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"R01 CA063682" Dotaz Zobrazit nápovědu

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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

Qian, Frank
Autor Qian, Frank Department of Medicine, University of Chicago, Chicago, IL, USA
Rookus, Matti A
Autor Rookus, Matti A Department of Epidemiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
Leslie, Goska
Autor Leslie, Goska Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
Risch, Harvey A
Autor Risch, Harvey A Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA
Greene, Mark H
Autor Greene, Mark H Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
Aalfs, Cora M
Autor Aalfs, Cora M Department of Clinical Genetics, Amsterdam UMC, Location AMC, Amsterdam, The Netherlands
Adank, Muriel A
Autor Adank, Muriel A Family Cancer Clinic, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
Adlard, Julian
Autor Adlard, Julian Yorkshire Regional Genetics Service, Chapel Allerton Hospital, Leeds, UK
Agnarsson, Bjarni A
Autor Agnarsson, Bjarni A Department of Pathology, Landspitali University Hospital, Reykjavik, Iceland. School of Medicine, University of Iceland, Reykjavik, Iceland
Ahmed, Munaza
Autor Ahmed, Munaza North East Thames Regional Genetics Service, Great Ormond Street Hospital, London, UK

British journal of cancer. 2019 ; 121 (2) : 180-192. [pub] 20190619

Br J Cancer
ISSN 1532-1827
Medvik
Zdroj

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.

MeSH
dospělí MeSH
geny BRCA1 * MeSH
geny BRCA2 * MeSH
heterozygot * MeSH
index tělesné hmotnosti * MeSH
lidé středního věku MeSH
lidé MeSH
mendelovská randomizace * MeSH
menopauza MeSH
mutace * MeSH
nádory vaječníků etiologie genetika MeSH
proporcionální rizikové modely MeSH
senioři MeSH
tělesná výška * MeSH
Check Tag
dospělí MeSH
lidé středního věku MeSH
lidé MeSH
senioři MeSH
ženské pohlaví MeSH
Publikační typ
časopisecké články MeSH
práce podpořená grantem MeSH
Research Support, N.I.H., Extramural MeSH
Research Support, N.I.H., Intramural MeSH
Research Support, U.S. Gov't, Non-P.H.S. MeSH

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