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An investigation into the association between cytochrome P450 and glutathione S-transferase detoxification enzyme polymorphisms and human oral squamous cell carcinoma

Worrall, Stephen Frederick (1998)
M.D. thesis, University of Birmingham.

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Abstract

Oral squamous cell carcinoma is the sixth commonest cancer in the world. Most patients who develop oral cancer are elderly males who are heavy users of tobacco and alcohol although the incidence is increasing in younger individuals and in those who neither smoke nor drink. Approximately 80% of human cancers result from exposure to xenobiotics. Over the millennia Man has evolved complex families of detoxification enzymes to metabolise and eliminate these harmful compounds. Many of the genes that code for these enzymes are polymorphic, sometimes encoding enzymes with abnormal activity profiles. Numerous diseases have been shown to be more frequent in individuals with abnormal detoxification enzyme activity. This study investigated the association between polymorphisms in cytochrome P450 and glutathione S-transferase genes and disease susceptibility in 106 patients with histologically proven squamous cell carcinoma of the oral cavity. The CYP2D6 PM phenotype was associated with a significantly increased risk of oral cancer (p = 0.0012). The CYP2D6 PM and HET phenotypes appear to be markers for a putative tumour suppressor gene at or close to 22q12. The EM phenotype is a risk factor in individuals who are heavy drinkers and smokers, possibly due to phase 1 activation of 4-(methylnitrosamino)-1-(3 pyridyl)-1-butanone.

Type of Work:M.D. thesis.
School/Faculty:Faculties (to 1997) > Faculty of Medicine and Dentistry
Department:unspecified
Subjects:RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Institution:University of Birmingham
Library Catalogue:Check for printed version of this thesis
ID Code:31
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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