AIM 2

AIM II – Study gene expression in peripheral blood cells
The main hypothesis is that breast cancer, even during early stages, affects the biochemical environment of peripheral blood cells and causes systematic changes in the mRNA expression pattern (the transcriptome) of certain genes. By analysing the expression pattern of these genes, it may be possible to discriminate between breast cancer and non-breast cancer samples. To be able to perform such expression analyses high quality mRNA is needed. These analyses will enable us to set the stage for the future analyses of comparing the genome wide expression profile at the time of diagnosis with the expression profile at a healthy stage in order to detect profiles that are specific for individuals that have developed a malignant disease. Genes that are altered in their expression in PBCs at the disease stage may have become altered as a response to tumor development at an early stage. Breast cancer case should be compared to healthy subjects in order to look at mRNA changes over time in a prospective design. Thus, from these analyses we hope to be able to find expression profiles of subset of genes that predict breast cancer that can further be evaluated as early diagnostic markers. This part of the study will have to await notification of incident cases of cancer among the cohort members.
A first approach to the possible carcinogenic effect of HRT will be the expression analysis of mRNA in a cross-sectional study to compare 50 users with 50 non-users of HRT from NOWAC. The biochemical work finished medio 2004. The statistical analyses will be done by our statistician in collaboration with research groups in Oslo. We will also explore the possibility of using expression analysis as a marker of exposure, as shown for smoking.