, consumed dietary habit and familial predisposition with somatic Tp53 molecular lesion causal to elevate carcinogenesis severity of esophageal squamous cell carcinoma (ESCC) among the Kashmiri population of Northern India.

METHODS: All cases (n = 51) and controls (n = 150) were permanent residents of the Kashmir valley. Genetic alterations were determined in exons 5-8 of Tp53 tumor suppressor gene among 45 ESCC cases histologically confirmed by PCR-SSCP analysis. Data for individual cancer cases (n = 45) and inpatient controls (n = 150) with non-cancer disease included information on family history of cancer, thirty prevailing common dietary risk factors along with patient’s age group. Correlation of genetic lesion in Tp53 exons to animistic data from these parameters was generated by Chi-square test to all 45 histologically confirmed ESCC cases along with healthy controls.

RESULTS: Thirty-five of 45 (77.8%) histologically characterized tumor samples had analogous somatic mutation as opposed to 1 of 45 normal sample obtained from adjacent region from the same patient showed germline mutation. The SSCP analysis demonstrated that most common p53 gene alterations were found in exon 6 (77.7%), that did not correlate with the age of the individual and clinicopathological parameters but showed significant concordance (P < 0.05) with familial history of cancer (CD = 58), suggesting germline predisposition at an unknown locus, and dietary habit of consuming locally grown Brassica vegetable “Hakh” (CD = 19.5), red chillies (CD = 20.2), hot salty soda tea (CD = 2.37) and local baked bread (CD = 1.1).

CONCLUSION: Our study suggests that somatic chromosomal mutations, especially in exon 6 of Tp53 gene, among esophageal cancer patients of an ethnically homogenous population of Kashmir valley are closely related to continued exposure to various common dietary risk factors, especially hot salty tea, meat, baked bread and “Hakh”, that are rich in nitrosoamines and familial cancer history.

Keywords: Case-controls; Esophageal squamous cell carcinoma; Dietary carcinogens; p53 alterations