Expanding Our Understanding of Ovarian Cancer Risk: The Role of Incomplete Pregnancies

Alice W. Lee; Stacey Rosenzweig; Ashley Wiensch; Susan J. Ramus; Usha Menon; Aleksandra Gentry-Maharaj; Argyrios Ziogas; Hoda Anton-Culver; Alice S. Whittemore; Weiva Sieh; Joseph H. Rothstein; Valerie Mcguire; Nicolas Wentzensen; Elisa V. Bandera; Bo Qin; Kathryn L. Terry; Daniel W. Cramer; Linda Titus; Joellen M. Schildkraut; Andrew Berchuck; Ellen L. Goode; Susanne K. Kjaer; Allan Jensen; Susan J. Jordan; Roberta B. Ness; Francesmary Modugno; Kirsten Moysich; Pamela J. Thompson; Marc T. Goodman; Michael E. Carney; Jenny Chang-Claude; Mary Anne Rossing; Holly R. Harris; Jennifer Anne Doherty; Harvey A. Risch; Lilah Khoja; Aliya Alimujiang; Minh Tung Phung; Katharine Brieger; Bhramar Mukherjee; Paul D.P. Pharoah; Anna H. Wu; Malcolm C. Pike; Penelope M. Webb; Celeste Leigh Pearce

doi:10.1093/jnci/djaa099

Expanding Our Understanding of Ovarian Cancer Risk: The Role of Incomplete Pregnancies

Alice W. Lee, Stacey Rosenzweig, Ashley Wiensch, Susan J. Ramus, Usha Menon, Aleksandra Gentry-Maharaj, Argyrios Ziogas, Hoda Anton-Culver, Alice S. Whittemore, Weiva Sieh, Joseph H. Rothstein, Valerie Mcguire, Nicolas Wentzensen, Elisa V. Bandera, Bo Qin, Kathryn L. Terry, Daniel W. Cramer, Linda Titus, Joellen M. Schildkraut, Andrew BerchuckEllen L. Goode, Susanne K. Kjaer, Allan Jensen, Susan J. Jordan, Roberta B. Ness, Francesmary Modugno, Kirsten Moysich, Pamela J. Thompson, Marc T. Goodman, Michael E. Carney, Jenny Chang-Claude, Mary Anne Rossing, Holly R. Harris, Jennifer Anne Doherty, Harvey A. Risch, Lilah Khoja, Aliya Alimujiang, Minh Tung Phung, Katharine Brieger, Bhramar Mukherjee, Paul D.P. Pharoah, Anna H. Wu, Malcolm C. Pike, Penelope M. Webb, Celeste Leigh Pearce

Research output: Contribution to journal › Article › peer-review

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Abstract

Background: Parity is associated with decreased risk of invasive ovarian cancer; however, the relationship between incomplete pregnancies and invasive ovarian cancer risk is unclear. This relationship was examined using 15 case-control studies from the Ovarian Cancer Association Consortium (OCAC). Histotype-specific associations, which have not been examined previously with large sample sizes, were also evaluated. Methods: A pooled analysis of 10 470 invasive epithelial ovarian cancer cases and 16 942 controls was conducted. Odds ratios (ORs) and 95% confidence intervals (CIs) for the association between incomplete pregnancies and invasive epithelial ovarian cancer were estimated using logistic regression. All models were conditioned on OCAC study, race and ethnicity, age, and education level and adjusted for number of complete pregnancies, oral contraceptive use, and history of breastfeeding. The same approach was used for histotype-specific analyses. Results: Ever having an incomplete pregnancy was associated with a 16% reduction in ovarian cancer risk (OR = 0.84, 95% CI = 0.79 to 0.89). There was a trend of decreasing risk with increasing number of incomplete pregnancies (2-sided Ptrend <. 001). An inverse association was observed for all major histotypes; it was strongest for clear cell ovarian cancer. Conclusions: Incomplete pregnancies are associated with a reduced risk of invasive epithelial ovarian cancer. Pregnancy, including incomplete pregnancy, was associated with a greater reduction in risk of clear cell ovarian cancer, but the result was broadly consistent across histotypes. Future work should focus on understanding the mechanisms underlying this reduced risk.

Original language	English
Pages (from-to)	301-308
Number of pages	8
Journal	Journal of the National Cancer Institute
Volume	113
Issue number	3
DOIs	https://doi.org/10.1093/jnci/djaa099
State	Published - 1 Mar 2021

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Lee, A. W., Rosenzweig, S., Wiensch, A., Ramus, S. J., Menon, U., Gentry-Maharaj, A., Ziogas, A., Anton-Culver, H., Whittemore, A. S., Sieh, W., Rothstein, J. H., Mcguire, V., Wentzensen, N., Bandera, E. V., Qin, B., Terry, K. L., Cramer, D. W., Titus, L., Schildkraut, J. M., ... Pearce, C. L. (2021). Expanding Our Understanding of Ovarian Cancer Risk: The Role of Incomplete Pregnancies. Journal of the National Cancer Institute, 113(3), 301-308. https://doi.org/10.1093/jnci/djaa099

@article{5f54f6048f634c0397aa295a53492ed4,

title = "Expanding Our Understanding of Ovarian Cancer Risk: The Role of Incomplete Pregnancies",

abstract = "Background: Parity is associated with decreased risk of invasive ovarian cancer; however, the relationship between incomplete pregnancies and invasive ovarian cancer risk is unclear. This relationship was examined using 15 case-control studies from the Ovarian Cancer Association Consortium (OCAC). Histotype-specific associations, which have not been examined previously with large sample sizes, were also evaluated. Methods: A pooled analysis of 10 470 invasive epithelial ovarian cancer cases and 16 942 controls was conducted. Odds ratios (ORs) and 95% confidence intervals (CIs) for the association between incomplete pregnancies and invasive epithelial ovarian cancer were estimated using logistic regression. All models were conditioned on OCAC study, race and ethnicity, age, and education level and adjusted for number of complete pregnancies, oral contraceptive use, and history of breastfeeding. The same approach was used for histotype-specific analyses. Results: Ever having an incomplete pregnancy was associated with a 16% reduction in ovarian cancer risk (OR = 0.84, 95% CI = 0.79 to 0.89). There was a trend of decreasing risk with increasing number of incomplete pregnancies (2-sided Ptrend <. 001). An inverse association was observed for all major histotypes; it was strongest for clear cell ovarian cancer. Conclusions: Incomplete pregnancies are associated with a reduced risk of invasive epithelial ovarian cancer. Pregnancy, including incomplete pregnancy, was associated with a greater reduction in risk of clear cell ovarian cancer, but the result was broadly consistent across histotypes. Future work should focus on understanding the mechanisms underlying this reduced risk.",

author = "Lee, {Alice W.} and Stacey Rosenzweig and Ashley Wiensch and Ramus, {Susan J.} and Usha Menon and Aleksandra Gentry-Maharaj and Argyrios Ziogas and Hoda Anton-Culver and Whittemore, {Alice S.} and Weiva Sieh and Rothstein, {Joseph H.} and Valerie Mcguire and Nicolas Wentzensen and Bandera, {Elisa V.} and Bo Qin and Terry, {Kathryn L.} and Cramer, {Daniel W.} and Linda Titus and Schildkraut, {Joellen M.} and Andrew Berchuck and Goode, {Ellen L.} and Kjaer, {Susanne K.} and Allan Jensen and Jordan, {Susan J.} and Ness, {Roberta B.} and Francesmary Modugno and Kirsten Moysich and Thompson, {Pamela J.} and Goodman, {Marc T.} and Carney, {Michael E.} and Jenny Chang-Claude and Rossing, {Mary Anne} and Harris, {Holly R.} and Doherty, {Jennifer Anne} and Risch, {Harvey A.} and Lilah Khoja and Aliya Alimujiang and Phung, {Minh Tung} and Katharine Brieger and Bhramar Mukherjee and Pharoah, {Paul D.P.} and Wu, {Anna H.} and Pike, {Malcolm C.} and Webb, {Penelope M.} and Pearce, {Celeste Leigh}",

note = "Funding Information: OCAC funding: This work was supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07). The scientific development and funding for this project were in part supported by the US National Cancer Institute at the National Institutes of Health GAME-ON Post-GWAS Initiative (grant number U19-CA148112). AUS: This work was supported by the US Army Medical Research and Materiel Command (grant number DAMD17-01-1-0729), The Cancer Council Tasmania and The Cancer Foundation of Western Australia, and the National Health and Medical Research Council of Australia (grant numbers ID199600, ID400413, ID400281). CON: This work was supported by the National Institutes of Health (grant numbers R01-CA063678, R01-CA074850; R01-CA080742). DOV: This work was supported by National Institutes of Health (grant numbers R01- CA112523 and R01-CA87538). HRH is supported by the National Institutes of Health (grant number K22 CA193860). GER: This work was supported by the German Federal Ministry of Education and Research, Programme of Clinical Biomedical Research (grant number 01 GB 9401) and the German Cancer Research Center (DKFZ). HAW: This work was supported by the US National Institutes of Health (grant numbers R01-CA58598, N01-CN-55424, N01-PC-67001). HOP: This work was supported by the Department of Defense (grant number DAMD17-02-1-0669) and the National Cancer Institute at the National Institutes of Health (grant numbers K07-CA080668, R01-CA95023, P50-CA159981MAL). MAL: This work was supported by the National Cancer Institute at the National Institutes for Health (grant number R01- CA61107), the Danish Cancer Society (grant number 94 222 52), and the Mermaid I project. NCO: This work was supported by the National Institutes of Health (grant number R01-CA76016) and the Department of Defense (grant number DAMD17-02-1-0666). NEC: This work was supported by the National Institutes of Health (grant numbers R01-CA54419, P50- CA105009) and the Department of Defense (grant number W81XWH-10-1-02802). NJO: This work was supported by the National Cancer Institute at the National Institutes for Health (grant number NIH-K07 CA095666, R01-CA83918, NIH-K22-CA138563, P30-CA072720) and the Cancer Institute of New Jersey. POL: This work was supported by the Intramural Research Program of the National Cancer Institute. STA: This work was supported by the National Institutes of Health (grant numbers U01 CA71966, U01 CA69417). UCI: This work was supported by the National Institutes of Health (grant number R01-CA058860) and the Lon V Smith Foundation (grant number LVS-39420). UKO: This work was supported by The Eve Appeal (The Oak Foundation) and the National Institute for Health Research University College London Hospitals Biomedical Research Centre. UM and AGM received support from MRC core funding (MR-UU-12023). USC: This work was supported by the National Institutes of Health (grant numbers P01CA17054, P30CA14089, R01CA61132, N01PC67010, R03CA113148, R03CA115195, N01CN025403) and California Cancer Research Program (grant numbers 00-01389 V-20170, 2II0200). MCP was supported in part through the NIH/NCI Support Grant P30 CA008748 to Memorial Sloan Kettering Cancer Center. AWL was supported in part through a Scientific Scholar Award from the Rivkin Center for Ovarian Cancer. Publisher Copyright: {\textcopyright} 2020 The Author(s).",

year = "2021",

month = mar,

day = "1",

doi = "10.1093/jnci/djaa099",

language = "English",

volume = "113",

pages = "301--308",

journal = "Journal of the National Cancer Institute",

issn = "0027-8874",

publisher = "Oxford University Press",

number = "3",

}

Lee, AW, Rosenzweig, S, Wiensch, A, Ramus, SJ, Menon, U, Gentry-Maharaj, A, Ziogas, A, Anton-Culver, H, Whittemore, AS, Sieh, W , Rothstein, JH, Mcguire, V, Wentzensen, N, Bandera, EV, Qin, B, Terry, KL, Cramer, DW, Titus, L, Schildkraut, JM, Berchuck, A, Goode, EL, Kjaer, SK, Jensen, A, Jordan, SJ, Ness, RB, Modugno, F, Moysich, K, Thompson, PJ, Goodman, MT, Carney, ME, Chang-Claude, J, Rossing, MA, Harris, HR, Doherty, JA, Risch, HA, Khoja, L, Alimujiang, A, Phung, MT, Brieger, K, Mukherjee, B, Pharoah, PDP, Wu, AH, Pike, MC, Webb, PM & Pearce, CL 2021, 'Expanding Our Understanding of Ovarian Cancer Risk: The Role of Incomplete Pregnancies', Journal of the National Cancer Institute, vol. 113, no. 3, pp. 301-308. https://doi.org/10.1093/jnci/djaa099

TY - JOUR

T1 - Expanding Our Understanding of Ovarian Cancer Risk

T2 - The Role of Incomplete Pregnancies

AU - Lee, Alice W.

AU - Rosenzweig, Stacey

AU - Wiensch, Ashley

AU - Ramus, Susan J.

AU - Menon, Usha

AU - Gentry-Maharaj, Aleksandra

AU - Ziogas, Argyrios

AU - Anton-Culver, Hoda

AU - Whittemore, Alice S.

AU - Sieh, Weiva

AU - Rothstein, Joseph H.

AU - Mcguire, Valerie

AU - Wentzensen, Nicolas

AU - Bandera, Elisa V.

AU - Qin, Bo

AU - Terry, Kathryn L.

AU - Cramer, Daniel W.

AU - Titus, Linda

AU - Schildkraut, Joellen M.

AU - Berchuck, Andrew

AU - Goode, Ellen L.

AU - Kjaer, Susanne K.

AU - Jensen, Allan

AU - Jordan, Susan J.

AU - Ness, Roberta B.

AU - Modugno, Francesmary

AU - Moysich, Kirsten

AU - Thompson, Pamela J.

AU - Goodman, Marc T.

AU - Carney, Michael E.

AU - Chang-Claude, Jenny

AU - Rossing, Mary Anne

AU - Harris, Holly R.

AU - Doherty, Jennifer Anne

AU - Risch, Harvey A.

AU - Khoja, Lilah

AU - Alimujiang, Aliya

AU - Phung, Minh Tung

AU - Brieger, Katharine

AU - Mukherjee, Bhramar

AU - Pharoah, Paul D.P.

AU - Wu, Anna H.

AU - Pike, Malcolm C.

AU - Webb, Penelope M.

AU - Pearce, Celeste Leigh

N1 - Funding Information: OCAC funding: This work was supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07). The scientific development and funding for this project were in part supported by the US National Cancer Institute at the National Institutes of Health GAME-ON Post-GWAS Initiative (grant number U19-CA148112). AUS: This work was supported by the US Army Medical Research and Materiel Command (grant number DAMD17-01-1-0729), The Cancer Council Tasmania and The Cancer Foundation of Western Australia, and the National Health and Medical Research Council of Australia (grant numbers ID199600, ID400413, ID400281). CON: This work was supported by the National Institutes of Health (grant numbers R01-CA063678, R01-CA074850; R01-CA080742). DOV: This work was supported by National Institutes of Health (grant numbers R01- CA112523 and R01-CA87538). HRH is supported by the National Institutes of Health (grant number K22 CA193860). GER: This work was supported by the German Federal Ministry of Education and Research, Programme of Clinical Biomedical Research (grant number 01 GB 9401) and the German Cancer Research Center (DKFZ). HAW: This work was supported by the US National Institutes of Health (grant numbers R01-CA58598, N01-CN-55424, N01-PC-67001). HOP: This work was supported by the Department of Defense (grant number DAMD17-02-1-0669) and the National Cancer Institute at the National Institutes of Health (grant numbers K07-CA080668, R01-CA95023, P50-CA159981MAL). MAL: This work was supported by the National Cancer Institute at the National Institutes for Health (grant number R01- CA61107), the Danish Cancer Society (grant number 94 222 52), and the Mermaid I project. NCO: This work was supported by the National Institutes of Health (grant number R01-CA76016) and the Department of Defense (grant number DAMD17-02-1-0666). NEC: This work was supported by the National Institutes of Health (grant numbers R01-CA54419, P50- CA105009) and the Department of Defense (grant number W81XWH-10-1-02802). NJO: This work was supported by the National Cancer Institute at the National Institutes for Health (grant number NIH-K07 CA095666, R01-CA83918, NIH-K22-CA138563, P30-CA072720) and the Cancer Institute of New Jersey. POL: This work was supported by the Intramural Research Program of the National Cancer Institute. STA: This work was supported by the National Institutes of Health (grant numbers U01 CA71966, U01 CA69417). UCI: This work was supported by the National Institutes of Health (grant number R01-CA058860) and the Lon V Smith Foundation (grant number LVS-39420). UKO: This work was supported by The Eve Appeal (The Oak Foundation) and the National Institute for Health Research University College London Hospitals Biomedical Research Centre. UM and AGM received support from MRC core funding (MR-UU-12023). USC: This work was supported by the National Institutes of Health (grant numbers P01CA17054, P30CA14089, R01CA61132, N01PC67010, R03CA113148, R03CA115195, N01CN025403) and California Cancer Research Program (grant numbers 00-01389 V-20170, 2II0200). MCP was supported in part through the NIH/NCI Support Grant P30 CA008748 to Memorial Sloan Kettering Cancer Center. AWL was supported in part through a Scientific Scholar Award from the Rivkin Center for Ovarian Cancer. Publisher Copyright: © 2020 The Author(s).

PY - 2021/3/1

Y1 - 2021/3/1

N2 - Background: Parity is associated with decreased risk of invasive ovarian cancer; however, the relationship between incomplete pregnancies and invasive ovarian cancer risk is unclear. This relationship was examined using 15 case-control studies from the Ovarian Cancer Association Consortium (OCAC). Histotype-specific associations, which have not been examined previously with large sample sizes, were also evaluated. Methods: A pooled analysis of 10 470 invasive epithelial ovarian cancer cases and 16 942 controls was conducted. Odds ratios (ORs) and 95% confidence intervals (CIs) for the association between incomplete pregnancies and invasive epithelial ovarian cancer were estimated using logistic regression. All models were conditioned on OCAC study, race and ethnicity, age, and education level and adjusted for number of complete pregnancies, oral contraceptive use, and history of breastfeeding. The same approach was used for histotype-specific analyses. Results: Ever having an incomplete pregnancy was associated with a 16% reduction in ovarian cancer risk (OR = 0.84, 95% CI = 0.79 to 0.89). There was a trend of decreasing risk with increasing number of incomplete pregnancies (2-sided Ptrend <. 001). An inverse association was observed for all major histotypes; it was strongest for clear cell ovarian cancer. Conclusions: Incomplete pregnancies are associated with a reduced risk of invasive epithelial ovarian cancer. Pregnancy, including incomplete pregnancy, was associated with a greater reduction in risk of clear cell ovarian cancer, but the result was broadly consistent across histotypes. Future work should focus on understanding the mechanisms underlying this reduced risk.

AB - Background: Parity is associated with decreased risk of invasive ovarian cancer; however, the relationship between incomplete pregnancies and invasive ovarian cancer risk is unclear. This relationship was examined using 15 case-control studies from the Ovarian Cancer Association Consortium (OCAC). Histotype-specific associations, which have not been examined previously with large sample sizes, were also evaluated. Methods: A pooled analysis of 10 470 invasive epithelial ovarian cancer cases and 16 942 controls was conducted. Odds ratios (ORs) and 95% confidence intervals (CIs) for the association between incomplete pregnancies and invasive epithelial ovarian cancer were estimated using logistic regression. All models were conditioned on OCAC study, race and ethnicity, age, and education level and adjusted for number of complete pregnancies, oral contraceptive use, and history of breastfeeding. The same approach was used for histotype-specific analyses. Results: Ever having an incomplete pregnancy was associated with a 16% reduction in ovarian cancer risk (OR = 0.84, 95% CI = 0.79 to 0.89). There was a trend of decreasing risk with increasing number of incomplete pregnancies (2-sided Ptrend <. 001). An inverse association was observed for all major histotypes; it was strongest for clear cell ovarian cancer. Conclusions: Incomplete pregnancies are associated with a reduced risk of invasive epithelial ovarian cancer. Pregnancy, including incomplete pregnancy, was associated with a greater reduction in risk of clear cell ovarian cancer, but the result was broadly consistent across histotypes. Future work should focus on understanding the mechanisms underlying this reduced risk.

UR - http://www.scopus.com/inward/record.url?scp=85102658101&partnerID=8YFLogxK

U2 - 10.1093/jnci/djaa099

DO - 10.1093/jnci/djaa099

M3 - Article

C2 - 32766851

AN - SCOPUS:85102658101

SN - 0027-8874

VL - 113

SP - 301

EP - 308

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

IS - 3

ER -

Expanding Our Understanding of Ovarian Cancer Risk: The Role of Incomplete Pregnancies

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