Ovarian cancer risk factors by histologic subtype: An analysis from the Ovarian Cancer Cohort Consortium

Nicolas Wentzensen, Elizabeth M. Poole, Britton Trabert, Emily White, Alan A. Arslan, Alpa V. Patel, V. Wendy Setiawan, Kala Visvanathan, Elisabete Weiderpass, Hans Olov Adami, Amanda Black, Leslie Bernstein, Louise A. Brinton, Julie Buring, Lesley M. Butler, Saioa Chamosa, Tess V. Clendenen, Laure Dossus, Renee Fortner, Susan M. GapsturMia M. Gaudet, Inger T. Gram, Patricia Hartge, Judith Hoffman-Bolton, Annika Idahl, Michael Jones, Rudolf Kaaks, Victoria Kirsh, Woon Puay Koh, James V. Lacey, I. Min Lee, Eva Lundin, Melissa A. Merritt, N. Charlotte Onland-Moret, Ulrike Peters, Jenny N. Poynter, Sabina Rinaldi, Kim Robien, Thomas Rohan, Dale P. Sandler, Catherine Schairer, Leo J. Schouten, Louise K. Sjöholm, Sabina Sieri, Anthony Swerdlow, Anna Tjonneland, Ruth Travis, Antonia Trichopoulou, Piet A. Van Den Brandt, Lynne Wilkens, Alicja Wolk, Hannah P. Yang, Anne Zeleniuch-Jacquotte, Shelley S. Tworoger

Research output: Contribution to journalArticle

145 Scopus citations

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 competingrisks 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.

Original languageEnglish (US)
Pages (from-to)2888-2898
Number of pages11
JournalJournal of Clinical Oncology
Volume34
Issue number24
DOIs
StatePublished - Aug 20 2016

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Wentzensen, N., Poole, E. M., Trabert, B., White, E., Arslan, A. A., Patel, A. V., Setiawan, V. W., Visvanathan, K., Weiderpass, E., Adami, H. O., Black, A., Bernstein, L., Brinton, L. A., Buring, J., Butler, L. M., Chamosa, S., Clendenen, T. V., Dossus, L., Fortner, R., ... Tworoger, S. S. (2016). Ovarian cancer risk factors by histologic subtype: An analysis from the Ovarian Cancer Cohort Consortium. Journal of Clinical Oncology, 34(24), 2888-2898. https://doi.org/10.1200/JCO.2016.66.8178