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Title: The pharmacogenetics of breast cancer treatment
Author: Abraham, J. E.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2011
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The core project in this thesis is the translational study PGSNPS, which aimed to investigate the pharmacogenetics of breast cancer chemotherapy in the adjuvant setting. Blood or saliva samples were collected from over 2300 patients, who were recruited during a 4 year period. The trial design was adapted to a GWAS approach. The combination of high quality genotype data and detailed clinical information allows this collection to be a useful resource not only for pharmacogenetic analysis but for investigation of prognosis and susceptibility in future analyses. I also examined the role of candidate gene analysis in the identification of variants associated with survival and susceptibility analysis. Candidate gene analysis of the prostaglandin pathway investigated the potential role of key genes in this pathway and their association with breast cancer susceptibility and survival. There was little evidence that common variants are associated with modest risks of breast cancers and no evidence for association with overall survival (OS) for any tagSNP studied. The metabolic enzyme cytochrome P450 2D6, (CYP2D6), is involved in the metabolism of tamoxifen to its active metabolites. I examined the role of the CYP2D6 gene in breast cancer specific survival (BCSS) and OS in tamoxifen treated breast cancer patients. One putative poor metaboliser (PM) CYP2D6*6 may be associated with decreased BCSS and OS, but the prior probability of such an association is low. All other putative functional variants showed no association. The evidence from this study does not support implementation of routine CYP2D6 testing pre-treatment to guide choice of hormone therapy.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available