Throughout life, methylation of DNA plays an important role in normal and appropriate regulation of gene expression. Many gene-specific changes in methylation have been described in the context of disease predisposition, development and progression, including cancer. However, the literature for breast cancer is still sparse.The hypothesis of this research proposal is that aberrant methylation of DNA in some genes plays an important role in breast carcinogenesis and progression. Specifically, the hypotheses are that (i) measures of methylation of DNA from peripheral blood and saliva are associated with breast cancer risk; (ii) measures of methylation of DNA from breast tumours are important prognostic indicators.The plan to test these hypotheses is to conduct a case-control study on breast cancer nested within the E3N French cohort. Methylation levels in DNA extracted from blood collected before diagnosis will be measured in a panel of CpG loci potentially involved in breast carcinogenesis and in the DNA repetitive elements LINE-1 and Alu. Then, the risk of breast cancer in relation with their pre-diagnostic methylation levels will be estimated. Tumour tissues will be retrieved for breast cancer cases and methylation levels in DNA extracted from tumour will be measured in a panel of CpG loci potentially involved in breast cancer progression. The correlation of the methylation levels with the clinico-pathological breast cancer prognostic factors and survival will be estimated. To verify that the association between methylation levels and breast cancer risk is mediated by the regulation of gene expression, gene expression in the tumour samples will be measured and correlated with methylation levels.This study will further our understanding of the biology of breast cancer and its findings could open new avenues for the prevention, early detection and treatment of breast cancer.