Ovarian Cancer Risk Factors by Histologic Subtype: An Analysis From the Ovarian Cancer Cohort Consortium.
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Date
2016-08-20Author
Wentzensen, N
Poole, EM
Trabert, B
White, E
Arslan, AA
Patel, AV
Setiawan, VW
Visvanathan, K
Weiderpass, E
Adami, H-O
Black, A
Bernstein, L
Brinton, LA
Buring, J
Butler, LM
Chamosa, S
Clendenen, TV
Dossus, L
Fortner, R
Gapstur, SM
Gaudet, MM
Gram, IT
Hartge, P
Hoffman-Bolton, J
Idahl, A
Jones, M
Kaaks, R
Kirsh, V
Koh, W-P
Lacey, JV
Lee, I-M
Lundin, E
Merritt, MA
Onland-Moret, NC
Peters, U
Poynter, JN
Rinaldi, S
Robien, K
Rohan, T
Sandler, DP
Schairer, C
Schouten, LJ
Sjöholm, LK
Sieri, S
Swerdlow, A
Tjonneland, A
Travis, R
Trichopoulou, A
van den Brandt, PA
Wilkens, L
Wolk, A
Yang, HP
Zeleniuch-Jacquotte, A
Tworoger, SS
Type
Journal Article
Metadata
Show full item recordAbstract
PURPOSE: An understanding of the etiologic heterogeneity of ovarian cancer is important for improving prevention, early detection, and therapeutic approaches. We evaluated 14 hormonal, reproductive, and lifestyle factors by histologic subtype in the Ovarian Cancer Cohort Consortium (OC3). PATIENTS AND METHODS: Among 1.3 million women from 21 studies, 5,584 invasive epithelial ovarian cancers were identified (3,378 serous, 606 endometrioid, 331 mucinous, 269 clear cell, 1,000 other). By using competing-risks Cox proportional hazards regression stratified by study and birth year and adjusted for age, parity, and oral contraceptive use, we assessed associations for all invasive cancers by histology. Heterogeneity was evaluated by likelihood ratio test. RESULTS: Most risk factors exhibited significant heterogeneity by histology. Higher parity was most strongly associated with endometrioid (relative risk [RR] per birth, 0.78; 95% CI, 0.74 to 0.83) and clear cell (RR, 0.68; 95% CI, 0.61 to 0.76) carcinomas (P value for heterogeneity [P-het] < .001). Similarly, age at menopause, endometriosis, and tubal ligation were only associated with endometrioid and clear cell tumors (P-het ≤ .01). Family history of breast cancer (P-het = .008) had modest heterogeneity. Smoking was associated with an increased risk of mucinous (RR per 20 pack-years, 1.26; 95% CI, 1.08 to 1.46) but a decreased risk of clear cell (RR, 0.72; 95% CI, 0.55 to 0.94) tumors (P-het = .004). Unsupervised clustering by risk factors separated endometrioid, clear cell, and low-grade serous carcinomas from high-grade serous and mucinous carcinomas. CONCLUSION: The heterogeneous associations of risk factors with ovarian cancer subtypes emphasize the importance of conducting etiologic studies by ovarian cancer subtypes. Most established risk factors were more strongly associated with nonserous carcinomas, which demonstrate challenges for risk prediction of serous cancers, the most fatal subtype.
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Subject
Humans
Neoplasms, Glandular and Epithelial
Adenocarcinoma, Clear Cell
Adenocarcinoma, Mucinous
Carcinoma, Endometrioid
Cystadenocarcinoma, Serous
Ovarian Neoplasms
Proportional Hazards Models
Risk Factors
Adult
Middle Aged
North America
Asia
Europe
Female
Carcinoma, Ovarian Epithelial
Research team
Aetiological Epidemiology
Language
eng
License start date
2016-08
Citation
Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2016, 34 (24), pp. 2888 - 2898
Publisher
LIPPINCOTT WILLIAMS & WILKINS