TY - JOUR
T1 - Ovarian cancer risk factors by histologic subtype
T2 - An analysis from the Ovarian Cancer Cohort Consortium
AU - Wentzensen, Nicolas
AU - Poole, Elizabeth M.
AU - Trabert, Britton
AU - White, Emily
AU - Arslan, Alan A.
AU - Patel, Alpa V.
AU - Setiawan, V. Wendy
AU - Visvanathan, Kala
AU - Weiderpass, Elisabete
AU - Adami, Hans Olov
AU - Black, Amanda
AU - Bernstein, Leslie
AU - Brinton, Louise A.
AU - Buring, Julie
AU - Butler, Lesley M.
AU - Chamosa, Saioa
AU - Clendenen, Tess V.
AU - Dossus, Laure
AU - Fortner, Renee
AU - Gapstur, Susan M.
AU - Gaudet, Mia M.
AU - Gram, Inger T.
AU - Hartge, Patricia
AU - Hoffman-Bolton, Judith
AU - Idahl, Annika
AU - Jones, Michael
AU - Kaaks, Rudolf
AU - Kirsh, Victoria
AU - Koh, Woon Puay
AU - Lacey, James V.
AU - Lee, I. Min
AU - Lundin, Eva
AU - Merritt, Melissa A.
AU - Onland-Moret, N. Charlotte
AU - Peters, Ulrike
AU - Poynter, Jenny N.
AU - Rinaldi, Sabina
AU - Robien, Kim
AU - Rohan, Thomas
AU - Sandler, Dale P.
AU - Schairer, Catherine
AU - Schouten, Leo J.
AU - Sjöholm, Louise K.
AU - Sieri, Sabina
AU - Swerdlow, Anthony
AU - Tjonneland, Anna
AU - Travis, Ruth
AU - Trichopoulou, Antonia
AU - Van Den Brandt, Piet A.
AU - Wilkens, Lynne
AU - Wolk, Alicja
AU - Yang, Hannah P.
AU - Zeleniuch-Jacquotte, Anne
AU - Tworoger, Shelley S.
N1 - Publisher Copyright:
© 2016 by American Society of Clinical Oncology.
PY - 2016/8/20
Y1 - 2016/8/20
N2 - 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.
AB - 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.
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U2 - 10.1200/JCO.2016.66.8178
DO - 10.1200/JCO.2016.66.8178
M3 - Article
C2 - 27325851
AN - SCOPUS:84980507559
SN - 0732-183X
VL - 34
SP - 2888
EP - 2898
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 24
ER -