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Lifetime ovulatory years and ovarian cancer gene expression profiles.
Sasamoto, Naoko; Stewart, Paul A; Wang, Tianyi; Yoder, Sean J; Chellappan, Srikumar; Hecht, Jonathan L; Fridley, Brooke L; Terry, Kathryn L; Tworoger, Shelley S.
Afiliação
  • Sasamoto N; Department of Obstetrics and Gynecology, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Avenue, Boston, MA, 02115, USA. nsasamoto@bwh.harvard.edu.
  • Stewart PA; Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
  • Wang T; Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
  • Yoder SJ; Molecular Genomics Core, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
  • Chellappan S; Department of Tumor Biology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
  • Hecht JL; Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
  • Fridley BL; Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
  • Terry KL; Department of Obstetrics and Gynecology, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Avenue, Boston, MA, 02115, USA.
  • Tworoger SS; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
J Ovarian Res ; 15(1): 59, 2022 May 13.
Article em En | MEDLINE | ID: mdl-35562768
ABSTRACT

BACKGROUND:

Greater ovulatory years is associated with increased ovarian cancer risk. Although ovulation leads to an acute pro-inflammatory local environment, how long-term exposure to ovulation impacts ovarian carcinogenesis is not fully understood. Thus, we examined the association between gene expression profiles of ovarian tumors and lifetime ovulatory years to enhance understanding of associated biological pathways.

METHODS:

RNA sequencing data was generated on 234 invasive ovarian cancer tumors that were high-grade serous, poorly differentiated, or high-grade endometrioid from the Nurses' Health Study (NHS), NHSII, and the New England Case Control Study. We used linear regression to identify differentially expressed genes by estimated ovulatory years, adjusted for birth decade and cohort, overall and stratified by menopausal status at diagnosis. We used false discovery rates (FDR) to account for multiple testing. Gene set enrichment analysis (GSEA) with Cancer Hallmarks, KEGG, and Reactome databases was used to identify biological pathways associated with ovulatory years.

RESULTS:

No individual genes were significantly differentially expressed by ovulatory years (FDR > 0.19). However, GSEA identified several pathways that were significantly associated with ovulatory years, including downregulation of pathways related to inflammation and proliferation (FDR < 1.0 × 10-5). Greater ovulatory years were more strongly associated with downregulation of genes related to proliferation (e.g., E2F targets, FDR = 1.53 × 10-24; G2M checkpoints, FDR = 3.50 × 10-22) among premenopausal versus postmenopausal women at diagnosis. The association of greater ovulatory years with downregulation of genes involved in inflammatory response such as interferon gamma response pathways (FDR = 7.81 × 10-17) was stronger in postmenopausal women.

CONCLUSIONS:

Our results provide novel insight into the biological pathways that link ovulatory years to ovarian carcinogenesis, which may lead to development of targeted prevention strategies for ovarian cancer.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Transcriptoma Tipo de estudo: Observational_studies / Risk_factors_studies Limite: Female / Humans Idioma: En Revista: J Ovarian Res Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Transcriptoma Tipo de estudo: Observational_studies / Risk_factors_studies Limite: Female / Humans Idioma: En Revista: J Ovarian Res Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos