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Title: DNA methylation in breast cancer and the effect of diet and lifestyle
Author: Scott, Paula
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2015
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There is accumulating evidence that several diet and lifestyle factors affect breast cancer risk. One of the proposed mechanisms behind this is DNA methylation which has been observed in breast cancer, even in the very early stages, and may be altered in response to these risk factors. There is also growing interest in the detection of aberrant DNA methylation in non-tumour cells which could be utilised for breast cancer screening. The main questions addressed were: whether B vitamin intake and lifestyle factors were associated with breast cancer risk and DNA methylation and whether DNA methylation within whole blood or buccal cell DNA was associated with breast cancer risk. Samples were obtained from controls and women newly diagnosed with breast cancer and Pyrosequencingâ„¢ technology was used to analyse the percentage methylation of LINE-1, BRCA1, ER , p16, MGMT, RAR 2, RASSF1A, and ALDH2 in both sample types. Information on B vitamin intake, alcohol, smoking, physical activity, and reproductive factors was obtained via questionnaire Hypermethylation of ER was associated with a decreased risk of breast cancer and a positive correlation was observed between methylation of ER and BRCA1. After adjustment for ER methylation, results suggested that BRCA1 hypermethylation was associated with an increased breast cancer risk. This provides support for extension of 'field effect' concept and the utility of non-tumour cells in breast cancer screening. Associations were observed between B vitamin intake, lifestyle and both breast cancer risk and DNA methylation. Smoking was associated with an increased risk of premenopausal breast cancer, hypermethylation of BRCA1, and hypomethylation of LINE-1 but in postmenopausal women, results suggest a decreased risk and hypomethylation of p16. Alcohol was associated with an increased risk of breast cancer, hypomethylation of BRCA1, and hypermethylation of p16 in women with the lowest folate intakes but not in those consuming higher amounts.
Supervisor: Not available Sponsor: Fraserburgh Moonlight Prowl (Breast Cancer Campaign)
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Breast ; DNA ; Diet ; Health behavior