Globalisation has resulted in several anthropometric, reproductive, and lifestyle factors and/or exposures exhibiting secular trends. These same factors and exposures have been implicated in modifying breast cancer risk and have been shown to influence DNA methylation in at least one publication. In this thesis, I conduct a preliminary and exploratory investigation to examine whether socioeconomic status, nutritional factors, weight and height, age at menarche, menopausal status, age at menopause, and estimated lifetime estrogen exposure (ELEE) – all factors displaying secular trends and influencing breast cancer risk – are associated with DNA methylation.
The LUminometric Methylation Assay (LUMA) was used to assess global methylation in 376 female subjects from the EPIC cohort and the Infinium HumanMethylation 450 BeadChip, was used to assess genome-wide methylation in 667 male and female subjects from the EPIC Italy subcohort. Genome wide, probe-type specific, CpG locus specific, clustering and single enrichment analyses were performed.
Total caloric intake, folate intake, total dietary methyl intake, and age at menarche were found to be associated with global methylation using LUMA. In addition, the 450k BeadChip results suggest that education, household density, highest household occupational position, total caloric intake, folate intake, dietary methyl intake, adherence to the Italian Mediterranean diet, body mass index, age at menopause and ELEE influence methylation patterns, but the power of these investigations did not permit identification of biologically relevant, differentially methylated CpG sites.
The present findings indicate that DNA methylation may be one way through which these exposures may become biologically embedded and influence disease risk, and especially breast cancer risk. Mechanisms involving epigenetic changes provide a possible mechanism though which even early life exposures can affect adult disease risk. However, more detailed and more powered epidemiological study designs and tools need to be implemented in order to confirm these associations and also examine causality.