학술논문
Psychosocial stressors and breast cancer gene expression in the Black Women's Health Study.
Document Type
Academic Journal
Author
Barnard ME; Slone Epidemiology Center, Boston University Chobanian & Avedisian School of Medicine, 72 E. Concord St., Boston, MA, 02118, USA.; Wang X; Division of Computational Biomedicine, Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.; Department of Biostatistics, Boston University, Boston, MA, USA.; Petrick JL; Slone Epidemiology Center, Boston University Chobanian & Avedisian School of Medicine, 72 E. Concord St., Boston, MA, 02118, USA.; Zirpoli GR; Slone Epidemiology Center, Boston University Chobanian & Avedisian School of Medicine, 72 E. Concord St., Boston, MA, 02118, USA.; Jones D; Department of Pathology and Laboratory Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.; Johnson WE; Division of Computational Biomedicine, Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.; Division of Infectious Disease, Center for Data Science, Rutgers New Jersey Medical School, Newark, NJ, USA.; Palmer JR; Slone Epidemiology Center, Boston University Chobanian & Avedisian School of Medicine, 72 E. Concord St., Boston, MA, 02118, USA. jpalmer@bu.edu.
Source
Publisher: Kluwer Academic Country of Publication: Netherlands NLM ID: 8111104 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-7217 (Electronic) Linking ISSN: 01676806 NLM ISO Abbreviation: Breast Cancer Res Treat Subsets: MEDLINE
Subject
Language
English
Abstract
Purpose: Prior studies indicate that the physiologic response to stress can affect gene expression. We evaluated differential gene expression in breast cancers collected from Black women with high versus low exposure to psychosocial stressors.
Methods: We analyzed tumor RNA sequencing data from 417 Black Women's Health Study breast cancer cases with data on early life trauma and neighborhood disadvantage. We conducted age-adjusted differential gene expression analyses and pathway analyses. We also evaluated Conserved Transcriptional Response to Adversity (CTRA) contrast scores, relative fractions of immune cell types, T cell exhaustion, and adrenergic signaling. Analyses were run separately for estrogen receptor positive (ER+; n = 299) and ER- (n = 118) cases.
Results: Among ER+ cases, the top differentially expressed pathways by stress exposure were related to RNA and protein metabolism. Among ER- cases, they were related to developmental biology, signal transduction, metabolism, and the immune system. Targeted analyses indicated greater immune pathway enrichment with stress exposure for ER- cases, and possible relevance of adrenergic signaling for ER+ cases. CTRA contrast scores did not differ by stress exposure, but in analyses of the CTRA components, ER- breast cancer cases with high neighborhood disadvantage had higher pro-inflammatory gene expression (p = 0.039) and higher antibody gene expression (p = 0.006) compared to those with low neighborhood disadvantage.
Conclusion: There are multiple pathways through which psychosocial stress exposure may influence breast tumor biology. Given the present findings on inflammation and immune response in ER- tumors, further research to identify stress-induced changes in the etiology and progression of ER- breast cancer is warranted.
(© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Methods: We analyzed tumor RNA sequencing data from 417 Black Women's Health Study breast cancer cases with data on early life trauma and neighborhood disadvantage. We conducted age-adjusted differential gene expression analyses and pathway analyses. We also evaluated Conserved Transcriptional Response to Adversity (CTRA) contrast scores, relative fractions of immune cell types, T cell exhaustion, and adrenergic signaling. Analyses were run separately for estrogen receptor positive (ER+; n = 299) and ER- (n = 118) cases.
Results: Among ER+ cases, the top differentially expressed pathways by stress exposure were related to RNA and protein metabolism. Among ER- cases, they were related to developmental biology, signal transduction, metabolism, and the immune system. Targeted analyses indicated greater immune pathway enrichment with stress exposure for ER- cases, and possible relevance of adrenergic signaling for ER+ cases. CTRA contrast scores did not differ by stress exposure, but in analyses of the CTRA components, ER- breast cancer cases with high neighborhood disadvantage had higher pro-inflammatory gene expression (p = 0.039) and higher antibody gene expression (p = 0.006) compared to those with low neighborhood disadvantage.
Conclusion: There are multiple pathways through which psychosocial stress exposure may influence breast tumor biology. Given the present findings on inflammation and immune response in ER- tumors, further research to identify stress-induced changes in the etiology and progression of ER- breast cancer is warranted.
(© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)