Factors influencing ovulation and the risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers.

Joanne Kotsopoulos; Jan Lubinski; Jacek Gronwald; Cezary Cybulski; Rochelle Demsky; Susan L Neuhausen; Charmaine Kim-Sing; Nadine Tung; Susan Friedman; Leigha Senter; Jeffrey Weitzel; Beth Karlan; Pal Moller; Ping Sun; Steven A Narod; Henry T Lynch; Christian Singer; Charis Eng; Gillian Mitchell; Tomasz Huzarski; Jeanna McCuaig; Kevin Hughes; Gordon Mills; Parviz Ghadirian; Andrea Eisen; Dawna Gilchrist; Joanne L Blum; Dana Zakalik; Tuya Pal; Mary Daly; Barbara Weber; Carrie Snyder; Taya Fallen; Albert Chudley; John Lunn; Talia Donenberg; Raluca N Kurz; Howard Saal; Judy Garber; Gad Rennert; Kevin Sweet; Ruth Gershoni-Baruch; Christine Rappaport; Edmond Lemire; Dominique Stoppa-Lyonnet; Olufunmilayo I Olopade; Sofia Merajver; Louise Bordeleau; Carey A Cullinane; Eitan Friedman; Wendy McKinnon; Marie Wood; Daniel Rayson; Wendy Meschino; Jane McLennan; Josephine Wagner Costalas; Robert E Reilly; Susan Vadaparampil; Kenneth Offit; Noah Kauff; Jan Klijn; David Euhus; Ava Kwong; Claudine Isaacs; Fergus Couch; Siranoush Manoukian; Tomasz Byrski; Christine Elser; Seema Panchal; Susan Armel; Sonia Nanda; Kelly Metcalfe; Aletta Poll; Barry Rosen; William D Foulkes; Timothy Rebbeck; Peter Ainsworth; Andre Robidoux; Ellen Warner; Lovise Maehle; Michael Osborne; Gareth Evans; Barbara Pasini; Ophira Ginsburg; Stephanie Cohen; Gorski Bohdan; Anna Jakubowska; Janice Little

doi:10.1002/ijc.29386

Factors influencing ovulation and the risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers.

Joanne Kotsopoulos, Jan Lubinski, Jacek Gronwald, Cezary Cybulski, Rochelle Demsky, Susan L Neuhausen, Charmaine Kim-Sing, Nadine Tung, Susan Friedman, Leigha Senter, Jeffrey Weitzel, Beth Karlan, Pal Moller, Ping Sun, Steven A Narod, Henry T Lynch (Collaborator), Christian Singer (Collaborator), Charis Eng (Collaborator), Gillian Mitchell (Collaborator), Tomasz Huzarski (Collaborator)Jeanna McCuaig (Collaborator), Kevin Hughes (Collaborator), Gordon Mills (Collaborator), Parviz Ghadirian (Collaborator), Andrea Eisen (Collaborator), Dawna Gilchrist (Collaborator), Joanne L Blum (Collaborator), Dana Zakalik (Collaborator), Tuya Pal (Collaborator), Mary Daly (Collaborator), Barbara Weber (Collaborator), Carrie Snyder (Collaborator), Taya Fallen (Collaborator), Albert Chudley (Collaborator), John Lunn (Collaborator), Talia Donenberg (Collaborator), Raluca N Kurz (Collaborator), Howard Saal (Collaborator), Judy Garber (Collaborator), Gad Rennert (Collaborator), Kevin Sweet (Collaborator), Ruth Gershoni-Baruch (Collaborator), Christine Rappaport (Collaborator), Edmond Lemire (Collaborator), Dominique Stoppa-Lyonnet (Collaborator), Olufunmilayo I Olopade (Collaborator), Sofia Merajver (Collaborator), Louise Bordeleau (Collaborator), Carey A Cullinane (Collaborator), Eitan Friedman (Collaborator), Wendy McKinnon (Collaborator), Marie Wood (Collaborator), Daniel Rayson (Collaborator), Wendy Meschino (Collaborator), Jane McLennan (Collaborator), Josephine Wagner Costalas (Collaborator), Robert E Reilly (Collaborator), Susan Vadaparampil (Collaborator), Kenneth Offit (Collaborator), Noah Kauff (Collaborator), Jan Klijn (Collaborator), David Euhus (Collaborator), Ava Kwong (Collaborator), Claudine Isaacs (Collaborator), Fergus Couch (Collaborator), Siranoush Manoukian (Collaborator), Tomasz Byrski (Collaborator), Christine Elser (Collaborator), Seema Panchal (Collaborator), Susan Armel (Collaborator), Sonia Nanda (Collaborator), Kelly Metcalfe (Collaborator), Aletta Poll (Collaborator), Barry Rosen (Collaborator), William D Foulkes (Collaborator), Timothy Rebbeck (Collaborator), Peter Ainsworth (Collaborator), Andre Robidoux (Collaborator), Ellen Warner (Collaborator), Lovise Maehle (Collaborator), Michael Osborne (Collaborator), Gareth Evans (Collaborator), Barbara Pasini (Collaborator), Ophira Ginsburg (Collaborator), Stephanie Cohen (Collaborator), Gorski Bohdan (Collaborator), Anna Jakubowska (Collaborator), Janice Little (Collaborator)

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

Abstract

The role of the lifetime number of ovulatory cycles has not been evaluated in the context of BRCA-associated ovarian cancer. Thus, we conducted a matched case-control study to evaluate the relationship between the cumulative number of ovulatory cycles (and contributing components) and risk of developing ovarian cancer in BRCA mutation carriers (1,329 cases and 5,267 controls). Information regarding reproductive and hormonal factors was collected from a routinely administered questionnaire. Conditional logistic regression was used to evaluate all associations. We observed a 45% reduction in the risk of developing ovarian cancer among women in the lowest vs. highest quartile of ovulatory cycles (OR = 0.55; 95% CI 0.41-0.75, p = 0.0001). Breastfeeding for more than 12 months was associated with a 38% (95% CI 0.48-0.79) and 50% (95% CI 0.29-0.84) reduction in risk among BRCA1 and BRCA2 mutation carriers, respectively. For oral contraceptive use, maximum benefit was seen with five or more years of use among BRCA1 mutation carriers (OR = 0.50; 95% CI 0.40-0.63) and three or more years for BRCA2 mutation carriers (OR = 0.42; 95% CI 0.22-0.83). Increasing parity was associated with a significant inverse trend among BRCA1 (OR = 0.87; 95% CI 0.79-0.96; p-trend = 0.005) but not BRCA2 mutation carriers (OR 0.98; 95% CI 0.81-1.19; p-trend = 0.85). A later age at menopause was associated with an increased risk in women with a BRCA1 mutation (OR trend = 1.18; 95% CI 1.03-1.35; p = 0.02). These findings support an important role of breastfeeding and oral contraceptive use for the primary prevention of ovarian cancer among women carrying BRCA mutations.

Original language	English
Journal	Journal international du cancer
Volume	137
Issue number	5
DOIs	https://doi.org/10.1002/ijc.29386
Publication status	Published - 1 Sept 2015

Keywords

BRCA1
BRCA2
ovarian cancer
ovulation

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/ijc.29386

Cite this

Kotsopoulos, J., Lubinski, J., Gronwald, J., Cybulski, C., Demsky, R., Neuhausen, S. L., Kim-Sing, C., Tung, N., Friedman, S., Senter, L., Weitzel, J., Karlan, B., Moller, P., Sun, P., Narod, S. A., Lynch, H. T., Singer, C., Eng, C., Mitchell, G., ... Little, J. (2015). Factors influencing ovulation and the risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers. Journal international du cancer, 137(5). https://doi.org/10.1002/ijc.29386

@article{34923893309642d6875f06a98fa81a63,

title = "Factors influencing ovulation and the risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers.",

abstract = "The role of the lifetime number of ovulatory cycles has not been evaluated in the context of BRCA-associated ovarian cancer. Thus, we conducted a matched case-control study to evaluate the relationship between the cumulative number of ovulatory cycles (and contributing components) and risk of developing ovarian cancer in BRCA mutation carriers (1,329 cases and 5,267 controls). Information regarding reproductive and hormonal factors was collected from a routinely administered questionnaire. Conditional logistic regression was used to evaluate all associations. We observed a 45% reduction in the risk of developing ovarian cancer among women in the lowest vs. highest quartile of ovulatory cycles (OR = 0.55; 95% CI 0.41-0.75, p = 0.0001). Breastfeeding for more than 12 months was associated with a 38% (95% CI 0.48-0.79) and 50% (95% CI 0.29-0.84) reduction in risk among BRCA1 and BRCA2 mutation carriers, respectively. For oral contraceptive use, maximum benefit was seen with five or more years of use among BRCA1 mutation carriers (OR = 0.50; 95% CI 0.40-0.63) and three or more years for BRCA2 mutation carriers (OR = 0.42; 95% CI 0.22-0.83). Increasing parity was associated with a significant inverse trend among BRCA1 (OR = 0.87; 95% CI 0.79-0.96; p-trend = 0.005) but not BRCA2 mutation carriers (OR 0.98; 95% CI 0.81-1.19; p-trend = 0.85). A later age at menopause was associated with an increased risk in women with a BRCA1 mutation (OR trend = 1.18; 95% CI 1.03-1.35; p = 0.02). These findings support an important role of breastfeeding and oral contraceptive use for the primary prevention of ovarian cancer among women carrying BRCA mutations.",

keywords = "BRCA1, BRCA2, ovarian cancer, ovulation",

author = "Joanne Kotsopoulos and Jan Lubinski and Jacek Gronwald and Cezary Cybulski and Rochelle Demsky and Neuhausen, {Susan L} and Charmaine Kim-Sing and Nadine Tung and Susan Friedman and Leigha Senter and Jeffrey Weitzel and Beth Karlan and Pal Moller and Ping Sun and Narod, {Steven A} and Lynch, {Henry T} and Christian Singer and Charis Eng and Gillian Mitchell and Tomasz Huzarski and Jeanna McCuaig and Kevin Hughes and Gordon Mills and Parviz Ghadirian and Andrea Eisen and Dawna Gilchrist and Blum, {Joanne L} and Dana Zakalik and Tuya Pal and Mary Daly and Barbara Weber and Carrie Snyder and Taya Fallen and Albert Chudley and John Lunn and Talia Donenberg and Kurz, {Raluca N} and Howard Saal and Judy Garber and Gad Rennert and Kevin Sweet and Ruth Gershoni-Baruch and Christine Rappaport and Edmond Lemire and Dominique Stoppa-Lyonnet and Olopade, {Olufunmilayo I} and Sofia Merajver and Louise Bordeleau and Cullinane, {Carey A} and Eitan Friedman and Wendy McKinnon and Marie Wood and Daniel Rayson and Wendy Meschino and Jane McLennan and Costalas, {Josephine Wagner} and Reilly, {Robert E} and Susan Vadaparampil and Kenneth Offit and Noah Kauff and Jan Klijn and David Euhus and Ava Kwong and Claudine Isaacs and Fergus Couch and Siranoush Manoukian and Tomasz Byrski and Christine Elser and Seema Panchal and Susan Armel and Sonia Nanda and Kelly Metcalfe and Aletta Poll and Barry Rosen and Foulkes, {William D} and Timothy Rebbeck and Peter Ainsworth and Andre Robidoux and Ellen Warner and Lovise Maehle and Michael Osborne and Gareth Evans and Barbara Pasini and Ophira Ginsburg and Stephanie Cohen and Gorski Bohdan and Anna Jakubowska and Janice Little",

note = "R01 CA074415, NCI NIH HHS, United States",

year = "2015",

month = sep,

day = "1",

doi = "10.1002/ijc.29386",

language = "English",

volume = "137",

journal = "Journal international du cancer",

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Kotsopoulos, J, Lubinski, J, Gronwald, J, Cybulski, C, Demsky, R, Neuhausen, SL, Kim-Sing, C, Tung, N, Friedman, S, Senter, L, Weitzel, J, Karlan, B, Moller, P, Sun, P, Narod, SA, Lynch, HT, Singer, C, Eng, C, Mitchell, G, Huzarski, T, McCuaig, J, Hughes, K, Mills, G, Ghadirian, P, Eisen, A, Gilchrist, D, Blum, JL, Zakalik, D, Pal, T, Daly, M, Weber, B, Snyder, C, Fallen, T, Chudley, A, Lunn, J, Donenberg, T, Kurz, RN, Saal, H, Garber, J, Rennert, G, Sweet, K, Gershoni-Baruch, R, Rappaport, C, Lemire, E, Stoppa-Lyonnet, D, Olopade, OI, Merajver, S, Bordeleau, L, Cullinane, CA, Friedman, E, McKinnon, W, Wood, M, Rayson, D, Meschino, W, McLennan, J, Costalas, JW, Reilly, RE, Vadaparampil, S, Offit, K, Kauff, N, Klijn, J, Euhus, D, Kwong, A, Isaacs, C, Couch, F, Manoukian, S, Byrski, T, Elser, C, Panchal, S, Armel, S, Nanda, S, Metcalfe, K, Poll, A, Rosen, B, Foulkes, WD, Rebbeck, T, Ainsworth, P, Robidoux, A, Warner, E, Maehle, L, Osborne, M, Evans, G, Pasini, B, Ginsburg, O, Cohen, S, Bohdan, G, Jakubowska, A & Little, J 2015, 'Factors influencing ovulation and the risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers.', Journal international du cancer, vol. 137, no. 5. https://doi.org/10.1002/ijc.29386

TY - JOUR

T1 - Factors influencing ovulation and the risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers.

AU - Kotsopoulos, Joanne

AU - Lubinski, Jan

AU - Gronwald, Jacek

AU - Cybulski, Cezary

AU - Demsky, Rochelle

AU - Neuhausen, Susan L

AU - Kim-Sing, Charmaine

AU - Tung, Nadine

AU - Friedman, Susan

AU - Senter, Leigha

AU - Weitzel, Jeffrey

AU - Karlan, Beth

AU - Moller, Pal

AU - Sun, Ping

AU - Narod, Steven A

A2 - Lynch, Henry T

A2 - Singer, Christian

A2 - Eng, Charis

A2 - Mitchell, Gillian

A2 - Huzarski, Tomasz

A2 - McCuaig, Jeanna

A2 - Hughes, Kevin

A2 - Mills, Gordon

A2 - Ghadirian, Parviz

A2 - Eisen, Andrea

A2 - Gilchrist, Dawna

A2 - Blum, Joanne L

A2 - Zakalik, Dana

A2 - Pal, Tuya

A2 - Daly, Mary

A2 - Weber, Barbara

A2 - Snyder, Carrie

A2 - Fallen, Taya

A2 - Chudley, Albert

A2 - Lunn, John

A2 - Donenberg, Talia

A2 - Kurz, Raluca N

A2 - Saal, Howard

A2 - Garber, Judy

A2 - Rennert, Gad

A2 - Sweet, Kevin

A2 - Gershoni-Baruch, Ruth

A2 - Rappaport, Christine

A2 - Lemire, Edmond

A2 - Stoppa-Lyonnet, Dominique

A2 - Olopade, Olufunmilayo I

A2 - Merajver, Sofia

A2 - Bordeleau, Louise

A2 - Cullinane, Carey A

A2 - Friedman, Eitan

A2 - McKinnon, Wendy

A2 - Wood, Marie

A2 - Rayson, Daniel

A2 - Meschino, Wendy

A2 - McLennan, Jane

A2 - Costalas, Josephine Wagner

A2 - Reilly, Robert E

A2 - Vadaparampil, Susan

A2 - Offit, Kenneth

A2 - Kauff, Noah

A2 - Klijn, Jan

A2 - Euhus, David

A2 - Kwong, Ava

A2 - Isaacs, Claudine

A2 - Couch, Fergus

A2 - Manoukian, Siranoush

A2 - Byrski, Tomasz

A2 - Elser, Christine

A2 - Panchal, Seema

A2 - Armel, Susan

A2 - Nanda, Sonia

A2 - Metcalfe, Kelly

A2 - Poll, Aletta

A2 - Rosen, Barry

A2 - Foulkes, William D

A2 - Rebbeck, Timothy

A2 - Ainsworth, Peter

A2 - Robidoux, Andre

A2 - Warner, Ellen

A2 - Maehle, Lovise

A2 - Osborne, Michael

A2 - Evans, Gareth

A2 - Pasini, Barbara

A2 - Ginsburg, Ophira

A2 - Cohen, Stephanie

A2 - Bohdan, Gorski

A2 - Jakubowska, Anna

A2 - Little, Janice

N1 - R01 CA074415, NCI NIH HHS, United States

PY - 2015/9/1

Y1 - 2015/9/1

N2 - The role of the lifetime number of ovulatory cycles has not been evaluated in the context of BRCA-associated ovarian cancer. Thus, we conducted a matched case-control study to evaluate the relationship between the cumulative number of ovulatory cycles (and contributing components) and risk of developing ovarian cancer in BRCA mutation carriers (1,329 cases and 5,267 controls). Information regarding reproductive and hormonal factors was collected from a routinely administered questionnaire. Conditional logistic regression was used to evaluate all associations. We observed a 45% reduction in the risk of developing ovarian cancer among women in the lowest vs. highest quartile of ovulatory cycles (OR = 0.55; 95% CI 0.41-0.75, p = 0.0001). Breastfeeding for more than 12 months was associated with a 38% (95% CI 0.48-0.79) and 50% (95% CI 0.29-0.84) reduction in risk among BRCA1 and BRCA2 mutation carriers, respectively. For oral contraceptive use, maximum benefit was seen with five or more years of use among BRCA1 mutation carriers (OR = 0.50; 95% CI 0.40-0.63) and three or more years for BRCA2 mutation carriers (OR = 0.42; 95% CI 0.22-0.83). Increasing parity was associated with a significant inverse trend among BRCA1 (OR = 0.87; 95% CI 0.79-0.96; p-trend = 0.005) but not BRCA2 mutation carriers (OR 0.98; 95% CI 0.81-1.19; p-trend = 0.85). A later age at menopause was associated with an increased risk in women with a BRCA1 mutation (OR trend = 1.18; 95% CI 1.03-1.35; p = 0.02). These findings support an important role of breastfeeding and oral contraceptive use for the primary prevention of ovarian cancer among women carrying BRCA mutations.

AB - The role of the lifetime number of ovulatory cycles has not been evaluated in the context of BRCA-associated ovarian cancer. Thus, we conducted a matched case-control study to evaluate the relationship between the cumulative number of ovulatory cycles (and contributing components) and risk of developing ovarian cancer in BRCA mutation carriers (1,329 cases and 5,267 controls). Information regarding reproductive and hormonal factors was collected from a routinely administered questionnaire. Conditional logistic regression was used to evaluate all associations. We observed a 45% reduction in the risk of developing ovarian cancer among women in the lowest vs. highest quartile of ovulatory cycles (OR = 0.55; 95% CI 0.41-0.75, p = 0.0001). Breastfeeding for more than 12 months was associated with a 38% (95% CI 0.48-0.79) and 50% (95% CI 0.29-0.84) reduction in risk among BRCA1 and BRCA2 mutation carriers, respectively. For oral contraceptive use, maximum benefit was seen with five or more years of use among BRCA1 mutation carriers (OR = 0.50; 95% CI 0.40-0.63) and three or more years for BRCA2 mutation carriers (OR = 0.42; 95% CI 0.22-0.83). Increasing parity was associated with a significant inverse trend among BRCA1 (OR = 0.87; 95% CI 0.79-0.96; p-trend = 0.005) but not BRCA2 mutation carriers (OR 0.98; 95% CI 0.81-1.19; p-trend = 0.85). A later age at menopause was associated with an increased risk in women with a BRCA1 mutation (OR trend = 1.18; 95% CI 1.03-1.35; p = 0.02). These findings support an important role of breastfeeding and oral contraceptive use for the primary prevention of ovarian cancer among women carrying BRCA mutations.

KW - BRCA1

KW - BRCA2

KW - ovarian cancer

KW - ovulation

U2 - 10.1002/ijc.29386

DO - 10.1002/ijc.29386

M3 - Article

C2 - 25482078

SN - 1097-0215

VL - 137

JO - Journal international du cancer

JF - Journal international du cancer

IS - 5

ER -

Factors influencing ovulation and the risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers.

Abstract

Keywords

UN SDGs

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