Associations between prediagnostic aspirin use and ovarian tumor gene expression

Autor: Naoko Sasamoto, Paul A. Stewart, Tianyi Wang, Zachary J. Thompson, Sean J. Yoder, Jonathan L. Hecht, John L. Cleveland, Jose Conejo‐Garcia, Brooke L. Fridley, Kathryn L. Terry, Shelley S. Tworoger
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Cancer Medicine, Vol 12, Iss 17, Pp 18405-18417 (2023)
Druh dokumentu: article
ISSN: 2045-7634
DOI: 10.1002/cam4.6386
Popis: Abstract Background Aspirin use has been associated with reduced ovarian cancer risk, yet the underlying biological mechanisms are not fully understood. To gain mechanistic insights, we assessed the association between prediagnosis low and regular‐dose aspirin use and gene expression profiles in ovarian tumors. Methods RNA sequencing was performed on high‐grade serous, poorly differentiated, and high‐grade endometrioid ovarian cancer tumors from the Nurses' Health Study (NHS), NHSII, and New England Case–Control Study (n = 92 cases for low, 153 cases for regular‐dose aspirin). Linear regression identified differentially expressed genes associated with aspirin use, adjusted for birth decade and cohort. False discovery rates (FDR) were used to account for multiple testing and gene set enrichment analysis was used to identify biological pathways. Results No individual genes were significantly differentially expressed in ovarian tumors in low or regular‐dose aspirin users accounting for multiple comparisons. However, current versus never use of low‐dose aspirin was associated with upregulation of immune pathways (e.g., allograft rejection, FDR = 5.8 × 10−10; interferon‐gamma response, FDR = 2.0 × 10−4) and downregulation of estrogen response pathways (e.g., estrogen response late, FDR = 4.9 × 10−8). Ovarian tumors from current regular aspirin users versus never users were also associated with upregulation in interferon pathways (FDR
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