1. Ovarian Cancer Risk Factors by Histologic Subtype: An Analysis From the Ovarian Cancer Cohort Consortium.
- Author
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Wentzensen N, Poole EM, Trabert B, White E, Arslan AA, Patel AV, Setiawan VW, Visvanathan K, Weiderpass E, Adami HO, 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 WP, Lacey JV Jr, Lee IM, 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, and Tworoger SS
- Subjects
- Adenocarcinoma, Clear Cell epidemiology, Adenocarcinoma, Clear Cell pathology, Adenocarcinoma, Mucinous epidemiology, Adenocarcinoma, Mucinous pathology, Adult, Asia epidemiology, Carcinoma, Endometrioid epidemiology, Carcinoma, Endometrioid pathology, Carcinoma, Ovarian Epithelial, Cystadenocarcinoma, Serous epidemiology, Cystadenocarcinoma, Serous pathology, Europe epidemiology, Female, Humans, Middle Aged, North America epidemiology, Proportional Hazards Models, Risk Factors, Neoplasms, Glandular and Epithelial epidemiology, Neoplasms, Glandular and Epithelial pathology, Ovarian Neoplasms epidemiology, Ovarian Neoplasms pathology
- Abstract
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., Competing Interests: Authors’ disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article., (© 2016 by American Society of Clinical Oncology.)
- Published
- 2016
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