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Int J Cancer. 2019 Jul 1;145(1):58-69. doi: 10.1002/ijc.32075. Epub 2019 Jan 14.

Ovarian cancer risk factors by tumor aggressiveness: An analysis from the Ovarian Cancer Cohort Consortium.

Author information

1
Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
2
Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
3
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Washington, D.C.
4
Fred Hutchinson Cancer Research Center, Seattle, WA.
5
New York University School of Medicine, New York, NY.
6
Epidemiology Research Program, American Cancer Society, Atlanta, GA.
7
University of Southern California, Los Angeles, CA.
8
Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
9
Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway.
10
Department of Research, Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway.
11
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
12
Genetic Epidemiology Group, Folkhälsan Research Center, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
13
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.
14
City of Hope, Duarte, CA.
15
Division of Preventive Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
16
CESP "Health across Generations," INSERM, Univ Paris-Sud, UVSQ, Univ Paris-Saclay, Villejuif, France.
17
Gustave Roussy, Villejuif, France.
18
Loma Linda University, Loma Linda, CA.
19
Cancer Epidemiology & Intelligence Division, Cancer Council Victoria, Melbourne, Australia.
20
Centre for Epidemiology and Biostatistics, School of Population and Global Health, The University of Melbourne, Melbourne, Australia.
21
Department of Clinical Sciences, Obstetrics and Gynecology, Umeå University, Umeå, Sweden.
22
Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.
23
Health Services and Systems Research, Duke-NUS Medical School Singapore, Singapore.
24
Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
25
Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI.
26
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place, London, W2 1PG, United Kingdom.
27
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
28
Department of Pediatrics, University of Minnesota, Minneapolis, MN.
29
International Agency for Research on Cancer, Lyon, France.
30
Department of Exercise and Nutrition Sciences, Milken Institute School of Public Health, George Washington University, Washington, D.C.
31
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY.
32
Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria ibs.GRANADA. Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain.
33
CIBER de Epidemiología y Salud Pública (CIBERESP), Spain.
34
GROW-School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands.
35
Danish Cancer Society Research Center, Copenhagen, Denmark.
36
Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL.
37
Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
38
Hellenic Health Foundation, Athens, Greece.
39
WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Dept. of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Greece.
40
HuGeF Foundation, Torino, Italy.
41
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

Abstract

Ovarian cancer risk factors differ by histotype; however, within subtype, there is substantial variability in outcomes. We hypothesized that risk factor profiles may influence tumor aggressiveness, defined by time between diagnosis and death, independent of histology. Among 1.3 million women from 21 prospective cohorts, 4,584 invasive epithelial ovarian cancers were identified and classified as highly aggressive (death in <1 year, n = 864), very aggressive (death in 1 to < 3 years, n = 1,390), moderately aggressive (death in 3 to < 5 years, n = 639), and less aggressive (lived 5+ years, n = 1,691). Using competing risks Cox proportional hazards regression, we assessed heterogeneity of associations by tumor aggressiveness for all cases and among serous and endometrioid/clear cell tumors. Associations between parity (phet = 0.01), family history of ovarian cancer (phet = 0.02), body mass index (BMI; phet ≤ 0.04) and smoking (phet < 0.01) and ovarian cancer risk differed by aggressiveness. A first/single pregnancy, relative to nulliparity, was inversely associated with highly aggressive disease (HR: 0.72; 95% CI [0.58-0.88]), no association was observed for subsequent pregnancies (per pregnancy, 0.97 [0.92-1.02]). In contrast, first and subsequent pregnancies were similarly associated with less aggressive disease (0.87 for both). Family history of ovarian cancer was only associated with risk of less aggressive disease (1.94 [1.47-2.55]). High BMI (≥35 vs. 20 to < 25 kg/m2 , 1.93 [1.46-2.56] and current smoking (vs. never, 1.30 [1.07-1.57]) were associated with increased risk of highly aggressive disease. Results were similar within histotypes. Ovarian cancer risk factors may be directly associated with subtypes defined by tumor aggressiveness, rather than through differential effects on histology. Studies to assess biological pathways are warranted.

KEYWORDS:

aggressiveness; ovarian cancer; prospective cohort; risk factors; subtypes

PMID:
30561796
PMCID:
PMC6488363
[Available on 2020-07-01]
DOI:
10.1002/ijc.32075

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