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Author Notes:

Lauren M. Hurwitz, PhD, MHS, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Dr, Rockville, MD 20850. Email: lauren.hurwitz@nih.gov

Dr Trabert had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: Hurwitz, Berchuck, Anton-Culver, Ziogas, Tworoger, Trabert. Acquisition, analysis, or interpretation of data: Hurwitz, Webb, Jordan, Doherty, Harris, Goodman, Shvetsov, Modugno, Moysich, Schildkraut, Anton-Culver, Ziogas, Menon, Ramus, Wu, Pearce, Wentzensen, Tworoger, Pharoah, Trabert. Drafting of the manuscript: Hurwitz, Ziogas, Trabert. Critical revision of the manuscript for important intellectual content: Webb, Jordan, Doherty, Harris, Goodman, Shvetsov, Modugno, Moysich, Schildkraut, Berchuck, Anton-Culver, Menon, Ramus, Wu, Pearce, Wentzensen, Tworoger, Pharoah, Trabert. Statistical analysis: Hurwitz, Ziogas, Pharoah, Trabert. Obtained funding: Webb, Doherty, Goodman, Modugno, Moysich, Schildkraut, Anton-Culver, Wentzensen. Administrative, technical, or material support: Webb, Modugno, Moysich, Berchuck, Anton-Culver, Ramus, Pearce, Tworoger, Pharoah, Trabert. Supervision: Moysich, Trabert.

The Australian Ovarian Cancer Study investigators thank all of the clinical and scientific collaborators (http://www.aocstudy.org/) and the women who participated in this study for their contribution. Some of this work was undertaken at University College London Hospital/University College London, which received a proportion of funding from the Department of Health’s National Institute for Health Research Biomedical Research Centre funding scheme. Support for title page creation and format was provided by AuthorArranger, a tool developed at the NCI.

Dr Webb reported receiving grants from the US Army Medical Research and Materiel Command, the National Health and Medical Research Council of Australia, the Cancer Foundation of Western Australia, and the Cancer Councils of New South Wales, Victoria, Queensland, South Australia, and Tasmania during the conduct of the study. Dr Webb also reported receiving grants from AstraZeneca outside the submitted work. Dr Jordan reported receiving grants from the National Health and Medical Research Council of Australia, Cancer Australia, and the Medical Research Future Fund outside the submitted work. Dr Modugno reported receiving grants from the National Cancer Institute (NCI) and the US Department of Defense (DoD) during the conduct of the study. Dr Menon reported receiving grants paid to University College London from Cancer Research UK (CRUK), the Medical Research Council, the National Institute for Health and Care Research (NIHR), the India Alliance, and the Eve Appeal during the conduct of the study. In addition, Dr Menon reported receiving funding paid to University College London from the NIHR University College London Hospitals Biomedical Research Centre, iLOF (intelligent Lab on Fiber), RNA Guardian, and Micronoma for research collaboration outside the submitted work. Dr Menon also reported having patent EP10178345.4 licensed to Breast Cancer Diagnostics; holding shares in Abcodia UK (April 1, 2011, to October 30, 2021); and receiving support or honoraria for meetings and travel from the New York Obstetrical Society; Robinson College in Cambridge, UK; and National Cancer Policy Forum in Washington, DC. Dr Menon also reported participating on data safety monitoring or advisory boards for Tina’s Wish, the Mixed COVID Vaccines Study in India, Wellcome Trust DBT in India, and the International Alliance for Cancer Early Detection, Yorkshire Cancer Research, GEM3, NOVEL, CRUK, and PROTECTOR in the UK. Dr Pearce reported receiving grants from the National Institutes of Health (NIH) during the conduct of the study. Dr Tworoger reported receiving grants from the DoD during the conduct of the study as well as outside the submitted work. In addition, Dr Tworoger reported receiving grants from the Florida Department of Health, the NIH, and Bristol-Myers Squibb as well as personal fees from Ponce Health Sciences University, the Ovarian Cancer Research Alliance, NIH, the Roswell Park Comprehensive Cancer Center, and the American Association of Cancer Research outside the submitted work. Dr Tworoger also reported serving as a member of external advisory committees of the University of North Carolina Lineberger Comprehensive Cancer Center, the California Teachers Study (City of Hope), and the Tomorrow Project (Alberta Cancer Center). Dr Pharoah reported receiving grants from CRUK during the conduct of the study. No other disclosures were reported.

Subjects:

Research Funding:

This study was funded by grant W81XWH-19-1-0346 from the DoD Ovarian Cancer Research Program. The Ovarian Cancer Association Consortium was supported by a grant from the Ovarian Cancer Research Fund thanks to donations from the family and friends of Kathryn Sladek Smith. The Australian Ovarian Cancer Study and the Australian Cancer Study were funded by grant DAMD17-01-1-0729 from the US Army Medical Research and Material Command; grants 199600 and 400413 from the National Health and Medical Research Council of Australia; grants from the Cancer Councils of New South Wales, Victoria, Queensland, South Australia, and Tasmania; and grants from the Cancer Foundation of Western Australia. The Diseases of the Ovary and Their Evaluation Study was funded by grants R01 CA112523 and R01 CA87538 from the NCI. The Hawaii Ovarian Cancer Case-Control Study was funded by grants R01 CA58598, N01 CN55424, and N01 PC67001 from the NCI. The Hormones and Ovarian Cancer Prediction Study was funded by grant R01 CA95023 from the NCI and grant DAMD17-02-1-0669 from the DoD. The North Carolina Ovarian Cancer Study was funded by grant R01 CA76016 from the NCI and grant DAMD17-02-1-0666 from the DoD. The University of California, Irvine Ovarian Cancer Study was funded by grants R01 CA58860 and R01 CA92044 from the NCI and grant LVS-39420 from the Lon V Smith Foundation. The UK Ovarian Cancer Population Study was funded by CRUK, the Eve Appeal, and the OAK Foundation. The University of Southern California Study of Lifestyle and Women’s Health was funded by grants R01 CA17054, R01 CA14089, R01 CA61132, N01 PC-67010, and P01 CA17054 from NIH as well as by grants 00-01389V-20170, R03 CA113148, R03 CA115195, and N01 CN25403 from the NIH and grant 2II0200 from the University of Southern California to the California Cancer Research Program. Additional funding was provided by the Huntsman Cancer Institute (Dr Trabert), grant K07-CA80668 from the NCI (Dr Modugno), and grant DGE-2217399-FM from the US National Science Foundation (Dr Modugno).

Keywords:

  • Humans
  • Female
  • Middle Aged
  • Aged
  • Aspirin
  • Genetic Predisposition to Disease
  • Ovarian Neoplasms
  • Carcinoma, Ovarian Epithelial
  • Logistic Models

Association of Frequent Aspirin Use with Ovarian Cancer Risk According to Genetic Susceptibility

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Journal Title:

JAMA Network Open

Volume:

Volume 6, Number 2

Publisher:

, Pages E230666-E230666

Type of Work:

Article | Final Publisher PDF

Abstract:

Importance: Frequent aspirin use is associated with reduced ovarian cancer risk, but it is unknown whether genetic factors modify this association. Understanding effect modifiers is important given that any use of aspirin for ovarian cancer chemoprevention will likely need to focus on specific higher-risk subgroups. Objective: To evaluate whether the association between frequent aspirin use and ovarian cancer is modified by a polygenic score (PGS) for nonmucinous ovarian cancer. Design, Setting, and Participants: We pooled individual-level data from 8 population-based case-control studies from the Ovarian Cancer Association Consortium conducted in the US, UK, and Australia between 1995 and 2009. We included case patients and control participants with both genetic data and data on frequent aspirin use. Case patients with mucinous ovarian cancer were excluded. Data were analyzed between November 1, 2021, and July 31, 2022. Exposures: Frequent aspirin use, defined as daily or almost daily use for 6 months or longer. Main Outcomes and Measures: The main outcome was nonmucinous epithelial ovarian cancer. We used logistic regression to estimate odds ratios (ORs) and 95% CIs and likelihood ratio tests to investigate effect modification by the PGS. Results: There were 4476 case patients with nonmucinous ovarian cancer and 6659 control participants included in this analysis. At study enrollment, the median (IQR) age was 58 (50-66) years for case patients and 57 (49-65) years for control participants. Case patients and control participants self-reported that they were Black (122 [3%] vs 218 [3%]), White (3995 [89%] vs 5851 [88%]), or of other race and ethnicity (348 [8%] vs 580 [9%]; race and ethnicity were unknown for 11 [0%] vs 10 [0%]). There were 575 case patients (13%) and 1030 control participants (15%) who reported frequent aspirin use. The 13% reduction in ovarian cancer risk associated with frequent aspirin use (OR, 0.87 [95% CI, 0.76-0.99]) was not modified by the PGS. Consistent ORs were observed among individuals with a PGS less than (0.85 [0.70-1.02]) and greater than (0.86 [0.74-1.01]) the median. Results were similar by histotype. Conclusions and Relevance: The findings of this study suggest that genetic susceptibility to ovarian cancer based on currently identified common genetic variants does not appear to modify the protective association between frequent aspirin use and ovarian cancer risk. Future work should continue to explore the role of aspirin use for ovarian cancer prevention among individuals who are at higher risk for ovarian cancer..

Copyright information:

2023 Hurwitz LM et al. JAMA Network Open.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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