Mendelian randomisation study of height and body mass index as modifiers of ovarian cancer risk in 22,588 BRCA1 and BRCA2 mutation carriers.
Journal
British journal of cancer
ISSN: 1532-1827
Titre abrégé: Br J Cancer
Pays: England
ID NLM: 0370635
Informations de publication
Date de publication:
07 2019
07 2019
Historique:
received:
25
01
2019
accepted:
17
05
2019
revised:
03
05
2019
pubmed:
20
6
2019
medline:
17
3
2020
entrez:
20
6
2019
Statut:
ppublish
Résumé
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. 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. 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/m 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.
Sections du résumé
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/m
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.
Identifiants
pubmed: 31213659
doi: 10.1038/s41416-019-0492-8
pii: 10.1038/s41416-019-0492-8
pmc: PMC6738050
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
180-192Subventions
Organisme : NCI NIH HHS
ID : R01 CA063682
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA027469
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000124
Pays : United States
Organisme : Cancer Research UK
ID : 11174
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C1287/A 10710
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : P50 CA116201
Pays : United States
Organisme : NCI NIH HHS
ID : U19 CA148065
Pays : United States
Organisme : Cancer Research UK
ID : C1281/A12014
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : N02CP11019
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180868
Pays : United States
Organisme : NCI NIH HHS
ID : R03 CA130065
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA176785
Pays : United States
Organisme : CIHR
ID : CRN-87521
Pays : Canada
Organisme : NCI NIH HHS
ID : RC4 CA153828
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA142996
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA140323
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA125183
Pays : United States
Organisme : NCI NIH HHS
ID : UM1 CA164920
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA168524
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA161032
Pays : United States
Organisme : NCI NIH HHS
ID : P20 CA233307
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA116167
Pays : United States
Organisme : Cancer Research UK
ID : C5047/A8384
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA214545
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA128978
Pays : United States
Organisme : NCI NIH HHS
ID : U19 CA148537
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA051008
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA116167
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA037517
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM130423
Pays : United States
Organisme : Cancer Research UK (CRUK)
ID : C12292
Pays : International
Organisme : NCI NIH HHS
ID : R25 CA112486
Pays : United States
Organisme : Cancer Research UK
ID : C5047/A15007
Pays : United Kingdom
Organisme : Cancer Research UK (CRUK)
ID : A11174
Pays : International
Organisme : NCI NIH HHS
ID : N02CP65504
Pays : United States
Organisme : Cancer Research UK (CRUK)
ID : A20861
Pays : International
Organisme : Cancer Research UK
ID : 10118
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : U19 CA148112
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA149429
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA228198
Pays : United States
Organisme : Cancer Research UK
ID : C8197/A16565
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : R01 CA192393
Pays : United States
Organisme : NCI NIH HHS
ID : U10 CA180822
Pays : United States
Organisme : Medical Research Council
ID : MR/P012930/1
Pays : United Kingdom
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