Associations of breast cancer related exposures and gene expression profiles in normal breast tissue-The Norwegian Women and Cancer normal breast tissue study.

Background: Normal breast tissue is utilized in tissue-based studies of breast carcinogenesis. While gene expression in breast tumor tissue is well explored, our knowledge of transcriptomic signatures in normal breast tissue is still incomplete. The aim of this study was to investigate variability of gene expression in a large sample of normal breast tissue biopsies, according to breast cancer related exposures (obesity, smoking, alcohol, hormone therapy, and parity).

Interactions between the tumor and the blood systemic response of breast cancer patients.

Although systemic immunity is critical to the process of tumor rejection, cancer research has largely focused on immune cells in the tumor microenvironment. To understand molecular changes in the patient systemic response (SR) to the presence of BC, we profiled RNA in blood and matched tumor from 173 patients. We designed a system (MIxT, Matched Interactions Across Tissues) to systematically explore and link molecular processes expressed in each tissue.

Peripheral blood cells inform on the presence of breast cancer: a population-based case-control study.

Tumor-host interactions extend beyond the local microenvironment and cancer development largely depends on the ability of malignant cells to hijack and exploit the normal physiological processes of the host. Here, we established that many genes within peripheral blood cells show differential expression when an untreated breast cancer (BC) is present, and harnessed this fact to construct a 50-gene signature that distinguish BC patients from population-based controls. Our results were derived from a series of large datasets within our unique population-based Norwegian Women and Cancer cohort that allowed us to investigate the influence of medications and tumor characteristics on our blood-based test, and were further tested in two external datasets.

Gene expression profiles of breast biopsies from healthy women identify a group with claudin-low features.

Background: Increased understanding of the variability in normal breast biology will enable us to identify mechanisms of breast cancer initiation and the origin of different subtypes, and to better predict breast cancer risk.

Methods: Gene expression patterns in breast biopsies from 79 healthy women referred to breast diagnostic centers in Norway were explored by unsupervised hierarchical clustering and supervised analyses, such as gene set enrichment analysis and gene ontology analysis and comparison with previously published genelists and independent datasets.

Results: Unsupervised hierarchical clustering identified two separate clusters of normal breast tissue based on gene-expression profiling, regardless of clustering algorithm and gene filtering used.

Expression levels of uridine 5'-diphospho-glucuronosyltransferase genes in breast tissue from healthy women are associated with mammographic density.

Introduction: Mammographic density (MD), as assessed from film screen mammograms, is determined by the relative content of adipose, connective and epithelial tissue in the female breast. In epidemiological studies, a high percentage of MD confers a four to six fold risk elevation of developing breast cancer, even after adjustment for other known breast cancer risk factors. However, the biologic correlates of density are little known.

Gene expression analyses in breast cancer epidemiology: the Norwegian Women and Cancer postgenome cohort study.

Introduction: The introduction of high-throughput technologies, also called -omics technologies, into epidemiology has raised the need for high-quality observational studies to reduce several sources of error and bias.

Methods: The Norwegian Women and Cancer (NOWAC) postgenome cohort study consists of approximately 50,000 women born between 1943 and 1957 who gave blood samples between 2003 and 2006 and filled out a two-page questionnaire. Blood was collected in such a way that RNA is preserved and can be used for gene expression analyses.