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

Author:

Krum‐Hansen Sanda12ORCID,Standahl Olsen Karina1,Anderssen Endre3,Frantzen Jan Ole4,Lund Eiliv1,Paulssen Ruth H.35

Affiliation:

1. Department of Community Medicine UiT The Arctic University of Norway Tromsø Norway

2. Department of Hematology and Oncology Stavanger University Hospital Stavanger Norway

3. Genomics Support Center Tromsø (GSCT) UiT The Arctic University of Norway Tromsø Norway

4. Narvik Hospital University Hospital of North Norway Narvik Norway

5. Department of Clinical Medicine UiT The Arctic University of Norway Tromsø Norway

Abstract

AbstractBackgroundNormal 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).MethodsWe 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.ResultsHeterogeneity 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.ConclusionOur 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.

Funder

Helse Nord RHF

Publisher

Wiley

Subject

Cancer Research,Oncology

Reference70 articles.

1. WHO.Global Cancer Observatory 2022.https://gco.iarc.fr/.

2. WHO.Breast Cancer Fact Sheet 2022.https://www.who.int/news-room/fact-sheets/detail/breast-cancer.

3. WCRF.Diet and Cancer Report 2022.www.wcrf.org/dietandcancer/contents.

4. Comparison of Breast Cancer to Healthy Control Tissue Discovers Novel Markers with Potential for Prognosis and Early Detection

5. Gene expression in histologically normal epithelium from breast cancer patients and from cancer-free prophylactic mastectomy patients shares a similar profile

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