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

(2019) BRITISH JOURNAL OF CANCER. 121(2). p.180-192
Author
Organization
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/m(2) increase in observed and genetically determined BMI, respectively. No association was found for postmenopausal women. Interaction between menopausal status and BMI was significant (P-interaction < 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
ANTHROPOMETRIC MEASURES, BREAST, ASSOCIATION, OBESITY, COHORT, INFERTILITY, MORTALITY, PROGESTIN, APOPTOSIS, PATHWAYS

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MLA
Qian, Frank et al. “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 121.2 (2019): 180–192. Print.
APA
Qian, F., Rookus, M. A., Leslie, G., Risch, H. A., Greene, M. H., Aalfs, C. M., Adank, M. A., et al. (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, 121(2), 180–192.
Chicago author-date
Qian, Frank, Matti A Rookus, Goska Leslie, Harvey A Risch, Mark H Greene, Cora M Aalfs, Muriel A Adank, et al. 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 121 (2): 180–192.
Chicago author-date (all authors)
Qian, Frank, 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 GEM 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 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 EJ 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, and Dezheng Huo. 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 121 (2): 180–192.
Vancouver
1.
Qian F, Rookus MA, Leslie G, Risch HA, Greene MH, Aalfs CM, et al. 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. 2019;121(2):180–92.
IEEE
[1]
F. Qian et al., “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, vol. 121, no. 2, pp. 180–192, 2019.
@article{8622899,
  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/m(2) increase in observed and genetically determined BMI, respectively. No association was found for postmenopausal women. Interaction between menopausal status and BMI was significant (P-interaction < 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.},
  author       = {Qian, Frank and Rookus, Matti A and Leslie, Goska and Risch, Harvey A and Greene, Mark H and Aalfs, Cora M and Adank, Muriel A and Adlard, Julian and Agnarsson, Bjarni A and Ahmed, Munaza and Aittomäki, Kristiina and Andrulis, Irene L and Arnold, Norbert and Arun, Banu K and Ausems, Margreet GEM and Azzollini, Jacopo and Barrowdale, Daniel and Barwell, Julian and Benitez, Javier and Białkowska, Katarzyna and Bonadona, Valérie and Borde, Julika and Borg, Ake and Bradbury, Angela R and Brunet, Joan and Buys, Saundra S and Caldés, Trinidad and Caligo, Maria A and Campbell, Ian and Carter, Jonathan and Chiquette, Jocelyne and Chung, Wendy K and Claes, Kathleen and Collée, J Margriet and Collonge-Rame, Marie-Agnès and Couch, Fergus J and Daly, Mary B and Delnatte, Capucine and Diez, Orland and Domchek, Susan M and Dorfling, Cecilia M and Eason, Jacqueline and Easton, Douglas F and Eeles, Ros and Engel, Christoph and Evans, D Gareth and Faivre, Laurence and Feliubadaló, Lidia and Foretova, Lenka and Friedman, Eitan and Frost, Debra and Ganz, Patricia A and Garber, Judy and Garcia-Barberan, Vanesa and Gehrig, Andrea and Glendon, Gord and Godwin, Andrew K and Gómez Garcia, Encarna B and Hamann, Ute and Hauke, Jan and Hopper, John L and Hulick, Peter J and Imyanitov, Evgeny N and Isaacs, Claudine and Izatt, Louise and Jakubowska, Anna and Janavicius, Ramunas and John, Esther M and Karlan, Beth Y and Kets, Carolien M and Laitman, Yael and Lázaro, Conxi and Leroux, Dominique and Lester, Jenny and Lesueur, Fabienne and Loud, Jennifer T and Lubiński, Jan and Łukomska, Alicja and McGuffog, Lesley and Mebirouk, Noura and Meijers-Heijboer, Hanne EJ and Meindl, Alfons and Miller, Austin and Montagna, Marco and Mooij, Thea M and Mouret-Fourme, Emmanuelle and Nathanson, Katherine L and Nehoray, Bita and Neuhausen, Susan L and Nevanlinna, Heli and Nielsen, Finn C and Offit, Kenneth and Olah, Edith and Ong, Kai-ren and Oosterwijk, Jan C and Ottini, Laura and Parsons, Michael T and Peterlongo, Paolo and Pfeiler, Georg and Pradhan, Nisha and Radice, Paolo and Ramus, Susan J and Rantala, Johanna and Rennert, Gad and Robson, Mark and Rodriguez, Gustavo C and Salani, Ritu and Scheuner, Maren T and Schmutzler, Rita K and Shah, Payal D and Side, Lucy E and Simard, Jacques and Singer, Christian F and Steinemann, Doris and Stoppa-Lyonnet, Dominique and Tan, Yen Yen and Teixeira, Manuel R and Terry, Mary Beth and Thomassen, Mads and Tischkowitz, Marc and Tognazzo, Silvia and Toland, Amanda E and Tung, Nadine and van Asperen, Christi J and van Engelen, Klaartje and van Rensburg, Elizabeth J and Venat-Bouvet, Laurence and Vierstraete, Jeroen and Wagner, Gabriel and Walker, Lisa and Weitzel, Jeffrey N and Yannoukakos, Drakoulis and Antoniou, Antonis C and Goldgar, David E and Olopade, Olufunmilayo I and Chenevix-Trench, Georgia and Rebbeck, Timothy R and Huo, Dezheng},
  issn         = {0007-0920},
  journal      = {BRITISH JOURNAL OF CANCER},
  keywords     = {ANTHROPOMETRIC MEASURES,BREAST,ASSOCIATION,OBESITY,COHORT,INFERTILITY,MORTALITY,PROGESTIN,APOPTOSIS,PATHWAYS},
  language     = {eng},
  number       = {2},
  pages        = {180--192},
  title        = {Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers},
  url          = {http://dx.doi.org/10.1038/s41416-019-0492-8},
  volume       = {121},
  year         = {2019},
}

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