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, Veronica Wendy Setiawan, Kala Visvanathan, Elisabete Weiderpass, Hans-Olov Adami, Hans‐Olov Adami, Amanda Black, Leslie Bernstein, Louise A Brinton, Julie Buring, Julie E. Buring, Lesley M Butler, Saioa Chamosa, Tess V Clendenen, Laure Dossus, Renée T. Fortner, Renee Fortner, Susan M Gapstur, Mia M Gaudet, Inger T Gram, Inger Torhild Gram, Patricia Hartge, Judith Hoffman–Bolton, Judith Hoffman-Bolton, Annika Idahl, Michael E. Jones, Michael Jones, Rudolf Kaaks, Victoria Kirsh, Victoria A. Kirsh, Woon-Puay Koh, Woon‐Puay Koh, James V Lacey, I-Min Lee, I‐Min Lee, Eva Lundin, Melissa A Merritt, N. Charlotte Onland‐Moret, N Charlotte Onland-Moret, Ulrike Peters, Jenny N Poynter, Sabina Rinaldi, Kim Robien, Thomas E. Rohan, Thomas Rohan, Dale P Sandler, Catherine Schairer, Leo J Schouten, Louise K Sjöholm, Sabina Sieri, Anthony J. Swerdlow, Anthony Swerdlow, Anna Tjonneland, Anne Tjønneland, Ruth C. Travis, Ruth Travis, Antonia Trichopoulou, Piet A van den Brandt, Lynne Wilkens, Lynne R. Wilkens, Alicja Wolk, Hannah Yang, Hannah P Yang, Anne Zeleniuch‐Jacquotte, Anne Zeleniuch-Jacquotte, Shelley S Tworoger
Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2016 · vol. 34(24) , pp. 2888–2898 · doi:10.1200/jco.2016.66.8178 · PMID:27325851 · PMC5012665 · W2462819743
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Risk factors for ovarian cancer exhibit significant heterogeneity by histologic subtype, with most established factors more strongly associated with nonserous carcinomas.

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This study analyzed etiologic heterogeneity of epithelial ovarian cancer by histologic subtype using data from 21 cohort studies within the Ovarian Cancer Cohort Consortium, including 1.3 million women and 5,584 invasive epithelial ovarian cancers. Fourteen hormonal, reproductive, and lifestyle factors were assessed with competing risks Cox models stratified by study and birth year, adjusting for age, parity, and oral contraceptive use, and heterogeneity by histology was tested with likelihood ratio methods. Higher parity was most strongly associated with lower risk of endometrioid (RR per birth 0.78) and clear cell (RR 0.68), and variables including age at menopause, endometriosis, and tubal ligation showed associations limited to endometrioid and clear cell tumors with significant heterogeneity. The paper’s limitation is its observational design, with results restricted to invasive epithelial ovarian cancers and particular histologic categories within the available cohorts. Relevance to endometriosis: endometriosis is explicitly analyzed as a risk factor that is only associated with endometrioid and clear cell ovarian tumors, though the paper’s main focus is subtype-specific ovarian cancer risk factor heterogeneity.

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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.
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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 | Original language | English | |---|---| | Pages (from-to) | 2888-2898 | | Number of pages | 11 | | Journal | Journal of Clinical Oncology | | Volume | 34 | | Issue number | 24 | | DOIs | | | Publication status | Published - 20 Aug 2016 | Fingerprint Dive into the research topics of 'Ovarian Cancer Risk Factors by Histologic Subtype: An Analysis From the Ovarian Cancer Cohort Consortium'. Together they form a unique fingerprint.Cite this - APA - Author - BIBTEX - Harvard - Standard - RIS - Vancouver

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Condition tags

endometriosis

MeSH descriptors

Neoplasms, Glandular and Epithelial Neoplasms, Glandular and Epithelial Ovarian Neoplasms Ovarian Neoplasms Adenocarcinoma, Clear Cell Adenocarcinoma, Clear Cell Adenocarcinoma, Clear Cell Adenocarcinoma, Mucinous Adenocarcinoma, Mucinous Adenocarcinoma, Mucinous Adult Asia Asia Carcinoma, Endometrioid Carcinoma, Endometrioid Carcinoma, Endometrioid Carcinoma, Ovarian Epithelial Cystadenocarcinoma, Serous Cystadenocarcinoma, Serous Cystadenocarcinoma, Serous

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