Breast cancer is the most common type of female cancer in the UK and the second most common cause of cancer death. Many factors, including genetic and environmental influences, contribute to an individual's lifetime risk. The role of epigenetics, particularly DNA methylation, has been considered as a mechanism that could link these risks and provide a non-genetic explanation of cancer heritability. Loss of imprinting is a hallmark of many cancers and has been observed in non-tumour tissue of affected and at risk individuals. Many imprinted genes maintain their allele specific methylation in a wide range of adult somatic tissues, remaining stable throughout life. Repeat elements are also of interest as they have been implicated in imprint maintenance. The main hypothesis of this study was that altered DNA methylation at imprinted gene regions would be observed in blood samples of breast cancer patients, when compared to a matched disease-free population. Methylation levels of imprinted gene regions and repeat elements were examined for breast cancer risk and associated clinical and pathological characteristics, within a case-control cohort. Genotypes within the 11p15 imprint cluster (a region which presents loss of imprinting in cancer) were examined and interactions with epigenotype considered. DNA methylation changes were observed in non-tumour tissue in women with breast cancer at imprinted genes PEG3, INPP5F, KCNQ1OT1, KvDMR, L3MBTL and PLAGL1/ZAC1. Methylation changes were identified which have the potential to differentiate between patients who may or may not progress onto invasive breast cancer. Pathological characteristics of breast cancer were also linked to DNA methylation changes which could enhance our knowledge of tumour heterogeneity. Genotype-epigenotype interactions were observed within the 11p15 region and two genetic variants were associated with breast cancer risk. Results reported here enhance our current knowledge of methylation changes in blood of breast cancer patients and could contribute to the development of screening approaches and personalised treatments.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:668969 |
| Date | January 2015 |
| Creators | Harrison, Kristina |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=227583 |
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