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dc.contributor.advisorWalker, Logan
dc.contributor.advisorCurrie, Margaret
dc.contributor.advisorPhillips, Elisabeth
dc.contributor.authorCrake, Rebekah Lee Isla
dc.date.available2015-11-10T22:19:54Z
dc.date.copyright2015
dc.identifier.citationCrake, R. L. I. (2015). Exploring Molecular Links between Obesity and Breast Cancer (Thesis, Bachelor of Biomedical Sciences with Honours). University of Otago. Retrieved from http://hdl.handle.net/10523/6057en
dc.identifier.urihttp://hdl.handle.net/10523/6057
dc.description.abstractObesity is associated with a high risk of incidence of, and mortality for, postmenopausal breast cancer. Despite this well-established link, the molecular and mechanistic basis of the obesity and breast cancer association still remains unclear. In obesity research, genetic variation due to copy number differences has become increasingly popular. The salivary amylase gene, AMY1, is well-known for its extensive copy number variation (CNV) in the human genome and has previously been correlated with a genetic predisposition toward obesity; however, research surrounding this association is controversial. Despite an established relationship between obesity and breast cancer risk, the recently reported genetic association between AMY1 CNV and obesity has not yet been examined in normal and obese breast cancer patients. Furthermore, gene expression changes in breast tumours from obese women remain poorly characterised. We hypothesise that obese breast cancer patients are associated with (1) low AMY1 copy number and (2) differential expression of candidate genes in the breast tumour. This study included 55 post-menopausal breast cancer patients from The Cancer Society Tissue Bank, with a BMI (body mass index)> 30 (obese; n=28) or BMI < 25 (healthy; n=27). Quantitative PCR (qPCR) assessment of germline AMY1 copy number status from blood showed that obese breast cancer patients have a lower average copy number of AMY1 compared to normal weight patients. Examining breast tumour expression profiles of obese and non-obese patients from two published studies, identified four candidate genes (GRIA2, DUSP4, NR2F1, and ADH1B) shared between both studies. Analysis of gene expression data from The Cancer Genome Atlas (TCGA) indicated that these four genes are differentially expressed within clinically relevant breast tumour subtypes characterised by oestrogen receptor, progesterone receptor and HER2 status. qPCR analysis of each candidate gene within our study cohort showed that the average expression of GRIA2, DUSP4, NR2F1 and ADH1B was lower in obese compared to healthy breast tumours, but these results were not statistically significant. My study indicated that BMI may be associated with lower germline copy number of AMY1 in post-menopausal breast cancer patients; however, further work with a larger cohort is needed to establish if GRIA2, DUSP4, NR2F1 and ADH1B are associated with obesity related breast cancer.
dc.format.mimetypeapplication/pdf
dc.language.isoen
dc.publisherUniversity of Otago
dc.rightsAll items in OUR Archive are provided for private study and research purposes and are protected by copyright with all rights reserved unless otherwise indicated.
dc.subjectObesity
dc.subjectBreast Cancer
dc.subjectGenetics
dc.subjectAMY1
dc.subjectDUSP4
dc.subjectGRIA2
dc.subjectNR2F1
dc.subjectADH1B
dc.subjectMolecular
dc.subjectBMI
dc.subjectbody mass index
dc.subjectCNV
dc.subjectcopy number variation
dc.subjectamylase
dc.subjectexpression
dc.titleExploring Molecular Links between Obesity and Breast Cancer
dc.typeThesis
dc.date.updated2015-11-10T21:21:51Z
dc.language.rfc3066en
thesis.degree.disciplinePathology
thesis.degree.nameBachelor of Biomedical Sciences with Honours
thesis.degree.grantorUniversity of Otago
thesis.degree.levelHonours
otago.openaccessOpen
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