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Title: Role of Various Variants of Phase 1 Xenobiotic Metabolizing Genes in Esophageal Cancer Etiology in Kashmir
Researcher: Bhat, Gulzar Ahmad
Guide(s): Dar, Nazir Ahmad and Akbar Masood
Keywords: Etiology, Genotypes, Kashmir
Xenobiotic Metabolizing Enzymes (XMEs), Esophageal Cancer, Genetic polymorphisms
University: University of Kashmir
Completed Date: 2014
Abstract: Genetic polymorphisms of phases I xenobiotic metabolizing enzymes (XMEs) are known to contribute considerably to interindividual variations in the metabolism of life style and diet specific carcinogens like polycyclic aromatic hydrocarbons and nitrosamines, hence their association with altered risk of esophageal squamous cell carcinoma (ESCC). The frequency of functionally important genotypes of genes coding for XMEs shows a wide ethnic variation. However, little is known of the frequency distribution of the major allelic variants of phase-1 XMEs in Kashmiri population. Therefore, the study analyzed the relationship between genetic polymorphisms of cytochromes P450 (CYP) 2A6a, 2A6b, 2A6c, 2A13, 2C19, 2D6, 2A6E1, 2E1ba and CYP1A1 and ESCC in Kashmir, India. The different genotypes of these genes were examined by polymerase chain reaction and restriction fragment length polymorphism in 492 ESCC cases and equal number of matched controls. Genotyping results were validated by sequencing 10 % of the samples. Conditional logistic regression models were used to assess the association of various genotypes with ESCC, gene-gene and gene-environment interactions. The ESCC vulnerable allele of all the genes were found at significantly higher frequencies in cases than controls, indicating their role as risk modifying factors in ESCC. Inverse associations with ESCC were observed in variant genotypes of CYP2A6c (OR = 0.60; 95% CI = 0.36 0.96) and CYP2A13 (OR = 0.53; 95% CI = 0.31 0.89) separately as well as when CYP2A13 genotype was present in combination with variant genotypes of CYP2A6 gene (OR = 0.31; 95% CI = 0.11 0.87). However, the variant genotypes of CYP2C19 gene (OR = 3.33; 95 % CI = 1.98 5.61) and CYP2D6 gene (OR = 2.12; 95 %CI = 1. 11 4.03) were significantly associated with the development of ESCC in alone but, in combination with protective CYP2A6 variant genotypes the risk did not persist in CYP2C19 variant genotype (OR = 0.31; 95 %CI = 0.12 0.81) genotypes. High risk of ESCC was found in ........
Appears in Departments:Department of Biochemistry

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02_certificate.pdf182.11 kBAdobe PDFView/Open
03_abstract.pdf189.21 kBAdobe PDFView/Open
04_decleration.pdf13.8 kBAdobe PDFView/Open
05_acknowledgment.pdf104.34 kBAdobe PDFView/Open
06_contents.pdf218.49 kBAdobe PDFView/Open
07_list_of_tables.pdf154.54 kBAdobe PDFView/Open
08_list_of _figures.pdf153.09 kBAdobe PDFView/Open
09_abbreviations.pdf110.05 kBAdobe PDFView/Open
10_chapter 1.pdf450.71 kBAdobe PDFView/Open
11_chapter 2.pdf474.99 kBAdobe PDFView/Open
12_chapter 3.pdf524.01 kBAdobe PDFView/Open
13_chapter 4.pdf896.47 kBAdobe PDFView/Open
14_chapter 5.pdf241.44 kBAdobe PDFView/Open
15_conclusion.pdf5.1 kBAdobe PDFView/Open
16_references.pdf238.37 kBAdobe PDFView/Open

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