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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

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@article{21f094133d45429a9bb4e200cac863bf,
title = "Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers",
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.",
author = "Frank Qian and Rookus, {Matti A} and Goska Leslie and Risch, {Harvey A} and Greene, {Mark H} and Aalfs, {Cora M} and Adank, {Muriel A} and Julian Adlard and Agnarsson, {Bjarni A} and Munaza Ahmed and Kristiina Aittom{\"a}ki and Andrulis, {Irene L} and Norbert Arnold and Arun, {Banu K} and Ausems, {Margreet G E M} and Jacopo Azzollini and Daniel Barrowdale and Julian Barwell and Javier Benitez and Katarzyna Białkowska and Val{\'e}rie Bonadona and Julika Borde and Ake Borg and Bradbury, {Angela R} and Joan Brunet and Buys, {Saundra S} and Trinidad Cald{\'e}s and Caligo, {Maria A} and Ian Campbell and Jonathan Carter and Jocelyne Chiquette and Chung, {Wendy K} and Claes, {Kathleen B M} and Coll{\'e}e, {J Margriet} and Marie-Agn{\`e}s Collonge-Rame and Couch, {Fergus J} and Daly, {Mary B} and Capucine Delnatte and Orland Diez and Domchek, {Susan M} and Dorfling, {Cecilia M} and Jacqueline Eason and Easton, {Douglas F} and Ros Eeles and Christoph Engel and Evans, {D Gareth} and Laurence Faivre and Lidia Feliubadal{\'o} and Lenka Foretova and Nielsen, {Finn C} and {kConFab investigators}",
year = "2019",
month = "7",
doi = "10.1038/s41416-019-0492-8",
language = "English",
volume = "121",
pages = "180--192",
journal = "British Journal of Cancer",
issn = "0007-0920",
publisher = "Nature Publishing Group",
number = "2",

}

RIS

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 - 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 - Nielsen, Finn C

AU - kConFab investigators

PY - 2019/7

Y1 - 2019/7

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.

U2 - 10.1038/s41416-019-0492-8

DO - 10.1038/s41416-019-0492-8

M3 - Journal article

VL - 121

SP - 180

EP - 192

JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

IS - 2

ER -

ID: 59010527