Multiple Miscarriages Are Associated with the Risk of Ovarian Cancer: Results from the European Prospective Investigation into Cancer and Nutrition

Marieke G. M. Braem; N. Charlotte Onland-Moret; Leo J. Schouten; Roy F. P. M. Kruitwagen; Annekatrin Lukanova; Naomi E. Allen; Petra A. Wark; Anne Tjonneland; Louise Hansen; Christina Marie Brauner; Kim Overvad; Francoise Clavel-Chapelon; Nathalie Chabbert-Buffet; Birgit Teucher; Anna Floegel; Heiner Boeing; Antonia Trichopoulou; George Adarakis; Maria Plada; Sabina Rinaldi; Veronika Fedirko; Isabelle Romieu; Valeria Pala; Rocco Galasso; Carlotta Sacerdote; Domenico Palli; Rosario Tumino; H. Bas Bueno-de-Mesquita; Inger Torhild Gram; Oxana Gavrilyuk; Eiliv Lund; Maria-Jose Sanchez; Catalina Bonet; Maria-Dolores Chirlaque; Nerea Larranaga; Aurelio Barricarte Gurrea; Jose R. Quiros; Annika Idahl; Nina Ohlson; Eva Lundin; Karin Jirstrom; Salma Butt; Konstantinos K. Tsilidis; Kay-Tee Khaw; Nick Wareham; Elio Riboli; Rudolf Kaaks; Petra H. M. Peeters

doi:10.1371/journal.pone.0037141

Multiple Miscarriages Are Associated with the Risk of Ovarian Cancer: Results from the European Prospective Investigation into Cancer and Nutrition

Marieke G. M. Braem^*, N. Charlotte Onland-Moret, Leo J. Schouten, Roy F. P. M. Kruitwagen, Annekatrin Lukanova, Naomi E. Allen, Petra A. Wark, Anne Tjonneland, Louise Hansen, Christina Marie Brauner, Kim Overvad, Francoise Clavel-Chapelon, Nathalie Chabbert-Buffet, Birgit Teucher, Anna Floegel, Heiner Boeing, Antonia Trichopoulou, George Adarakis, Maria Plada, Sabina RinaldiVeronika Fedirko, Isabelle Romieu, Valeria Pala, Rocco Galasso, Carlotta Sacerdote, Domenico Palli, Rosario Tumino, H. Bas Bueno-de-Mesquita, Inger Torhild Gram, Oxana Gavrilyuk, Eiliv Lund, Maria-Jose Sanchez, Catalina Bonet, Maria-Dolores Chirlaque, Nerea Larranaga, Aurelio Barricarte Gurrea, Jose R. Quiros, Annika Idahl, Nina Ohlson, Eva Lundin, Karin Jirstrom, Salma Butt, Konstantinos K. Tsilidis, Kay-Tee Khaw, Nick Wareham, Elio Riboli, Rudolf Kaaks, Petra H. M. Peeters

^*Corresponding author for this work

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

Abstract

While the risk of ovarian cancer clearly reduces with each full-term pregnancy, the effect of incomplete pregnancies is unclear. We investigated whether incomplete pregnancies (miscarriages and induced abortions) are associated with risk of epithelial ovarian cancer. This observational study was carried out in female participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). A total of 274,442 women were followed from 1992 until 2010. The baseline questionnaire elicited information on miscarriages and induced abortions, reproductive history, and lifestyle-related factors. During a median follow-up of 11.5 years, 1,035 women were diagnosed with incident epithelial ovarian cancer. Despite the lack of an overall association (ever vs. never), risk of ovarian cancer was higher among women with multiple incomplete pregnancies (HR >= 4vs.0: 1.74, 95% CI: 1.20-2.70; number of cases in this category: n = 23). This association was particularly evident for multiple miscarriages (HR >= 4vs.0: 1.99, 95% CI: 1.06-3.73; number of cases in this category: n = 10), with no significant association for multiple induced abortions (HR >= 4vs.0: 1.46, 95% CI: 0.68-3.14; number of cases in this category: n = 7). Our findings suggest that multiple miscarriages are associated with an increased risk of epithelial ovarian cancer, possibly through a shared cluster of etiological factors or a common underlying pathology. These findings should be interpreted with caution as this is the first study to show this association and given the small number of cases in the highest exposure categories.

Original language	English
Article number	e37141
Journal	PLOS ONE
Volume	7
Issue number	5
DOIs	https://doi.org/10.1371/journal.pone.0037141
Publication status	Published - 18 May 2012

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10.1371/journal.pone.0037141Licence: CC BY

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Braem, M. G. M., Onland-Moret, N. C., Schouten, L. J., Kruitwagen, R. F. P. M., Lukanova, A., Allen, N. E., Wark, P. A., Tjonneland, A., Hansen, L., Brauner, C. M., Overvad, K., Clavel-Chapelon, F., Chabbert-Buffet, N., Teucher, B., Floegel, A., Boeing, H., Trichopoulou, A., Adarakis, G., Plada, M., ... Peeters, P. H. M. (2012). Multiple Miscarriages Are Associated with the Risk of Ovarian Cancer: Results from the European Prospective Investigation into Cancer and Nutrition. PLOS ONE, 7(5), Article e37141. https://doi.org/10.1371/journal.pone.0037141

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title = "Multiple Miscarriages Are Associated with the Risk of Ovarian Cancer: Results from the European Prospective Investigation into Cancer and Nutrition",

abstract = "While the risk of ovarian cancer clearly reduces with each full-term pregnancy, the effect of incomplete pregnancies is unclear. We investigated whether incomplete pregnancies (miscarriages and induced abortions) are associated with risk of epithelial ovarian cancer. This observational study was carried out in female participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). A total of 274,442 women were followed from 1992 until 2010. The baseline questionnaire elicited information on miscarriages and induced abortions, reproductive history, and lifestyle-related factors. During a median follow-up of 11.5 years, 1,035 women were diagnosed with incident epithelial ovarian cancer. Despite the lack of an overall association (ever vs. never), risk of ovarian cancer was higher among women with multiple incomplete pregnancies (HR >= 4vs.0: 1.74, 95% CI: 1.20-2.70; number of cases in this category: n = 23). This association was particularly evident for multiple miscarriages (HR >= 4vs.0: 1.99, 95% CI: 1.06-3.73; number of cases in this category: n = 10), with no significant association for multiple induced abortions (HR >= 4vs.0: 1.46, 95% CI: 0.68-3.14; number of cases in this category: n = 7). Our findings suggest that multiple miscarriages are associated with an increased risk of epithelial ovarian cancer, possibly through a shared cluster of etiological factors or a common underlying pathology. These findings should be interpreted with caution as this is the first study to show this association and given the small number of cases in the highest exposure categories.",

author = "Braem, {Marieke G. M.} and Onland-Moret, {N. Charlotte} and Schouten, {Leo J.} and Kruitwagen, {Roy F. P. M.} and Annekatrin Lukanova and Allen, {Naomi E.} and Wark, {Petra A.} and Anne Tjonneland and Louise Hansen and Brauner, {Christina Marie} and Kim Overvad and Francoise Clavel-Chapelon and Nathalie Chabbert-Buffet and Birgit Teucher and Anna Floegel and Heiner Boeing and Antonia Trichopoulou and George Adarakis and Maria Plada and Sabina Rinaldi and Veronika Fedirko and Isabelle Romieu and Valeria Pala and Rocco Galasso and Carlotta Sacerdote and Domenico Palli and Rosario Tumino and Bueno-de-Mesquita, {H. Bas} and Gram, {Inger Torhild} and Oxana Gavrilyuk and Eiliv Lund and Maria-Jose Sanchez and Catalina Bonet and Maria-Dolores Chirlaque and Nerea Larranaga and {Barricarte Gurrea}, Aurelio and Quiros, {Jose R.} and Annika Idahl and Nina Ohlson and Eva Lundin and Karin Jirstrom and Salma Butt and Tsilidis, {Konstantinos K.} and Kay-Tee Khaw and Nick Wareham and Elio Riboli and Rudolf Kaaks and Peeters, {Petra H. M.}",

year = "2012",

month = may,

day = "18",

doi = "10.1371/journal.pone.0037141",

language = "English",

volume = "7",

journal = "PLOS ONE",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "5",

}

Braem, MGM, Onland-Moret, NC, Schouten, LJ , Kruitwagen, RFPM, Lukanova, A, Allen, NE, Wark, PA, Tjonneland, A, Hansen, L, Brauner, CM, Overvad, K, Clavel-Chapelon, F, Chabbert-Buffet, N, Teucher, B, Floegel, A, Boeing, H, Trichopoulou, A, Adarakis, G, Plada, M, Rinaldi, S, Fedirko, V, Romieu, I, Pala, V, Galasso, R, Sacerdote, C, Palli, D, Tumino, R, Bueno-de-Mesquita, HB, Gram, IT, Gavrilyuk, O, Lund, E, Sanchez, M-J, Bonet, C, Chirlaque, M-D, Larranaga, N, Barricarte Gurrea, A, Quiros, JR, Idahl, A, Ohlson, N, Lundin, E, Jirstrom, K, Butt, S, Tsilidis, KK, Khaw, K-T, Wareham, N, Riboli, E, Kaaks, R & Peeters, PHM 2012, 'Multiple Miscarriages Are Associated with the Risk of Ovarian Cancer: Results from the European Prospective Investigation into Cancer and Nutrition', PLOS ONE, vol. 7, no. 5, e37141. https://doi.org/10.1371/journal.pone.0037141

TY - JOUR

T1 - Multiple Miscarriages Are Associated with the Risk of Ovarian Cancer: Results from the European Prospective Investigation into Cancer and Nutrition

AU - Braem, Marieke G. M.

AU - Onland-Moret, N. Charlotte

AU - Schouten, Leo J.

AU - Kruitwagen, Roy F. P. M.

AU - Lukanova, Annekatrin

AU - Allen, Naomi E.

AU - Wark, Petra A.

AU - Tjonneland, Anne

AU - Hansen, Louise

AU - Brauner, Christina Marie

AU - Overvad, Kim

AU - Clavel-Chapelon, Francoise

AU - Chabbert-Buffet, Nathalie

AU - Teucher, Birgit

AU - Floegel, Anna

AU - Boeing, Heiner

AU - Trichopoulou, Antonia

AU - Adarakis, George

AU - Plada, Maria

AU - Rinaldi, Sabina

AU - Fedirko, Veronika

AU - Romieu, Isabelle

AU - Pala, Valeria

AU - Galasso, Rocco

AU - Sacerdote, Carlotta

AU - Palli, Domenico

AU - Tumino, Rosario

AU - Bueno-de-Mesquita, H. Bas

AU - Gram, Inger Torhild

AU - Gavrilyuk, Oxana

AU - Lund, Eiliv

AU - Sanchez, Maria-Jose

AU - Bonet, Catalina

AU - Chirlaque, Maria-Dolores

AU - Larranaga, Nerea

AU - Barricarte Gurrea, Aurelio

AU - Quiros, Jose R.

AU - Idahl, Annika

AU - Ohlson, Nina

AU - Lundin, Eva

AU - Jirstrom, Karin

AU - Butt, Salma

AU - Tsilidis, Konstantinos K.

AU - Khaw, Kay-Tee

AU - Wareham, Nick

AU - Riboli, Elio

AU - Kaaks, Rudolf

AU - Peeters, Petra H. M.

PY - 2012/5/18

Y1 - 2012/5/18

N2 - While the risk of ovarian cancer clearly reduces with each full-term pregnancy, the effect of incomplete pregnancies is unclear. We investigated whether incomplete pregnancies (miscarriages and induced abortions) are associated with risk of epithelial ovarian cancer. This observational study was carried out in female participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). A total of 274,442 women were followed from 1992 until 2010. The baseline questionnaire elicited information on miscarriages and induced abortions, reproductive history, and lifestyle-related factors. During a median follow-up of 11.5 years, 1,035 women were diagnosed with incident epithelial ovarian cancer. Despite the lack of an overall association (ever vs. never), risk of ovarian cancer was higher among women with multiple incomplete pregnancies (HR >= 4vs.0: 1.74, 95% CI: 1.20-2.70; number of cases in this category: n = 23). This association was particularly evident for multiple miscarriages (HR >= 4vs.0: 1.99, 95% CI: 1.06-3.73; number of cases in this category: n = 10), with no significant association for multiple induced abortions (HR >= 4vs.0: 1.46, 95% CI: 0.68-3.14; number of cases in this category: n = 7). Our findings suggest that multiple miscarriages are associated with an increased risk of epithelial ovarian cancer, possibly through a shared cluster of etiological factors or a common underlying pathology. These findings should be interpreted with caution as this is the first study to show this association and given the small number of cases in the highest exposure categories.

AB - While the risk of ovarian cancer clearly reduces with each full-term pregnancy, the effect of incomplete pregnancies is unclear. We investigated whether incomplete pregnancies (miscarriages and induced abortions) are associated with risk of epithelial ovarian cancer. This observational study was carried out in female participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). A total of 274,442 women were followed from 1992 until 2010. The baseline questionnaire elicited information on miscarriages and induced abortions, reproductive history, and lifestyle-related factors. During a median follow-up of 11.5 years, 1,035 women were diagnosed with incident epithelial ovarian cancer. Despite the lack of an overall association (ever vs. never), risk of ovarian cancer was higher among women with multiple incomplete pregnancies (HR >= 4vs.0: 1.74, 95% CI: 1.20-2.70; number of cases in this category: n = 23). This association was particularly evident for multiple miscarriages (HR >= 4vs.0: 1.99, 95% CI: 1.06-3.73; number of cases in this category: n = 10), with no significant association for multiple induced abortions (HR >= 4vs.0: 1.46, 95% CI: 0.68-3.14; number of cases in this category: n = 7). Our findings suggest that multiple miscarriages are associated with an increased risk of epithelial ovarian cancer, possibly through a shared cluster of etiological factors or a common underlying pathology. These findings should be interpreted with caution as this is the first study to show this association and given the small number of cases in the highest exposure categories.

U2 - 10.1371/journal.pone.0037141

DO - 10.1371/journal.pone.0037141

M3 - Article

C2 - 22623987

SN - 1932-6203

VL - 7

JO - PLOS ONE

JF - PLOS ONE

IS - 5

M1 - e37141

ER -