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Associations between prediagnostic aspirin use and ovarian tumor gene expression.

Publication ,  Journal Article
Sasamoto, N; Stewart, PA; Wang, T; Thompson, ZJ; Yoder, SJ; Hecht, JL; Cleveland, JL; Conejo-Garcia, J; Fridley, BL; Terry, KL; Tworoger, SS
Published in: Cancer Med
September 2023

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 <1.5 × 10-4 ) and downregulation of multiple extracellular matrix (ECM) architecture pathways (e.g., ECM organization, 4.7 × 10-8 ). CONCLUSION: Our results suggest low and regular-dose aspirin may impair ovarian tumorigenesis in part via enhancing adaptive immune response and decreasing metastatic potential supporting the likely differential effects on ovarian carcinogenesis and progression by dose of aspirin.

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Published In

Cancer Med

DOI

EISSN

2045-7634

Publication Date

September 2023

Volume

12

Issue

17

Start / End Page

18405 / 18417

Location

United States

Related Subject Headings

  • Ovarian Neoplasms
  • Humans
  • Gene Expression
  • Female
  • Estrogens
  • Case-Control Studies
  • Aspirin
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 0601 Biochemistry and Cell Biology
 

Citation

APA
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ICMJE
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Sasamoto, N., Stewart, P. A., Wang, T., Thompson, Z. J., Yoder, S. J., Hecht, J. L., … Tworoger, S. S. (2023). Associations between prediagnostic aspirin use and ovarian tumor gene expression. Cancer Med, 12(17), 18405–18417. https://doi.org/10.1002/cam4.6386
Sasamoto, Naoko, Paul A. Stewart, Tianyi Wang, Zachary J. Thompson, Sean J. Yoder, Jonathan L. Hecht, John L. Cleveland, et al. “Associations between prediagnostic aspirin use and ovarian tumor gene expression.Cancer Med 12, no. 17 (September 2023): 18405–17. https://doi.org/10.1002/cam4.6386.
Sasamoto N, Stewart PA, Wang T, Thompson ZJ, Yoder SJ, Hecht JL, et al. Associations between prediagnostic aspirin use and ovarian tumor gene expression. Cancer Med. 2023 Sep;12(17):18405–17.
Sasamoto, Naoko, et al. “Associations between prediagnostic aspirin use and ovarian tumor gene expression.Cancer Med, vol. 12, no. 17, Sept. 2023, pp. 18405–17. Pubmed, doi:10.1002/cam4.6386.
Sasamoto N, Stewart PA, Wang T, Thompson ZJ, Yoder SJ, Hecht JL, Cleveland JL, Conejo-Garcia J, Fridley BL, Terry KL, Tworoger SS. Associations between prediagnostic aspirin use and ovarian tumor gene expression. Cancer Med. 2023 Sep;12(17):18405–18417.
Journal cover image

Published In

Cancer Med

DOI

EISSN

2045-7634

Publication Date

September 2023

Volume

12

Issue

17

Start / End Page

18405 / 18417

Location

United States

Related Subject Headings

  • Ovarian Neoplasms
  • Humans
  • Gene Expression
  • Female
  • Estrogens
  • Case-Control Studies
  • Aspirin
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 0601 Biochemistry and Cell Biology