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Title: Polymorphism of the glutathione S-transferase M1 and cytochrome P4501A1 genes and susceptibility to emphysema and lung cancer
Author: Cantlay, Ann M.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1997
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Deletion of GSTM1 was associated with emphysema in the presence of concomitant lung cancer, but not with lung cancer alone. No association between the GSTM1 polymorphism and either centriacinar or panacinar patterns of emphysema could be demonstrated, but a small association was found in cases with both centriacinar and panacinar emphysema. The glutathione S-transferase M1 deletion was not associated with chronic obstructive pulmonary disease, the clinical manifestation of emphysema, nor with the severe emphysema found in autopsy specimens. The cytochrome P4501A1 polymorphism was associated with emphysema concomitant with lung cancer, but no association could be demonstrated with a specific pattern of disease. Furthermore, the CYP1A1 polymorphism was found to be associated with very early emphysema, detectable only by microscope. No association was found between cytochrome P4501A1 and lung cancer, nor with chronic obstructive pulmonary disease. This study demonstrates that the GSTM1 and CYP1A1 polymorphisms have a small, but significant, association with emphysema, which cannot be explained by concomitant lung cancer, since lung cancer alone was not associated with either polymorphism. The association of the polymorphisms with mild emphysema, in particular that seen between CYP1A1 and microscopic emphysema, and not with the severe emphysema represented by chronic obstructive pulmonary disease, and in the case of GSTM1 with autopsy emphysema's, indicates that these enzymes have a general role in the early protection of the lung against damage caused by xenobiotics such as cigarette smoke. Sequencing of the CYP1A1 gene identified a novel polymorphism, a C to A substitution, which results in an amino acid change from threonine to asparagine at position 461 of the gene. Of 26 Scottish individuals previously genotyped as heterozygotes for the Ile-Val462 polymorphism, 14 were subsequently shown to actually have the Thr-Asn461 polymorphism.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available