Adiposity, Sex Hormones, and Repetitive Element DNA Methylation in Healthy Postmenopausal Women

INTRODUCTION: Low levels of methylation within repetitive DNA elements, such as long interspersed nuclear element-1 (LINE-1) and Alu repeats, are believed to epigenetically predispose an individual to cancer and other diseases. The extent to which lifestyle factors affect the degree of DNA methylation within these genomic regions has yet to be fully understood. Adiposity and sex hormones are established risk factors for certain types of cancer and other illnesses, particularly amongst postmenopausal women. The aim of the current investigation is to assess the impact of adiposity and sex hormones on LINE-1 and Alu methylation in healthy postmenopausal women. METHODS: A cross-sectional study was conducted using baseline data from an ancillary study of the Alberta Physical Activity and Breast Cancer Prevention (ALPHA) Trial. Current adiposity was measured using a dual-energy x-ray absorptiometry (DXA) scan, computed tomography (CT) scan, and balance beam scale. Historical weights were self-reported in a questionnaire. Current endogenous sex hormone concentrations were measured in fasting blood serum. Estimated lifetime number of menstrual cycles was used as a proxy for cumulative exposure to ovarian sex hormones. Repetitive element methylation was quantified in white blood cells using a pyrosequencing assay. Linear regression was used to model the relations of interest while adjusting for important confounders. RESULTS: Adiposity and serum estrogen concentrations were positively related to LINE-1 methylation but were not associated with Alu methylation. Cumulative ovarian sex hormone exposure had a “U-shaped” relation with LINE-1 regardless of folate intake and a negative relation with Alu methylation amongst low folate consumers. Androgens were not associated with repetitive element DNA methylation in this population. CONCLUSION: Adiposity and estrogens appear to play a role in maintaining high levels of repetitive element DNA methylation in healthy postmenopausal women. LINE-1 methylation may be a mechanism whereby estrogen exposure protects against cardiovascular and neurodegenerative illnesses. These results add to the growing body of literature showing how the epigenome is shaped by our lifestyle choices. Future prospective studies assessing the relation between levels of repetitive element DNA methylation in healthy individuals and subsequent disease risk are needed to better understand the clinical significance of these results.

A Study of the Development of the Ability of the Archives Department of the Hudson's Bay Company to Carry Out Document Repairs

The objective of this thesis was to determine whether the establishment and operation of an archives services by the Hudson's Bay Company had an effect on the company's ability to carry out document repairs. Data collection methods included reviews of published material, archival records of the Hudson's Bay Company, and semi-structured interviews. The study found that the Hudson's Bay Company's commitment to operating a modern archives service in accordance with accepted archive administration practices had a substantial effect on its ability to carry out document repairs. The principled approach to repair, as practiced by the Public Record Office, was a major influence. A review of secondary sources placed this development squarely within the context of archival developments in 20th century England. Overall, the thesis findings add to the growing conversation about conservation history in England, in particular, archive conservation history as it occurred outside of the Public Record Office in the 20th century, by discussing how some methods of repair that were devised, adopted and extended by the Public Record Office in the 19th and 20th centuries were adopted and applied in the 20th century by a well-established business corporation.