Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers.

Frank Qian; Matti A Rookus; Goska Leslie; Harvey A Risch; Mark H Greene; Cora M Aalfs; Muriel A Adank; Julian Adlard; Bjarni A Agnarsson; Munaza Ahmed; Kristiina Aittomäki; Irene L Andrulis; Norbert Arnold; Banu K Arun; Margreet G E M Ausems; Jacopo Azzollini; Daniel Barrowdale; Julian Barwell; Javier Benitez; Katarzyna Białkowska; Valérie Bonadona; Julika Borde; Ake Borg; Angela R Bradbury; Joan Brunet; Saundra S Buys; Trinidad Caldés; Maria A Caligo; Ian Campbell; Jonathan Carter; Jocelyne Chiquette; Wendy K Chung; Kathleen B M Claes; J Margriet Collée; Marie-Agnès Collonge-Rame; Fergus J Couch; Mary B Daly; Capucine Delnatte; Orland Diez; Susan M Domchek; Cecilia M Dorfling; Jacqueline Eason; Douglas F Easton; Ros Eeles; Christoph Engel; D Gareth Evans; Laurence Faivre; Lidia Feliubadaló; Lenka Foretova; Eitan Friedman; Debra Frost; Patricia A Ganz; Judy Garber; Vanesa Garcia-Barberan; Andrea Gehrig; Gord Glendon; Andrew K Godwin; Encarna B Gómez Garcia; Ute Hamann; Jan Hauke; John L Hopper; Peter J Hulick; Evgeny N Imyanitov; Claudine Isaacs; Louise Izatt; Anna Jakubowska; Ramunas Janavicius; Esther M John; Beth Y Karlan; Carolien M Kets; Yael Laitman; Conxi Lázaro; Dominique Leroux; Jenny Lester; Fabienne Lesueur; Jennifer T Loud; Jan Lubiński; Alicja Łukomska; Lesley McGuffog; Noura Mebirouk; Hanne E J Meijers-Heijboer; Alfons Meindl; Austin Miller; Marco Montagna; Thea M Mooij; Emmanuelle Mouret-Fourme; Katherine L Nathanson; Bita Nehoray; Susan L Neuhausen; Heli Nevanlinna; Finn C Nielsen; Kenneth Offit; Edith Olah; Kai-ren Ong; Jan C Oosterwijk; Laura Ottini; Michael T Parsons; Paolo Peterlongo; Georg Pfeiler; Nisha Pradhan; Paolo Radice; Susan J Ramus; Johanna Rantala; Gad Rennert; Mark Robson; Gustavo C Rodriguez; Ritu Salani; Maren T Scheuner; Rita K Schmutzler; Payal D Shah; Lucy E Side; Jacques Simard; Christian F Singer; Doris Steinemann; Dominique Stoppa-Lyonnet; Yen Yen Tan; Manuel R Teixeira; Mary Beth Terry; Mads Thomassen; Marc Tischkowitz; Silvia Tognazzo; Amanda E Toland; Nadine Tung; Christi J van Asperen; Klaartje van Engelen; Elizabeth J van Rensburg; Laurence Venat-Bouvet; Jeroen Vierstraete; Gabriel Wagner; Lisa Walker; Jeffrey N Weitzel; Drakoulis Yannoukakos; Antonis C Antoniou; David E Goldgar; Olufunmilayo I Olopade; Georgia Chenevix-Trench; Timothy R Rebbeck; Dezheng Huo

doi:10.1038/s41416-019-0492-8

Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers.

Frank Qian, Matti A Rookus, Goska Leslie, Harvey A Risch, Mark H Greene, Cora M Aalfs, Muriel A Adank, Julian Adlard, Bjarni A Agnarsson, Munaza Ahmed, Kristiina Aittomäki, Irene L Andrulis, Norbert Arnold, Banu K Arun, Margreet G E M Ausems, Jacopo Azzollini, Daniel Barrowdale, Julian Barwell, Javier Benitez, Katarzyna BiałkowskaValérie Bonadona, Julika Borde, Ake Borg, Angela R Bradbury, Joan Brunet, Saundra S Buys, Trinidad Caldés, Maria A Caligo, Ian Campbell, Jonathan Carter, Jocelyne Chiquette, Wendy K Chung, Kathleen B M Claes, J Margriet Collée, Marie-Agnès Collonge-Rame, Fergus J Couch, Mary B Daly, Capucine Delnatte, Orland Diez, Susan M Domchek, Cecilia M Dorfling, Jacqueline Eason, Douglas F Easton, Ros Eeles, Christoph Engel, D Gareth Evans, Laurence Faivre, Lidia Feliubadaló, Lenka Foretova, Eitan Friedman, Debra Frost, Patricia A Ganz, Judy Garber, Vanesa Garcia-Barberan, Andrea Gehrig, Gord Glendon, Andrew K Godwin, Encarna B Gómez Garcia, Ute Hamann, Jan Hauke, John L Hopper, Peter J Hulick, Evgeny N Imyanitov, Claudine Isaacs, Louise Izatt, Anna Jakubowska, Ramunas Janavicius, Esther M John, Beth Y Karlan, Carolien M Kets, Yael Laitman, Conxi Lázaro, Dominique Leroux, Jenny Lester, Fabienne Lesueur, Jennifer T Loud, Jan Lubiński, Alicja Łukomska, Lesley McGuffog, Noura Mebirouk, Hanne E J Meijers-Heijboer, Alfons Meindl, Austin Miller, Marco Montagna, Thea M Mooij, Emmanuelle Mouret-Fourme, Katherine L Nathanson, Bita Nehoray, Susan L Neuhausen, Heli Nevanlinna, Finn C Nielsen, Kenneth Offit, Edith Olah, Kai-ren Ong, Jan C Oosterwijk, Laura Ottini, Michael T Parsons, Paolo Peterlongo, Georg Pfeiler, Nisha Pradhan, Paolo Radice, Susan J Ramus, Johanna Rantala, Gad Rennert, Mark Robson, Gustavo C Rodriguez, Ritu Salani, Maren T Scheuner, Rita K Schmutzler, Payal D Shah, Lucy E Side, Jacques Simard, Christian F Singer, Doris Steinemann, Dominique Stoppa-Lyonnet, Yen Yen Tan, Manuel R Teixeira, Mary Beth Terry, Mads Thomassen, Marc Tischkowitz, Silvia Tognazzo, Amanda E Toland, Nadine Tung, Christi J van Asperen, Klaartje van Engelen, Elizabeth J van Rensburg, Laurence Venat-Bouvet, Jeroen Vierstraete, Gabriel Wagner, Lisa Walker, Jeffrey N Weitzel, Drakoulis Yannoukakos, Antonis C Antoniou, David E Goldgar, Olufunmilayo I Olopade, Georgia Chenevix-Trench, Timothy R Rebbeck, Dezheng Huo

Landspitali - The National University Hospital of Iceland

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

Abstract

BACKGROUND: Height and body mass index (BMI) are associated with higher ovarian cancer risk in the general population, but whether such associations exist among BRCA1/2 mutation carriers is unknown. METHODS: We applied a Mendelian randomisation approach to examine height/BMI with ovarian cancer risk using the Consortium of Investigators for the Modifiers of BRCA1/2 (CIMBA) data set, comprising 14,676 BRCA1 and 7912 BRCA2 mutation carriers, with 2923 ovarian cancer cases. We created a height genetic score (height-GS) using 586 height-associated variants and a BMI genetic score (BMI-GS) using 93 BMI-associated variants. Associations were assessed using weighted Cox models. RESULTS: Observed height was not associated with ovarian cancer risk (hazard ratio [HR]: 1.07 per 10-cm increase in height, 95% confidence interval [CI]: 0.94-1.23). Height-GS showed similar results (HR = 1.02, 95% CI: 0.85-1.23). Higher BMI was significantly associated with increased risk in premenopausal women with HR = 1.25 (95% CI: 1.06-1.48) and HR = 1.59 (95% CI: 1.08-2.33) per 5-kg/m2 increase in observed and genetically determined BMI, respectively. No association was found for postmenopausal women. Interaction between menopausal status and BMI was significant (Pinteraction < 0.05). CONCLUSION: Our observation of a positive association between BMI and ovarian cancer risk in premenopausal BRCA1/2 mutation carriers is consistent with findings in the general population.

Original language	English
Journal	British Journal of Cancer
DOIs	https://doi.org/10.1038/s41416-019-0492-8
Publication status	Published - Jul 2019

Other keywords

Eggjastokkar
Krabbamein
Gen
Líkamsþyngdarstuðull
Líkamsþyngd
Líkamshæð
Body Mass Index
Body Height
Ovarian Neoplasms
Genes, BRCA1
Genes, BRCA2

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10.1038/s41416-019-0492-8

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Qian, F., Rookus, M. A., Leslie, G., Risch, H. A., Greene, M. H., Aalfs, C. M., Adank, M. A., Adlard, J., Agnarsson, B. A., Ahmed, M., Aittomäki, K., Andrulis, I. L., Arnold, N., Arun, B. K., Ausems, M. G. E. M., Azzollini, J., Barrowdale, D., Barwell, J., Benitez, J., ... Huo, D. (2019). Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers. British Journal of Cancer. https://doi.org/10.1038/s41416-019-0492-8

@article{ee45af534c924b71ab63c1bea76c1f30,

title = "Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers.",

abstract = "BACKGROUND: Height and body mass index (BMI) are associated with higher ovarian cancer risk in the general population, but whether such associations exist among BRCA1/2 mutation carriers is unknown. METHODS: We applied a Mendelian randomisation approach to examine height/BMI with ovarian cancer risk using the Consortium of Investigators for the Modifiers of BRCA1/2 (CIMBA) data set, comprising 14,676 BRCA1 and 7912 BRCA2 mutation carriers, with 2923 ovarian cancer cases. We created a height genetic score (height-GS) using 586 height-associated variants and a BMI genetic score (BMI-GS) using 93 BMI-associated variants. Associations were assessed using weighted Cox models. RESULTS: Observed height was not associated with ovarian cancer risk (hazard ratio [HR]: 1.07 per 10-cm increase in height, 95% confidence interval [CI]: 0.94-1.23). Height-GS showed similar results (HR = 1.02, 95% CI: 0.85-1.23). Higher BMI was significantly associated with increased risk in premenopausal women with HR = 1.25 (95% CI: 1.06-1.48) and HR = 1.59 (95% CI: 1.08-2.33) per 5-kg/m2 increase in observed and genetically determined BMI, respectively. No association was found for postmenopausal women. Interaction between menopausal status and BMI was significant (Pinteraction < 0.05). CONCLUSION: Our observation of a positive association between BMI and ovarian cancer risk in premenopausal BRCA1/2 mutation carriers is consistent with findings in the general population.",

keywords = "Eggjastokkar, Krabbamein, Gen, L{\'i}kams{\th}yngdarstu{\dh}ull, L{\'i}kams{\th}yngd, L{\'i}kamsh{\ae}{\dh}, Body Mass Index, Body Height, Ovarian Neoplasms, Genes, BRCA1, Genes, BRCA2, Eggjastokkar, Krabbamein, Gen, L{\'i}kams{\th}yngdarstu{\dh}ull, L{\'i}kams{\th}yngd, L{\'i}kamsh{\ae}{\dh}, Body Mass Index, Body Height, Ovarian Neoplasms, Genes, BRCA1, Genes, BRCA2",

author = "Frank Qian and Rookus, {Matti A} and Goska Leslie and Risch, {Harvey A} and Greene, {Mark H} and Aalfs, {Cora M} and Adank, {Muriel A} and Julian Adlard and Agnarsson, {Bjarni A} and Munaza Ahmed and Kristiina Aittom{\"a}ki and Andrulis, {Irene L} and Norbert Arnold and Arun, {Banu K} and Ausems, {Margreet G E M} and Jacopo Azzollini and Daniel Barrowdale and Julian Barwell and Javier Benitez and Katarzyna Bia{\l}kowska and Val{\'e}rie Bonadona and Julika Borde and Ake Borg and Bradbury, {Angela R} and Joan Brunet and Buys, {Saundra S} and Trinidad Cald{\'e}s and Caligo, {Maria A} and Ian Campbell and Jonathan Carter and Jocelyne Chiquette and Chung, {Wendy K} and Claes, {Kathleen B M} and Coll{\'e}e, {J Margriet} and Marie-Agn{\`e}s Collonge-Rame and Couch, {Fergus J} and Daly, {Mary B} and Capucine Delnatte and Orland Diez and Domchek, {Susan M} and Dorfling, {Cecilia M} and Jacqueline Eason and Easton, {Douglas F} and Ros Eeles and Christoph Engel and Evans, {D Gareth} and Laurence Faivre and Lidia Feliubadal{\'o} and Lenka Foretova and Eitan Friedman and Debra Frost and Ganz, {Patricia A} and Judy Garber and Vanesa Garcia-Barberan and Andrea Gehrig and Gord Glendon and Godwin, {Andrew K} and {G{\'o}mez Garcia}, {Encarna B} and Ute Hamann and Jan Hauke and Hopper, {John L} and Hulick, {Peter J} and Imyanitov, {Evgeny N} and Claudine Isaacs and Louise Izatt and Anna Jakubowska and Ramunas Janavicius and John, {Esther M} and Karlan, {Beth Y} and Kets, {Carolien M} and Yael Laitman and Conxi L{\'a}zaro and Dominique Leroux and Jenny Lester and Fabienne Lesueur and Loud, {Jennifer T} and Jan Lubi{\'n}ski and Alicja {\L}ukomska and Lesley McGuffog and Noura Mebirouk and Meijers-Heijboer, {Hanne E J} and Alfons Meindl and Austin Miller and Marco Montagna and Mooij, {Thea M} and Emmanuelle Mouret-Fourme and Nathanson, {Katherine L} and Bita Nehoray and Neuhausen, {Susan L} and Heli Nevanlinna and Nielsen, {Finn C} and Kenneth Offit and Edith Olah and Kai-ren Ong and Oosterwijk, {Jan C} and Laura Ottini and Parsons, {Michael T} and Paolo Peterlongo and Georg Pfeiler and Nisha Pradhan and Paolo Radice and Ramus, {Susan J} and Johanna Rantala and Gad Rennert and Mark Robson and Rodriguez, {Gustavo C} and Ritu Salani and Scheuner, {Maren T} and Schmutzler, {Rita K} and Shah, {Payal D} and Side, {Lucy E} and Jacques Simard and Singer, {Christian F} and Doris Steinemann and Dominique Stoppa-Lyonnet and Tan, {Yen Yen} and Teixeira, {Manuel R} and Terry, {Mary Beth} and Mads Thomassen and Marc Tischkowitz and Silvia Tognazzo and Toland, {Amanda E} and Nadine Tung and {van Asperen}, {Christi J} and {van Engelen}, Klaartje and {van Rensburg}, {Elizabeth J} and Laurence Venat-Bouvet and Jeroen Vierstraete and Gabriel Wagner and Lisa Walker and Weitzel, {Jeffrey N} and Drakoulis Yannoukakos and Antoniou, {Antonis C} and Goldgar, {David E} and Olopade, {Olufunmilayo I} and Georgia Chenevix-Trench and Rebbeck, {Timothy R} and Dezheng Huo",

year = "2019",

month = jul,

doi = "10.1038/s41416-019-0492-8",

language = "English",

journal = "British Journal of Cancer",

issn = "0007-0920",

publisher = "Nature Publishing Group",

}

Qian, F, Rookus, MA, Leslie, G, Risch, HA, Greene, MH, Aalfs, CM, Adank, MA, Adlard, J, Agnarsson, BA, Ahmed, M, Aittomäki, K, Andrulis, IL, Arnold, N, Arun, BK, Ausems, MGEM, Azzollini, J, Barrowdale, D, Barwell, J, Benitez, J, Białkowska, K, Bonadona, V, Borde, J, Borg, A, Bradbury, AR, Brunet, J, Buys, SS, Caldés, T, Caligo, MA, Campbell, I, Carter, J, Chiquette, J, Chung, WK, Claes, KBM, Collée, JM, Collonge-Rame, M-A, Couch, FJ, Daly, MB, Delnatte, C, Diez, O, Domchek, SM, Dorfling, CM, Eason, J, Easton, DF, Eeles, R, Engel, C, Evans, DG, Faivre, L, Feliubadaló, L, Foretova, L, Friedman, E, Frost, D, Ganz, PA, Garber, J, Garcia-Barberan, V, Gehrig, A, Glendon, G, Godwin, AK, Gómez Garcia, EB, Hamann, U, Hauke, J, Hopper, JL, Hulick, PJ, Imyanitov, EN, Isaacs, C, Izatt, L, Jakubowska, A, Janavicius, R, John, EM, Karlan, BY, Kets, CM, Laitman, Y, Lázaro, C, Leroux, D, Lester, J, Lesueur, F, Loud, JT, Lubiński, J, Łukomska, A, McGuffog, L, Mebirouk, N, Meijers-Heijboer, HEJ, Meindl, A, Miller, A, Montagna, M, Mooij, TM, Mouret-Fourme, E, Nathanson, KL, Nehoray, B, Neuhausen, SL, Nevanlinna, H, Nielsen, FC, Offit, K, Olah, E, Ong, K, Oosterwijk, JC, Ottini, L, Parsons, MT, Peterlongo, P, Pfeiler, G, Pradhan, N, Radice, P, Ramus, SJ, Rantala, J, Rennert, G, Robson, M, Rodriguez, GC, Salani, R, Scheuner, MT, Schmutzler, RK, Shah, PD, Side, LE, Simard, J, Singer, CF, Steinemann, D, Stoppa-Lyonnet, D, Tan, YY, Teixeira, MR, Terry, MB, Thomassen, M, Tischkowitz, M, Tognazzo, S, Toland, AE, Tung, N, van Asperen, CJ, van Engelen, K, van Rensburg, EJ, Venat-Bouvet, L, Vierstraete, J, Wagner, G, Walker, L, Weitzel, JN, Yannoukakos, D, Antoniou, AC, Goldgar, DE, Olopade, OI, Chenevix-Trench, G, Rebbeck, TR & Huo, D 2019, 'Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers.', British Journal of Cancer. https://doi.org/10.1038/s41416-019-0492-8

TY - JOUR

T1 - Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers.

AU - Qian, Frank

AU - Rookus, Matti A

AU - Leslie, Goska

AU - Risch, Harvey A

AU - Greene, Mark H

AU - Aalfs, Cora M

AU - Adank, Muriel A

AU - Adlard, Julian

AU - Agnarsson, Bjarni A

AU - Ahmed, Munaza

AU - Aittomäki, Kristiina

AU - Andrulis, Irene L

AU - Arnold, Norbert

AU - Arun, Banu K

AU - Ausems, Margreet G E M

AU - Azzollini, Jacopo

AU - Barrowdale, Daniel

AU - Barwell, Julian

AU - Benitez, Javier

AU - Białkowska, Katarzyna

AU - Bonadona, Valérie

AU - Borde, Julika

AU - Borg, Ake

AU - Bradbury, Angela R

AU - Brunet, Joan

AU - Buys, Saundra S

AU - Caldés, Trinidad

AU - Caligo, Maria A

AU - Campbell, Ian

AU - Carter, Jonathan

AU - Chiquette, Jocelyne

AU - Chung, Wendy K

AU - Claes, Kathleen B M

AU - Collée, J Margriet

AU - Collonge-Rame, Marie-Agnès

AU - Couch, Fergus J

AU - Daly, Mary B

AU - Delnatte, Capucine

AU - Diez, Orland

AU - Domchek, Susan M

AU - Dorfling, Cecilia M

AU - Eason, Jacqueline

AU - Easton, Douglas F

AU - Eeles, Ros

AU - Engel, Christoph

AU - Evans, D Gareth

AU - Faivre, Laurence

AU - Feliubadaló, Lidia

AU - Foretova, Lenka

AU - Friedman, Eitan

AU - Frost, Debra

AU - Ganz, Patricia A

AU - Garber, Judy

AU - Garcia-Barberan, Vanesa

AU - Gehrig, Andrea

AU - Glendon, Gord

AU - Godwin, Andrew K

AU - Gómez Garcia, Encarna B

AU - Hamann, Ute

AU - Hauke, Jan

AU - Hopper, John L

AU - Hulick, Peter J

AU - Imyanitov, Evgeny N

AU - Isaacs, Claudine

AU - Izatt, Louise

AU - Jakubowska, Anna

AU - Janavicius, Ramunas

AU - John, Esther M

AU - Karlan, Beth Y

AU - Kets, Carolien M

AU - Laitman, Yael

AU - Lázaro, Conxi

AU - Leroux, Dominique

AU - Lester, Jenny

AU - Lesueur, Fabienne

AU - Loud, Jennifer T

AU - Lubiński, Jan

AU - Łukomska, Alicja

AU - McGuffog, Lesley

AU - Mebirouk, Noura

AU - Meijers-Heijboer, Hanne E J

AU - Meindl, Alfons

AU - Miller, Austin

AU - Montagna, Marco

AU - Mooij, Thea M

AU - Mouret-Fourme, Emmanuelle

AU - Nathanson, Katherine L

AU - Nehoray, Bita

AU - Neuhausen, Susan L

AU - Nevanlinna, Heli

AU - Nielsen, Finn C

AU - Offit, Kenneth

AU - Olah, Edith

AU - Ong, Kai-ren

AU - Oosterwijk, Jan C

AU - Ottini, Laura

AU - Parsons, Michael T

AU - Peterlongo, Paolo

AU - Pfeiler, Georg

AU - Pradhan, Nisha

AU - Radice, Paolo

AU - Ramus, Susan J

AU - Rantala, Johanna

AU - Rennert, Gad

AU - Robson, Mark

AU - Rodriguez, Gustavo C

AU - Salani, Ritu

AU - Scheuner, Maren T

AU - Schmutzler, Rita K

AU - Shah, Payal D

AU - Side, Lucy E

AU - Simard, Jacques

AU - Singer, Christian F

AU - Steinemann, Doris

AU - Stoppa-Lyonnet, Dominique

AU - Tan, Yen Yen

AU - Teixeira, Manuel R

AU - Terry, Mary Beth

AU - Thomassen, Mads

AU - Tischkowitz, Marc

AU - Tognazzo, Silvia

AU - Toland, Amanda E

AU - Tung, Nadine

AU - van Asperen, Christi J

AU - van Engelen, Klaartje

AU - van Rensburg, Elizabeth J

AU - Venat-Bouvet, Laurence

AU - Vierstraete, Jeroen

AU - Wagner, Gabriel

AU - Walker, Lisa

AU - Weitzel, Jeffrey N

AU - Yannoukakos, Drakoulis

AU - Antoniou, Antonis C

AU - Goldgar, David E

AU - Olopade, Olufunmilayo I

AU - Chenevix-Trench, Georgia

AU - Rebbeck, Timothy R

AU - Huo, Dezheng

PY - 2019/7

Y1 - 2019/7

N2 - BACKGROUND: Height and body mass index (BMI) are associated with higher ovarian cancer risk in the general population, but whether such associations exist among BRCA1/2 mutation carriers is unknown. METHODS: We applied a Mendelian randomisation approach to examine height/BMI with ovarian cancer risk using the Consortium of Investigators for the Modifiers of BRCA1/2 (CIMBA) data set, comprising 14,676 BRCA1 and 7912 BRCA2 mutation carriers, with 2923 ovarian cancer cases. We created a height genetic score (height-GS) using 586 height-associated variants and a BMI genetic score (BMI-GS) using 93 BMI-associated variants. Associations were assessed using weighted Cox models. RESULTS: Observed height was not associated with ovarian cancer risk (hazard ratio [HR]: 1.07 per 10-cm increase in height, 95% confidence interval [CI]: 0.94-1.23). Height-GS showed similar results (HR = 1.02, 95% CI: 0.85-1.23). Higher BMI was significantly associated with increased risk in premenopausal women with HR = 1.25 (95% CI: 1.06-1.48) and HR = 1.59 (95% CI: 1.08-2.33) per 5-kg/m2 increase in observed and genetically determined BMI, respectively. No association was found for postmenopausal women. Interaction between menopausal status and BMI was significant (Pinteraction < 0.05). CONCLUSION: Our observation of a positive association between BMI and ovarian cancer risk in premenopausal BRCA1/2 mutation carriers is consistent with findings in the general population.

AB - BACKGROUND: Height and body mass index (BMI) are associated with higher ovarian cancer risk in the general population, but whether such associations exist among BRCA1/2 mutation carriers is unknown. METHODS: We applied a Mendelian randomisation approach to examine height/BMI with ovarian cancer risk using the Consortium of Investigators for the Modifiers of BRCA1/2 (CIMBA) data set, comprising 14,676 BRCA1 and 7912 BRCA2 mutation carriers, with 2923 ovarian cancer cases. We created a height genetic score (height-GS) using 586 height-associated variants and a BMI genetic score (BMI-GS) using 93 BMI-associated variants. Associations were assessed using weighted Cox models. RESULTS: Observed height was not associated with ovarian cancer risk (hazard ratio [HR]: 1.07 per 10-cm increase in height, 95% confidence interval [CI]: 0.94-1.23). Height-GS showed similar results (HR = 1.02, 95% CI: 0.85-1.23). Higher BMI was significantly associated with increased risk in premenopausal women with HR = 1.25 (95% CI: 1.06-1.48) and HR = 1.59 (95% CI: 1.08-2.33) per 5-kg/m2 increase in observed and genetically determined BMI, respectively. No association was found for postmenopausal women. Interaction between menopausal status and BMI was significant (Pinteraction < 0.05). CONCLUSION: Our observation of a positive association between BMI and ovarian cancer risk in premenopausal BRCA1/2 mutation carriers is consistent with findings in the general population.

KW - Eggjastokkar

KW - Krabbamein

KW - Gen

KW - Líkamsþyngdarstuðull

KW - Líkamsþyngd

KW - Líkamshæð

KW - Body Mass Index

KW - Body Height

KW - Ovarian Neoplasms

KW - Genes, BRCA1

KW - Genes, BRCA2

KW - Eggjastokkar

KW - Krabbamein

KW - Gen

KW - Líkamsþyngdarstuðull

KW - Líkamsþyngd

KW - Líkamshæð

KW - Body Mass Index

KW - Body Height

KW - Ovarian Neoplasms

KW - Genes, BRCA1

KW - Genes, BRCA2

U2 - 10.1038/s41416-019-0492-8

DO - 10.1038/s41416-019-0492-8

M3 - Article

C2 - 31213659

SN - 0007-0920

JO - British Journal of Cancer

JF - British Journal of Cancer

ER -

Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers.

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