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)

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  • Britton Trabert, Division of Cancer Epidemiology and Genetics, National Cancer Institute britton.trabert@nih.gov., USA
  • Shelley S Tworoger, Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida, USA., USA
  • Katie M O'Brien, Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health., USA
  • Mary K Townsend, Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida, USA., USA
  • Renée T Fortner, Division of Cancer Epidemiology, Deutsches Krebsforschungszentrum (DKFZ)., Tyskland
  • Edwin S Iversen, Department of Statistical Science, Duke University., USA
  • Patricia Hartge, Division of Cancer Epidemiology and Genetics, Clinical Genetics Branch, National Cancer Institute, National Institutes of Health., USA
  • Emily White, Cancer Prevention Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA., USA
  • Pilar Amiano, Public Health Division of Gipuzkoa, Basque Government, Spain; Health Research Institute, Biodonostia, San Sebastián, Spain., Spanien
  • Alan A Arslan, Department of Obstetrics and Gynecology, New York University School of Medicine., USA
  • Leslie Bernstein, POPULATION SCIENCE, Beckman Research Institute, City of Hope., USA
  • Louise A Brinton, Division of Cancer Epidemiology and Genetics, Clinical Genetics Branch, National Cancer Institute, National Institutes of Health., USA
  • Julie E Buring, Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America; Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, United States of America., USA
  • Laure Dossus, International Agency for Research on Cancer, Frankrig
  • Gary E Fraser, Center for Nutrition, Healthy Lifestyle and Disease Prevention, School of Public Health, Loma Linda University, Loma Linda, USA., USA
  • Mia M Gaudet, Behavioral and Epidemiology Research Program, American Cancer Society., USA
  • Graham G Giles, Cancer Epidemiology & Intelligence Division, Cancer Council of Victoria, 615 St Kilda Road, Melbourne, VIC, 3004, Australia., Australien
  • Inger T Gram, Department of Community Medicine, University of Tromsø, The Arctic University of Norway, Tromsø, Norway., Norge
  • Holly R Harris, Cancer Prevention Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA., USA
  • Judith Hoffman Bolton, Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD; Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD., USA
  • Annika Idahl, Department of Clinical Science, Obstetrics and Gynecology, Umea University., Sverige
  • Michael E Jones, Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Gaithersburg, Maryland 20877, USA., USA
  • Rudolf Kaaks, Division of Cancer Epidemiology, Deutsches Krebsforschungszentrum (DKFZ)., Tyskland
  • Victoria A Kirsh, Dalla Lana School of Public Health, University of Toronto, Canada
  • Synnove F Knutsen, Department of Epidemiology and Biostatistics, Loma Linda University., USA
  • Marina Kvaskoff, Health across Generations Team, Inserm U1018, Gustave Roussy., Frankrig
  • James V Lacey, Department of Computational and Quantitative Medicine, City of Hope., USA
  • I-Min Lee, Divisions of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA, USA
  • Roger L Milne, Cancer Epidemiology & Intelligence Division, Cancer Council of Victoria, 615 St Kilda Road, Melbourne, VIC, 3004, Australia., Australien
  • N Charlotte Onland-Moret, Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht., Holland
  • Kim Overvad
  • Alpa V Patel, Behavioral and Epidemiology Research Group, American Cancer Society., USA
  • Ulrike Peters, Cancer Prevention Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA., USA
  • Jenny N Poynter, Pediatric Epidemiology and Clinical Research and Masonic Cancer Center, University of Minnesota., USA
  • Elio Riboli, School of Public Health, Imperial College London, London, UK., Storbritannien
  • Kim Robien, Department of Exercise and Nutrition Sciences, Department of Epidemiology and Biostatistics, George Washington University, Milken Institute School of Public Health., USA
  • Thomas E Rohan, Department of Epidemiology and Population Health, Albert Einstein College of Medicine, New York, USA., USA
  • Dale P Sandler, Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health., USA
  • Catherine Schairer, Division of Cancer Epidemiology and Genetics, Clinical Genetics Branch, National Cancer Institute, National Institutes of Health., USA
  • Leo J Schouten, School for Oncology and Developmental Biology (GROW), Department of Epidemiology, Maastricht University Medical Centre., Holland
  • Veronica Wendy Setiawan, Department of Preventive Medicine, University of Southern California, Los Angeles, California 90032, USA., USA
  • Anthony J Swerdlow, Cancer Genomics Research Laboratory, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Gaithersburg, Maryland 20877, USA., USA
  • Ruth C Travis, Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK., Storbritannien
  • Antonia Trichopoulou, Hellenic Health Foundation., Grækenland
  • Piet A van den Brandt, Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Center, Maastricht, the Netherlands., Holland
  • Kala Visvanathan, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, USA
  • Lynne R Wilkens, Department of Epidemiology, University of Hawaii Cancer Center., USA
  • Alicja Wolk, Institute of Environmental Medicine, Karolinska Institute, Sverige
  • Anne Zeleniuch-Jacquotte, Department of Population Health and Perlmutter Cancer Center, New York University School of Medicine, New York City, New York., USA
  • Nicolas Wentzensen, Division of Cancer Epidemiology and Genetics, Clinical Genetics Branch, National Cancer Institute, National Institutes of Health., USA
  • Ovarian Cancer Cohort Consortium (OC3)

Repeated exposure to the acute pro-inflammatory 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 (2045 serous, 319 endometrioid, 184 mucinous, 121 clear cell, 577 other/unknown). Cox models were used to estimate multivariable-adjusted hazard ratios (HR) 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 five-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 ~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 which cumulates through life, suggesting this as an important area for identifying intervention strategies.

OriginalsprogEngelsk
TidsskriftCancer Research
Vol/bind80
Nummer5
Sider (fra-til)1210-1218
Antal sider9
ISSN0008-5472
DOI
StatusUdgivet - mar. 2020

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