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 (US) |
|---|---|
| Pages (from-to) | 180-192 |
| Number of pages | 13 |
| Journal | British journal of cancer |
| Volume | 121 |
| Issue number | 2 |
| DOIs | |
| State | Published - Jul 16 2019 |
Fingerprint
ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers. / KConFab investigators; HEBON Investigators; GEMO Study Collaborators; EMBRACE Collaborators.
In: British journal of cancer, Vol. 121, No. 2, 16.07.2019, p. 180-192.Research output: Contribution to journal › Article
}
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 - KConFab investigators
AU - HEBON Investigators
AU - GEMO Study Collaborators
AU - EMBRACE Collaborators
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
PY - 2019/7/16
Y1 - 2019/7/16
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.
UR - http://www.scopus.com/inward/record.url?scp=85067846442&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85067846442&partnerID=8YFLogxK
U2 - 10.1038/s41416-019-0492-8
DO - 10.1038/s41416-019-0492-8
M3 - Article
C2 - 31213659
AN - SCOPUS:85067846442
VL - 121
SP - 180
EP - 192
JO - British Journal of Cancer
JF - British Journal of Cancer
SN - 0007-0920
IS - 2
ER -