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). METHODS: We analyzed gene expression profiles from 311 normal breast tissue biopsies from cancer‐free, post‐menopausal women, using Illumina bead chip arrays. Principal component analysis and K‐means clustering was used for initial analysis of the dataset. The association of exposures and covariates with gene expression was determined using linear models for microarrays. RESULTS: Heterogeneity of the breast tissue and cell composition had the strongest influence on gene expression profiles. After adjusting for cell composition, obesity, smoking, and alcohol showed the highest numbers of associated genes and pathways, whereas hormone therapy and parity were associated with negligible gene expression differences. CONCLUSION: Our results provide insight into associations between major exposures and gene expression profiles and provide an informative baseline for improved understanding of exposure‐related molecular events in normal breast tissue of cancer‐free, post‐menopausal women.