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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ICR Authors
Authors
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-R
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
KConFab Investigators,
HEBON Investigators,
GEMO Study Collaborators,
EMBRACE Collaborators,
Antoniou, AC
Goldgar, DE
Olopade, OI
Chenevix-Trench, G
Rebbeck, TR
Huo, D
CIMBA,
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-R
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
KConFab Investigators,
HEBON Investigators,
GEMO Study Collaborators,
EMBRACE Collaborators,
Antoniou, AC
Goldgar, DE
Olopade, OI
Chenevix-Trench, G
Rebbeck, TR
Huo, D
CIMBA,
Document Type
Journal Article
Date
2019-07-16
Date Accepted
2019-05-17
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.
Citation
British journal of cancer, 2019, 121 (2), pp. 180 - 192
Source Title
Publisher
SPRINGERNATURE
ISSN
0007-0920
eISSN
1532-1827
Research Team
Oncogenetics