| Title: |
Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers. |
| 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 |
| Contributors: |
Eeles, Rosalind |
| Publisher Information: |
SPRINGERNATURE |
| Publication Year: |
2019 |
| Collection: |
The Institute of Cancer Research (ICR): Publications Repository |
| Subject Terms: |
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; BRCA2; Adult; Aged; Middle Aged; Female; Mendelian Randomization Analysis |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
Print-Electronic; 192; application/pdf |
| Language: |
English |
| ISSN: |
1532-1827; 0007-0920 |
| Relation: |
British journal of cancer, 2019, 121 (2), pp. 180 - 192; https://repository.icr.ac.uk/handle/internal/3340 |
| Availability: |
https://repository.icr.ac.uk/handle/internal/3340 |
| Rights: |
https://creativecommons.org/licenses/by/4.0 |
| Accession Number: |
edsbas.3C87F331 |
| Database: |
BASE |