Guo, Yan, Andersen, Shaneda Warren, Shu, Xiao-Ou, Michailidou, Kyriaki ORCID: 0000-0001-7065-1237, Bolla, Manjeet K., Wang, Qin, Garcia-Closas, Montserrat, Milne, Roger L., Schmidt, Marjanka K., Chang-Claude, Jenny, Dunning, Allison, Bojesen, Stig E., Ahsan, Habibul, Aittomaki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker ORCID: 0000-0001-9320-8684, Beckmann, Matthias W., Beeghly-Fadiel, Alicia, Benitez, Javier, Bogdanova, Natalia V., Bonanni, Bernardo, Borresen-Dale, Anne-Lise, Brand, Judith, Brauch, Hiltrud ORCID: 0000-0001-7531-2736, Brenner, Hermann ORCID: 0000-0002-6129-1572, Bruening, Thomas, Burwinkel, Barbara, Casey, Graham, Chenevix-Trench, Georgia ORCID: 0000-0002-1878-2587, Couch, Fergus J., Cox, Angela ORCID: 0000-0002-5138-1099, Cross, Simon S., Czene, Kamila, Devilee, Peter ORCID: 0000-0002-8023-2009, Doerk, Thilo, Dumont, Martine, Fasching, Peter A., Figueroa, Jonine, Flesch-Janys, Dieter, Fletcher, Olivia ORCID: 0000-0001-9387-7116, Flyger, Henrik, Fostira, Florentia, Gammon, Marilie, Giles, Graham G., Guenel, Pascal ORCID: 0000-0002-8359-518X, Haiman, Christopher A., Hamann, Ute, Hooning, Maartje J., Hopper, John L., Jakubowska, Anna ORCID: 0000-0002-5650-0501, Jasmine, Farzana, Jenkins, Mark ORCID: 0000-0002-8964-6160, John, Esther M., Johnson, Nichola, Jones, Michael E., Kabisch, Maria, Kibriya, Muhammad, Knight, Julia A., Koppert, Linetta B., Kosma, Veli-Matti, Kristensen, Vessela, Le Marchand, Loic, Lee, Eunjung, Li, Jingmei ORCID: 0000-0001-8587-7511, Lindblom, Annika, Luben, Robert, Lubinski, Jan ORCID: 0000-0003-2931-3003, Malone, Kathi E., Mannermaa, Arto, Margolin, Sara, Marme, Frederik, McLean, Catriona, Meijers-Heijboer, Hanne, Meindl, Alfons, Neuhausen, Susan L., Nevanlinna, Heli, Neven, Patrick, Olson, Janet E., Perez, Jose I. A., Perkins, Barbara, Peterlongo, Paolo ORCID: 0000-0001-6951-6855, Phillips, Kelly-Anne, Pylkas, Katri ORCID: 0000-0002-2449-0521, Rudolph, Anja, Santella, Regina, Sawyer, Elinor J., Schmutzler, Rita K., Seynaeve, Caroline, Shah, Mitul, Shrubsole, Martha J., Southey, Melissa C., Swerdlow, Anthony J., Toland, Amanda E., Tomlinson, Ian, Torres, Diana, Truong, Therese, Ursin, Giske ORCID: 0000-0002-0835-9507, Van Der Luijt, Rob B., Verhoef, Senno, Whittemore, Alice S., Winqvist, Robert, Zhao, Hui, Zhao, Shilin, Hall, Per, Simard, Jacques, Kraft, Peter ORCID: 0000-0002-4472-8103, Pharoah, Paul ORCID: 0000-0001-8494-732X, Hunter, David, Easton, Douglas F. and Zheng, Wei ORCID: 0000-0003-1226-070X (2016). Genetically Predicted Body Mass Index and Breast Cancer Risk: Mendelian Randomization Analyses of Data from 145,000 Women of European Descent. PLos Med., 13 (8). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1549-1676

Full text not available from this repository.

Abstract

Background Observational epidemiological studies have shown that high body mass index (BMI) is associated with a reduced risk of breast cancer in premenopausal women but an increased risk in postmenopausal women. It is unclear whether this association is mediated through shared genetic or environmental factors. Methods We applied Mendelian randomization to evaluate the association between BMI and risk of breast cancer occurrence using data from two large breast cancer consortia. We created a weighted BMI genetic score comprising 84 BMI-associated genetic variants to predicted BMI. We evaluated genetically predicted BMI in association with breast cancer risk using individual-level data from the Breast Cancer Association Consortium (BCAC) (cases = 46,325, controls = 42,482). We further evaluated the association between genetically predicted BMI and breast cancer risk using summary statistics from 16,003 cases and 41,335 controls from the Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) Project. Because most studies measured BMI after cancer diagnosis, we could not conduct a parallel analysis to adequately evaluate the association of measured BMI with breast cancer risk prospectively. Results In the BCAC data, genetically predicted BMI was found to be inversely associated with breast cancer risk (odds ratio [OR] = 0.65 per 5 kg/m(2) increase, 95% confidence interval [CI]: 0.56-0.75, p = 3.32 x 10(-10)). The associations were similar for both premenopausal (OR = 0.44, 95% CI: 0.31-0.62, p = 9.91x10(-8)) and postmenopausal breast cancer (OR = 0.57, 95% CI: 0.46-0.71, p = 1.88x10(-8)). This association was replicated in the data from the DRIVE consortium (OR = 0.72, 95% CI: 0.60-0.84, p = 1.64 x 10(-7)). Single marker analyses identified 17 of the 84 BMI-associated single nucleotide polymorphisms (SNPs) in association with breast cancer risk at p < 0.05; for 16 of them, the allele associated with elevated BMI was associated with reduced breast cancer risk. Conclusions BMI predicted by genome-wide association studies (GWAS)-identified variants is inversely associated with the risk of both pre- and postmenopausal breast cancer. The reduced risk of postmenopausal breast cancer associated with genetically predicted BMI observed in this study differs from the positive association reported from studies using measured adult BMI. Understanding the reasons for this discrepancy may reveal insights into the complex relationship of genetic determinants of body weight in the etiology of breast cancer.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Guo, YanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Andersen, Shaneda WarrenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shu, Xiao-OuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Michailidou, KyriakiUNSPECIFIEDorcid.org/0000-0001-7065-1237UNSPECIFIED
Bolla, Manjeet K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wang, QinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Garcia-Closas, MontserratUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Milne, Roger L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmidt, Marjanka K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chang-Claude, JennyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dunning, AllisonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bojesen, Stig E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ahsan, HabibulUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Aittomaki, KristiinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Andrulis, Irene L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Anton-Culver, HodaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Arndt, VolkerUNSPECIFIEDorcid.org/0000-0001-9320-8684UNSPECIFIED
Beckmann, Matthias W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beeghly-Fadiel, AliciaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Benitez, JavierUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bogdanova, Natalia V.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bonanni, BernardoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Borresen-Dale, Anne-LiseUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brand, JudithUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brauch, HiltrudUNSPECIFIEDorcid.org/0000-0001-7531-2736UNSPECIFIED
Brenner, HermannUNSPECIFIEDorcid.org/0000-0002-6129-1572UNSPECIFIED
Bruening, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Burwinkel, BarbaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Casey, GrahamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chenevix-Trench, GeorgiaUNSPECIFIEDorcid.org/0000-0002-1878-2587UNSPECIFIED
Couch, Fergus J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cox, AngelaUNSPECIFIEDorcid.org/0000-0002-5138-1099UNSPECIFIED
Cross, Simon S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Czene, KamilaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Devilee, PeterUNSPECIFIEDorcid.org/0000-0002-8023-2009UNSPECIFIED
Doerk, ThiloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dumont, MartineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fasching, Peter A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Figueroa, JonineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Flesch-Janys, DieterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fletcher, OliviaUNSPECIFIEDorcid.org/0000-0001-9387-7116UNSPECIFIED
Flyger, HenrikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fostira, FlorentiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gammon, MarilieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Giles, Graham G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Guenel, PascalUNSPECIFIEDorcid.org/0000-0002-8359-518XUNSPECIFIED
Haiman, Christopher A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hamann, UteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hooning, Maartje J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hopper, John L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jakubowska, AnnaUNSPECIFIEDorcid.org/0000-0002-5650-0501UNSPECIFIED
Jasmine, FarzanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jenkins, MarkUNSPECIFIEDorcid.org/0000-0002-8964-6160UNSPECIFIED
John, Esther M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Johnson, NicholaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jones, Michael E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kabisch, MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kibriya, MuhammadUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Knight, Julia A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koppert, Linetta B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kosma, Veli-MattiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kristensen, VesselaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Le Marchand, LoicUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lee, EunjungUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Li, JingmeiUNSPECIFIEDorcid.org/0000-0001-8587-7511UNSPECIFIED
Lindblom, AnnikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Luben, RobertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lubinski, JanUNSPECIFIEDorcid.org/0000-0003-2931-3003UNSPECIFIED
Malone, Kathi E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mannermaa, ArtoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Margolin, SaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Marme, FrederikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
McLean, CatrionaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meijers-Heijboer, HanneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meindl, AlfonsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Neuhausen, Susan L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nevanlinna, HeliUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Neven, PatrickUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Olson, Janet E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Perez, Jose I. A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Perkins, BarbaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peterlongo, PaoloUNSPECIFIEDorcid.org/0000-0001-6951-6855UNSPECIFIED
Phillips, Kelly-AnneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pylkas, KatriUNSPECIFIEDorcid.org/0000-0002-2449-0521UNSPECIFIED
Rudolph, AnjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Santella, ReginaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sawyer, Elinor J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmutzler, Rita K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Seynaeve, CarolineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shah, MitulUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shrubsole, Martha J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Southey, Melissa C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Swerdlow, Anthony J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Toland, Amanda E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tomlinson, IanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Torres, DianaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Truong, ThereseUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ursin, GiskeUNSPECIFIEDorcid.org/0000-0002-0835-9507UNSPECIFIED
Van Der Luijt, Rob B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Verhoef, SennoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Whittemore, Alice S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Winqvist, RobertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhao, HuiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhao, ShilinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hall, PerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Simard, JacquesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kraft, PeterUNSPECIFIEDorcid.org/0000-0002-4472-8103UNSPECIFIED
Pharoah, PaulUNSPECIFIEDorcid.org/0000-0001-8494-732XUNSPECIFIED
Hunter, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Easton, Douglas F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zheng, WeiUNSPECIFIEDorcid.org/0000-0003-1226-070XUNSPECIFIED
URN: urn:nbn:de:hbz:38-269162
DOI: 10.1371/journal.pmed.1002105
Journal or Publication Title: PLos Med.
Volume: 13
Number: 8
Date: 2016
Publisher: PUBLIC LIBRARY SCIENCE
Place of Publication: SAN FRANCISCO
ISSN: 1549-1676
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
GENOME-WIDE ASSOCIATION; HORMONE-RECEPTOR STATUS; GENOTYPE IMPUTATION; PROSPECTIVE COHORT; FAT DISTRIBUTION; RELATIVE WEIGHT; OBESITY; LOCI; SIZE; METAANALYSISMultiple languages
Medicine, General & InternalMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/26916

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