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. Gapstur & 34 others Mia 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

95 Citations (Scopus)

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

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Ovarian Neoplasms
Parity
Carcinoma
Neoplasms
Histology
Parturition
Tubal Sterilization
Mucinous Adenocarcinoma
Endometriosis
Oral Contraceptives
Menopause
Cluster Analysis
Life Style
Smoking
Breast Neoplasms

Cite this

Wentzensen, N., Poole, E. M., Trabert, B., White, E., Arslan, A. A., Patel, A. V., ... 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

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

In: Journal of Clinical Oncology, Vol. 34, No. 24, 20.08.2016, p. 2888-2898.

Research output: Contribution to journalArticle

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, 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 & Tworoger, SS 2016, 'Ovarian cancer risk factors by histologic subtype: An analysis from the Ovarian Cancer Cohort Consortium', Journal of Clinical Oncology, vol. 34, no. 24, pp. 2888-2898. https://doi.org/10.1200/JCO.2016.66.8178
Wentzensen, Nicolas ; Poole, Elizabeth M. ; Trabert, Britton ; White, Emily ; Arslan, Alan A. ; Patel, Alpa V. ; Setiawan, V. Wendy ; Visvanathan, Kala ; Weiderpass, Elisabete ; Adami, Hans Olov ; Black, Amanda ; Bernstein, Leslie ; Brinton, Louise A. ; Buring, Julie ; Butler, Lesley M. ; Chamosa, Saioa ; Clendenen, Tess V. ; Dossus, Laure ; Fortner, Renee ; Gapstur, Susan M. ; Gaudet, Mia M. ; Gram, Inger T. ; Hartge, Patricia ; Hoffman-Bolton, Judith ; Idahl, Annika ; Jones, Michael ; Kaaks, Rudolf ; Kirsh, Victoria ; Koh, Woon Puay ; Lacey, James V. ; Lee, I. Min ; Lundin, Eva ; Merritt, Melissa A. ; Onland-Moret, N. Charlotte ; Peters, Ulrike ; Poynter, Jenny N. ; Rinaldi, Sabina ; Robien, Kim ; Rohan, Thomas ; Sandler, Dale P. ; Schairer, Catherine ; Schouten, Leo J. ; Sjöholm, Louise K. ; Sieri, Sabina ; Swerdlow, Anthony ; Tjonneland, Anna ; Travis, Ruth ; Trichopoulou, Antonia ; Van Den Brandt, Piet A. ; Wilkens, Lynne ; Wolk, Alicja ; Yang, Hannah P. ; Zeleniuch-Jacquotte, Anne ; Tworoger, Shelley S. / Ovarian cancer risk factors by histologic subtype : An analysis from the Ovarian Cancer Cohort Consortium. In: Journal of Clinical Oncology. 2016 ; Vol. 34, No. 24. pp. 2888-2898.
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title = "Ovarian cancer risk factors by histologic subtype: An analysis from the Ovarian Cancer Cohort Consortium",
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.",
author = "Nicolas Wentzensen and Poole, {Elizabeth M.} and Britton Trabert and Emily White and Arslan, {Alan A.} and Patel, {Alpa V.} and Setiawan, {V. Wendy} and Kala Visvanathan and Elisabete Weiderpass and Adami, {Hans Olov} and Amanda Black and Leslie Bernstein and Brinton, {Louise A.} and Julie Buring and Butler, {Lesley M.} and Saioa Chamosa and Clendenen, {Tess V.} and Laure Dossus and Renee Fortner and Gapstur, {Susan M.} and Gaudet, {Mia M.} and Gram, {Inger T.} and Patricia Hartge and Judith Hoffman-Bolton and Annika Idahl and Michael Jones and Rudolf Kaaks and Victoria Kirsh and Koh, {Woon Puay} and Lacey, {James V.} and Lee, {I. Min} and Eva Lundin and Merritt, {Melissa A.} and Onland-Moret, {N. Charlotte} and Ulrike Peters and Poynter, {Jenny N.} and Sabina Rinaldi and Kim Robien and Thomas Rohan and Sandler, {Dale P.} and Catherine Schairer and Schouten, {Leo J.} and Sj{\"o}holm, {Louise K.} and Sabina Sieri and Anthony Swerdlow and Anna Tjonneland and Ruth Travis and Antonia Trichopoulou and {Van Den Brandt}, {Piet A.} and Lynne Wilkens and Alicja Wolk and Yang, {Hannah P.} and Anne Zeleniuch-Jacquotte and Tworoger, {Shelley S.}",
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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.

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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