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dc.contributor.authorGuo, Y
dc.contributor.authorWarren Andersen, S
dc.contributor.authorShu, X-O
dc.contributor.authorMichailidou, K
dc.contributor.authorBolla, MK
dc.contributor.authorWang, Q
dc.contributor.authorGarcia-Closas, M
dc.contributor.authorMilne, RL
dc.contributor.authorSchmidt, MK
dc.contributor.authorChang-Claude, J
dc.contributor.authorDunning, A
dc.contributor.authorBojesen, SE
dc.contributor.authorAhsan, H
dc.contributor.authorAittomäki, K
dc.contributor.authorAndrulis, IL
dc.contributor.authorAnton-Culver, H
dc.contributor.authorArndt, V
dc.contributor.authorBeckmann, MW
dc.contributor.authorBeeghly-Fadiel, A
dc.contributor.authorBenitez, J
dc.contributor.authorBogdanova, NV
dc.contributor.authorBonanni, B
dc.contributor.authorBørresen-Dale, A-L
dc.contributor.authorBrand, J
dc.contributor.authorBrauch, H
dc.contributor.authorBrenner, H
dc.contributor.authorBrüning, T
dc.contributor.authorBurwinkel, B
dc.contributor.authorCasey, G
dc.contributor.authorChenevix-Trench, G
dc.contributor.authorCouch, FJ
dc.contributor.authorCox, A
dc.contributor.authorCross, SS
dc.contributor.authorCzene, K
dc.contributor.authorDevilee, P
dc.contributor.authorDörk, T
dc.contributor.authorDumont, M
dc.contributor.authorFasching, PA
dc.contributor.authorFigueroa, J
dc.contributor.authorFlesch-Janys, D
dc.contributor.authorFletcher, O
dc.contributor.authorFlyger, H
dc.contributor.authorFostira, F
dc.contributor.authorGammon, M
dc.contributor.authorGiles, GG
dc.contributor.authorGuénel, P
dc.contributor.authorHaiman, CA
dc.contributor.authorHamann, U
dc.contributor.authorHooning, MJ
dc.contributor.authorHopper, JL
dc.contributor.authorJakubowska, A
dc.contributor.authorJasmine, F
dc.contributor.authorJenkins, M
dc.contributor.authorJohn, EM
dc.contributor.authorJohnson, N
dc.contributor.authorJones, ME
dc.contributor.authorKabisch, M
dc.contributor.authorKibriya, M
dc.contributor.authorKnight, JA
dc.contributor.authorKoppert, LB
dc.contributor.authorKosma, V-M
dc.contributor.authorKristensen, V
dc.contributor.authorLe Marchand, L
dc.contributor.authorLee, E
dc.contributor.authorLi, J
dc.contributor.authorLindblom, A
dc.contributor.authorLuben, R
dc.contributor.authorLubinski, J
dc.contributor.authorMalone, KE
dc.contributor.authorMannermaa, A
dc.contributor.authorMargolin, S
dc.contributor.authorMarme, F
dc.contributor.authorMcLean, C
dc.contributor.authorMeijers-Heijboer, H
dc.contributor.authorMeindl, A
dc.contributor.authorNeuhausen, SL
dc.contributor.authorNevanlinna, H
dc.contributor.authorNeven, P
dc.contributor.authorOlson, JE
dc.contributor.authorPerez, JIA
dc.contributor.authorPerkins, B
dc.contributor.authorPeterlongo, P
dc.contributor.authorPhillips, K-A
dc.contributor.authorPylkäs, K
dc.contributor.authorRudolph, A
dc.contributor.authorSantella, R
dc.contributor.authorSawyer, EJ
dc.contributor.authorSchmutzler, RK
dc.contributor.authorSeynaeve, C
dc.contributor.authorShah, M
dc.contributor.authorShrubsole, MJ
dc.contributor.authorSouthey, MC
dc.contributor.authorSwerdlow, AJ
dc.contributor.authorToland, AE
dc.contributor.authorTomlinson, I
dc.contributor.authorTorres, D
dc.contributor.authorTruong, T
dc.contributor.authorUrsin, G
dc.contributor.authorVan Der Luijt, RB
dc.contributor.authorVerhoef, S
dc.contributor.authorWhittemore, AS
dc.contributor.authorWinqvist, R
dc.contributor.authorZhao, H
dc.contributor.authorZhao, S
dc.contributor.authorHall, P
dc.contributor.authorSimard, J
dc.contributor.authorKraft, P
dc.contributor.authorPharoah, P
dc.contributor.authorHunter, D
dc.contributor.authorEaston, DF
dc.contributor.authorZheng, W
dc.date.accessioned2019-01-17T11:02:53Z
dc.date.issued2016-08-23
dc.identifier.citationPLoS medicine, 2016, 13 (8), pp. e1002105 - ?
dc.identifier.issn1549-1277
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3014
dc.identifier.eissn1549-1676
dc.identifier.doi10.1371/journal.pmed.1002105
dc.description.abstractBackground 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/m2 increase, 95% confidence interval [CI]: 0.56-0.75, p = 3.32 × 10-10). The associations were similar for both premenopausal (OR   =   0.44, 95% CI:0.31-0.62, p  =  9.91 × 10-8) and postmenopausal breast cancer (OR  =  0.57, 95% CI: 0.46-0.71, p  =  1.88 × 10-8). This association was replicated in the data from the DRIVE consortium (OR  =  0.72, 95% CI: 0.60-0.84, p   =   1.64 × 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.
dc.formatElectronic-eCollection
dc.format.extente1002105 - ?
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectHumans
dc.subjectBreast Neoplasms
dc.subjectGenetic Predisposition to Disease
dc.subjectBody Mass Index
dc.subjectModels, Statistical
dc.subjectRisk Factors
dc.subjectMenopause
dc.subjectPolymorphism, Single Nucleotide
dc.subjectMiddle Aged
dc.subjectEuropean Continental Ancestry Group
dc.subjectFemale
dc.subjectMendelian Randomization Analysis
dc.titleGenetically Predicted Body Mass Index and Breast Cancer Risk: Mendelian Randomization Analyses of Data from 145,000 Women of European Descent.
dc.typeJournal Article
dcterms.dateAccepted2016-06-24
rioxxterms.versionofrecord10.1371/journal.pmed.1002105
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2016-08-23
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfPLoS medicine
pubs.issue8
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Aetiological Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Functional Genetic Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Aetiological Epidemiology
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Aetiological Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Functional Genetic Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Aetiological Epidemiology
pubs.publication-statusPublished
pubs.volume13
pubs.embargo.termsNot known
icr.researchteamFunctional Genetic Epidemiologyen_US
icr.researchteamAetiological Epidemiologyen_US
dc.contributor.icrauthorFletcher, Oliviaen
dc.contributor.icrauthorJones, Michaelen
dc.contributor.icrauthorSwerdlow, Anthonyen


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