Molecular mechanisms linking high body mass index to breast cancer etiology in post-menopausal breast tumor and tumor-adjacent tissues

Yujing J. Heng, Jun Wang, Thomas U. Ahearn, Susan B. Brown, Xuehong Zhang, Christine B. Ambrosone, Victor Piana de Andrade, Adam M. Brufsky, Fergus J. Couch, Tari A. King, Francesmary Modugno, Celine M. Vachon, Natalie C. DuPre, Montserrat Garcia-Closas, Melissa A. Troester, David J. Hunter, A. Heather Eliassen, Rulla M. Tamimi, Susan E. Hankinson, Andrew H. Beck

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Purpose: In post-menopausal women, high body mass index (BMI) is an established breast cancer risk factor and is associated with worse breast cancer prognosis. We assessed the associations between BMI and gene expression of both breast tumor and adjacent tissue in estrogen receptor-positive (ER+) and estrogen receptor-negative (ER−) diseases to help elucidate the mechanisms linking obesity with breast cancer biology in 519 post-menopausal women from the Nurses’ Health Study (NHS) and NHSII. Methods: Differential gene expression was analyzed separately in ER+ and ER− disease both comparing overweight (BMI ≥ 25 to < 30) or obese (BMI ≥ 30) women to women with normal BMI (BMI < 25), and per 5 kg/m 2 increase in BMI. Analyses controlled for age and year of diagnosis, physical activity, alcohol consumption, and hormone therapy use. Gene set enrichment analyses were performed and validated among a subset of post-menopausal cases in The Cancer Genome Atlas (for tumor) and Polish Breast Cancer Study (for tumor-adjacent). Results: No gene was differentially expressed by BMI (FDR < 0.05). BMI was significantly associated with increased cellular proliferation pathways, particularly in ER+ tumors, and increased inflammation pathways in ER− tumor and ER− tumor-adjacent tissues (FDR < 0.05). High BMI was associated with upregulation of genes involved in epithelial-mesenchymal transition in ER+ tumor-adjacent tissues. Conclusions: This study provides insights into molecular mechanisms of BMI influencing post-menopausal breast cancer biology. Tumor and tumor-adjacent tissues provide independent information about potential mechanisms.

Original languageEnglish (US)
Pages (from-to)667-677
Number of pages11
JournalBreast Cancer Research and Treatment
Volume173
Issue number3
DOIs
StatePublished - Feb 15 2019

Keywords

  • Breast cancer
  • Gene expression
  • Nurses’ health study
  • Obesity
  • Polish breast cancer study
  • The cancer genome atlas

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Heng, Y. J., Wang, J., Ahearn, T. U., Brown, S. B., Zhang, X., Ambrosone, C. B., de Andrade, V. P., Brufsky, A. M., Couch, F. J., King, T. A., Modugno, F., Vachon, C. M., DuPre, N. C., Garcia-Closas, M., Troester, M. A., Hunter, D. J., Eliassen, A. H., Tamimi, R. M., Hankinson, S. E., & Beck, A. H. (2019). Molecular mechanisms linking high body mass index to breast cancer etiology in post-menopausal breast tumor and tumor-adjacent tissues. Breast Cancer Research and Treatment, 173(3), 667-677. https://doi.org/10.1007/s10549-018-5034-1