The Risk of Ovarian Cancer Increases with an Increase in the Lifetime Number of Ovulatory Cycles: An Analysis from the Ovarian Cancer Cohort Consortium (OC3)
Abstract
Repeated exposure to the acute proinflammatory environment that follows ovulation at the ovarian surface and distal fallopian tube over a woman's reproductive years may increase ovarian cancer risk. To address this, analyses included individual-level data from 558,709 naturally menopausal women across 20 prospective cohorts, among whom 3,246 developed invasive epithelial ovarian cancer (2,045 serous, 319 endometrioid, 184 mucinous, 121 clear cell, 577 other/unknown). Cox models were used to estimate multivariable-adjusted HRs between lifetime ovulatory cycles (LOC) and its components and ovarian cancer risk overall and by histotype. Women in the 90th percentile of LOC (>514 cycles) were almost twice as likely to be diagnosed with ovarian cancer than women in the 10th percentile (<294) [HR (95% confidence interval): 1.92 (1.60–2.30)]. Risk increased 14% per 5-year increase in LOC (60 cycles) [(1.10–1.17)]; this association remained after adjustment for LOC components: number of pregnancies and oral contraceptive use [1.08 (1.04–1.12)]. The association varied by histotype, with increased risk of serous [1.13 (1.09–1.17)], endometrioid [1.20 (1.10–1.32)], and clear cell [1.37 (1.18–1.58)], but not mucinous [0.99 (0.88–1.10), P-heterogeneity = 0.01] tumors. Heterogeneity across histotypes was reduced [P-heterogeneity = 0.15] with adjustment for LOC components [1.08 serous, 1.11 endometrioid, 1.26 clear cell, 0.94 mucinous]. Although the 10-year absolute risk of ovarian cancer is small, it roughly doubles as the number of LOC rises from approximately 300 to 500. The consistency and linearity of effects strongly support the hypothesis that each ovulation leads to small increases in the risk of most ovarian cancers, a risk that cumulates through life, suggesting this as an important area for identifying intervention strategies.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Mar 01, 2020
- Source ID
- 10.1158/0008-5472.can-19-2850
Entities
People
- Alan A Arslan
- Alicja Wolk
- Alpa V. Patel
- Anne Zeleniuch-jacquotte
- Annika Idahl
- Anthony Swerdlow
- Antonia Trichopoulou
- Britton Trabert
- Catherine Schairer
- Dale Sandler
- Edwin S. Iversen
- Elio Riboli
- Emily White
- Gary E. Fraser
- Graham Giles
- Holly R Harris
- I-min Lee
- Inger T Gram
- James V. Lacey
- Jenny N. Poynter
- Judith Hoffman Bolton
- Julie E. Buring
- Kala Visvanathan
- Katie O'Brien
- Kim Overvad
- Kim Robien
- Laure Dossus
- Leo J Schouten
- Leslie Bernstein
- Louise A. Brinton
- Lynne R. Wilkens
- Marina Kvaskoff
- Mary K Townsend
- Mia M. Gaudet
- Michael E Jones
- N Charlotte Onland-Moret
- Nicolas Wentzensen
- Patricia Hartge
- Piet A van den Brandt
- Pilar Amiano
- Renée Turzanski Fortner
- Roger L. Milne
- Rudolf Kaaks
- Ruth Travis
- Shelley S. Tworoger
- Synnove F. Knutsen
- Thomas E. Rohan
- Ulrike Peters
- Veronica W. Setiawan
- Victoria A. Kirsh
Organizations
- Aarhus University
- Albert Einstein College of Medicine
- American Cancer Society
- Cancer Council Victoria
- Duke University
- Fred Hutchinson Cancer Center
- George Washington University
- German Cancer Research Center
- H. Lee Moffitt Cancer Center & Research Institute
- Harvard Medical School
- Harvard University
- Imperial College London
- Institute of Cancer Research
- Karolinska Institutet
- Maastricht University
- Monash University
- NYU Langone Health
- National Cancer Institute
- National Institute of Environmental Health Sciences
- National Institutes of Health
- Paris-Saclay University
- Umeå University
- United States Department of Defense
- University of Melbourne
- University of Minnesota
- University of Oxford
- University of Toronto
- University of Tromsø – The Arctic University of Norway
- University of Washington
- Uppsala University
- Utrecht University