Modification of the Association Between Frequent Aspirin Use and Ovarian Cancer Risk: A Meta-Analysis Using Individual-Level Data From Two Ovarian Cancer Consortia

Lauren M. Hurwitz, Mary K. Townsend, Susan J. Jordan, Alpa V. Patel, Lauren R. Teras, James V. Lacey, Jennifer A. Doherty, Holly R. Harris, Marc T. Goodman, Yurii B. Shvetsov, Francesmary Modugno, Kirsten B. Moysich, Kim Robien, Anna Prizment, Joellen M. Schildkraut, Andrew Berchuck, Renée T. Fortner, Andrew T. Chan, Nicolas Wentzensen, Patricia HartgeDale P. Sandler, Katie M. O'Brien, Hoda Anton-Culver, Argyrios Ziogas, Usha Menon, Susan J. Ramus, Celeste Leigh Pearce, Anna H. Wu, Emily White, Ulrike Peters, Penelope M. Webb, Shelley S. Tworoger, Britton Trabert

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

PURPOSE Frequent aspirin use has been associated with reduced ovarian cancer risk, but no study has comprehensively assessed for effect modification. We leveraged harmonized, individual-level data from 17 studies to examine the association between frequent aspirin use and ovarian cancer risk, overall and across subgroups of women with other ovarian cancer risk factors.METHODSNine cohort studies from the Ovarian Cancer Cohort Consortium (n = 2,600 cases) and eight case-control studies from the Ovarian Cancer Association Consortium (n = 5,726 cases) were included. We used Cox regression and logistic regression to assess study-specific associations between frequent aspirin use (≥ 6 days/week) and ovarian cancer risk and combined study-specific estimates using random-effects meta-analysis. We conducted analyses within subgroups defined by individual ovarian cancer risk factors (endometriosis, obesity, family history of breast/ovarian cancer, nulliparity, oral contraceptive use, and tubal ligation) and by number of risk factors (0, 1, and ≥ 2).RESULTSOverall, frequent aspirin use was associated with a 13% reduction in ovarian cancer risk (95% CI, 6 to 20), with no significant heterogeneity by study design (P =.48) or histotype (P =.60). Although no association was observed among women with endometriosis, consistent risk reductions were observed among all other subgroups defined by ovarian cancer risk factors (relative risks ranging from 0.79 to 0.93, all P-heterogeneity >.05), including women with ≥ 2 risk factors (relative risk, 0.81; 95% CI, 0.73 to 0.90).CONCLUSIONThis study, the largest to-date on aspirin use and ovarian cancer, provides evidence that frequent aspirin use is associated with lower ovarian cancer risk regardless of the presence of most other ovarian cancer risk factors. Risk reductions were also observed among women with multiple risk factors, providing proof of principle that chemoprevention programs with frequent aspirin use could target higher-risk subgroups.

Original languageEnglish (US)
Pages (from-to)4207-4217
Number of pages11
JournalJournal of Clinical Oncology
Volume40
Issue number36
DOIs
StatePublished - Dec 20 2022

Bibliographical note

Funding Information:
The Australian Ovarian Cancer Study Management Group (D. Bowtell, G. Chenevix-Trench, A. deFazio, D. Gertig, A. Green, and P. Webb) and Australian Cancer Study investigators (A. Green, P. Parsons, N. Hayward, P. Webb, and D. Whiteman) thank all the clinical and scientific collaborators (see http://www.aocstudy.org/ ) and the women 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 Institutes for Health Research Biomedical Research Centre funding scheme. The authors particularly thank I. Jacobs, M. Widschwendter, E. Wozniak, A. Ryan, J. Ford, and N. Balogun for their contribution to the study. Support for title page creation and format was provided by AuthorArranger, a tool developed at the National Cancer Institute. AOCS Study Group members are listed at (online only).

Funding Information:
The authors would like to thank the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, and WY. The authors assume full responsibility for analyses and interpretation of these data. The authors would like to acknowledge the Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, as the home of the Nurses' Health Study. The collection of cancer incidence data used in the California Teachers Study was supported by the California Department of Public Health pursuant to California Health and Safety Code Section 103885; Centers for Disease Control and Prevention's National Program of Cancer Registries, under cooperative agreement 5NU58DP006344; the National Cancer Institute's Surveillance, Epidemiology and End Results Program under contract HHSN261201800032I awarded to the University of California, San Francisco, contract HHSN261201800015I awarded to the University of Southern California, and contract HHSN261201800009I awarded to the Public Health Institute. The opinions, findings, and conclusions expressed herein are those of the author(s) and do not necessarily reflect the official views of the State of California, Department of Public Health, the National Cancer Institute, the National Institutes of Health, the Centers for Disease Control and Prevention or their contractors and subcontractors, or the regents of the University of California, or any of its programs.

Publisher Copyright:
© American Society of Clinical Oncology.

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