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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Date
2019-07-16ICR Author
Author
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,
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
KConFab Investigators
HEBON Investigators
GEMO Study Collaborators
EMBRACE Collaborators
CIMBA
Humans
Ovarian Neoplasms
Body Mass Index
Body Height
Proportional Hazards Models
Menopause
Heterozygote
Mutation
Genes, BRCA1
Genes, BRCA2
Adult
Aged
Middle Aged
Female
Mendelian Randomization Analysis
Research team
Oncogenetics
Language
eng
Date accepted
2019-05-17
License start date
2019-07
Citation
British journal of cancer, 2019, 121 (2), pp. 180 - 192
Publisher
NATURE PUBLISHING GROUP