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

Author:

Hurwitz Lauren M.1ORCID,Townsend Mary K.2ORCID,Jordan Susan J.3ORCID,Patel Alpa V.4,Teras Lauren R.4ORCID,Lacey James V.5,Doherty Jennifer A.6ORCID,Harris Holly R.7ORCID,Goodman Marc T.8,Shvetsov Yurii B.9ORCID,Modugno Francesmary1011,Moysich Kirsten B.12ORCID,Robien Kim13ORCID,Prizment Anna14,Schildkraut Joellen M.15,Berchuck Andrew16,Fortner Renée T.17ORCID,Chan Andrew T.1819ORCID,Wentzensen Nicolas1ORCID,Hartge Patricia1,Sandler Dale P.20ORCID,O'Brien Katie M.20ORCID,Anton-Culver Hoda21ORCID,Ziogas Argyrios21ORCID,Menon Usha22ORCID,Ramus Susan J.2324ORCID,Pearce Celeste Leigh25ORCID,Wu Anna H.26ORCID,White Emily27,Peters Ulrike27,Webb Penelope M.28ORCID,Tworoger Shelley S.2ORCID,Trabert Britton129ORCID

Affiliation:

1. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD

2. Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL

3. School of Public Health, University of Queensland, Brisbane, Queensland, Australia

4. Department of Population Science, American Cancer Society, Atlanta, GA

5. Department of Computational and Quantitative Medicine, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA

6. Department of Population Health Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT

7. Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA

8. Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA

9. Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI

10. Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, PA

11. Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA

12. Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY

13. Department of Exercise and Nutrition Sciences, Milken Institute School of Public Health, George Washington University, Washington, DC

14. Division of Hematology, Oncology and Transplantation, University of Minnesota Masonic Cancer Center, University of Minnesota, Minneapolis, MN

15. Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA

16. Division of Gynecologic Oncology, Duke University Medical Center, Durham, NC

17. Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany

18. Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, MA

19. Division of Gastroenterology, Massachusetts General Hospital, Boston, MA

20. Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC

21. Department of Epidemiology, University of California Irvine, Irvine, CA

22. MRC Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London, London, UK

23. School of Women's and Children's Health, Faculty of Medicine, University of NSW Sydney, Sydney, Australia

24. Adult Cancer Program, Lowy Cancer Research Centre, University of NSW Sydney, Sydney, Australia

25. Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI

26. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA

27. Cancer Prevention Program, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA

28. Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia

29. Department of Obstetrics and Gynecology, University of Utah, Huntsman Cancer Institute, Salt Lake City, UT

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. METHODS Nine 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). RESULTS Overall, 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). CONCLUSION This 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.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

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