Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pmed.1002105
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dc.titleGenetically Predicted Body Mass Index and Breast Cancer Risk: Mendelian Randomization Analyses of Data from 145,000 Women of European Descent
dc.contributor.authorGuo Y.
dc.contributor.authorWarren Andersen S.
dc.contributor.authorShu X.-O.
dc.contributor.authorMichailidou K.
dc.contributor.authorBolla M.K.
dc.contributor.authorWang Q.
dc.contributor.authorGarcia-Closas M.
dc.contributor.authorMilne R.L.
dc.contributor.authorSchmidt M.K.
dc.contributor.authorChang-Claude J.
dc.contributor.authorDunning A.
dc.contributor.authorBojesen S.E.
dc.contributor.authorAhsan H.
dc.contributor.authorAittom�ki K.
dc.contributor.authorAndrulis I.L.
dc.contributor.authorAnton-Culver H.
dc.contributor.authorArndt V.
dc.contributor.authorBeckmann M.W.
dc.contributor.authorBeeghly-Fadiel A.
dc.contributor.authorBenitez J.
dc.contributor.authorBogdanova N.V.
dc.contributor.authorBonanni B.
dc.contributor.authorB?rresen-Dale A.-L.
dc.contributor.authorBrand J.
dc.contributor.authorBrauch H.
dc.contributor.authorBrenner H.
dc.contributor.authorBr�ning T.
dc.contributor.authorBurwinkel B.
dc.contributor.authorCasey G.
dc.contributor.authorChenevix-Trench G.
dc.contributor.authorCouch F.J.
dc.contributor.authorCox A.
dc.contributor.authorCross S.S.
dc.contributor.authorCzene K.
dc.contributor.authorDevilee P.
dc.contributor.authorD�rk T.
dc.contributor.authorDumont M.
dc.contributor.authorFasching P.A.
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 G.G.
dc.contributor.authorGu�nel P.
dc.contributor.authorHaiman C.A.
dc.contributor.authorHamann U.
dc.contributor.authorHooning M.J.
dc.contributor.authorHopper J.L.
dc.contributor.authorJakubowska A.
dc.contributor.authorJasmine F.
dc.contributor.authorJenkins M.
dc.contributor.authorJohn E.M.
dc.contributor.authorJohnson N.
dc.contributor.authorJones M.E.
dc.contributor.authorKabisch M.
dc.contributor.authorKibriya M.
dc.contributor.authorKnight J.A.
dc.contributor.authorKoppert L.B.
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 K.E.
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 S.L.
dc.contributor.authorNevanlinna H.
dc.contributor.authorNeven P.
dc.contributor.authorOlson J.E.
dc.contributor.authorPerez J.I.A.
dc.contributor.authorPerkins B.
dc.contributor.authorPeterlongo P.
dc.contributor.authorPhillips K.-A.
dc.contributor.authorPylk�s K.
dc.contributor.authorRudolph A.
dc.contributor.authorSantella R.
dc.contributor.authorSawyer E.J.
dc.contributor.authorSchmutzler R.K.
dc.contributor.authorSeynaeve C.
dc.contributor.authorShah M.
dc.contributor.authorShrubsole M.J.
dc.contributor.authorSouthey M.C.
dc.contributor.authorSwerdlow A.J.
dc.contributor.authorToland A.E.
dc.contributor.authorTomlinson I.
dc.contributor.authorTorres D.
dc.contributor.authorTruong T.
dc.contributor.authorUrsin G.
dc.contributor.authorVan Der Luijt R.B.
dc.contributor.authorVerhoef S.
dc.contributor.authorWhittemore A.S.
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 D.F.
dc.contributor.authorZheng W.
dc.date.accessioned2019-11-08T06:47:48Z
dc.date.available2019-11-08T06:47:48Z
dc.date.issued2016
dc.identifier.citationGuo Y., Warren Andersen S., Shu X.-O., Michailidou K., Bolla M.K., Wang Q., Garcia-Closas M., Milne R.L., Schmidt M.K., Chang-Claude J., Dunning A., Bojesen S.E., Ahsan H., Aittom�ki K., Andrulis I.L., Anton-Culver H., Arndt V., Beckmann M.W., Beeghly-Fadiel A., Benitez J., Bogdanova N.V., Bonanni B., B?rresen-Dale A.-L., Brand J., Brauch H., Brenner H., Br�ning T., Burwinkel B., Casey G., Chenevix-Trench G., Couch F.J., Cox A., Cross S.S., Czene K., Devilee P., D�rk T., Dumont M., Fasching P.A., Figueroa J., Flesch-Janys D., Fletcher O., Flyger H., Fostira F., Gammon M., Giles G.G., Gu�nel P., Haiman C.A., Hamann U., Hooning M.J., Hopper J.L., Jakubowska A., Jasmine F., Jenkins M., John E.M., Johnson N., Jones M.E., Kabisch M., Kibriya M., Knight J.A., Koppert L.B., Kosma V.-M., Kristensen V., Le Marchand L., Lee E., Li J., Lindblom A., Luben R., Lubinski J., Malone K.E., Mannermaa A., Margolin S., Marme F., McLean C., Meijers-Heijboer H., Meindl A., Neuhausen S.L., Nevanlinna H., Neven P., Olson J.E., Perez J.I.A., Perkins B., Peterlongo P., Phillips K.-A., Pylk�s K., Rudolph A., Santella R., Sawyer E.J., Schmutzler R.K., Seynaeve C., Shah M., Shrubsole M.J., Southey M.C., Swerdlow A.J., Toland A.E., Tomlinson I., Torres D., Truong T., Ursin G., Van Der Luijt R.B., Verhoef S., Whittemore A.S., Winqvist R., Zhao H., Zhao S., Hall P., Simard J., Kraft P., Pharoah P., Hunter D., Easton D.F., Zheng W. (2016). Genetically Predicted Body Mass Index and Breast Cancer Risk: Mendelian Randomization Analyses of Data from 145,000 Women of European Descent. PLoS Medicine 13 (8) : e1002105. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pmed.1002105
dc.identifier.issn15491277
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/161909
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. ? 2016 Guo et al.
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceUnpaywall 20191101
dc.subjectadult
dc.subjectaged
dc.subjectArticle
dc.subjectbody mass
dc.subjectbreast cancer
dc.subjectdisease association
dc.subjectenvironmental factor
dc.subjectfemale
dc.subjectgene frequency
dc.subjectgenetic heterogeneity
dc.subjectgenotyping technique
dc.subjecthuman
dc.subjectlogistic regression analysis
dc.subjectmajor clinical study
dc.subjectMendelian randomization analysis
dc.subjectmiddle aged
dc.subjectpremenopause
dc.subjectsingle nucleotide polymorphism
dc.subjectweight change
dc.subjectyoung adult
dc.subjectBreast Neoplasms
dc.subjectCaucasian
dc.subjectgenetic predisposition
dc.subjectgenetics
dc.subjectMendelian randomization analysis
dc.subjectmenopause
dc.subjectrisk factor
dc.subjectstatistical model
dc.subjectstatistics and numerical data
dc.subjectBody Mass Index
dc.subjectBreast Neoplasms
dc.subjectEuropean Continental Ancestry Group
dc.subjectFemale
dc.subjectGenetic Predisposition to Disease
dc.subjectHumans
dc.subjectMendelian Randomization Analysis
dc.subjectMenopause
dc.subjectMiddle Aged
dc.subjectModels, Statistical
dc.subjectPolymorphism, Single Nucleotide
dc.subjectRisk Factors
dc.typeArticle
dc.contributor.departmentDEPT OF SURGERY
dc.description.doi10.1371/journal.pmed.1002105
dc.description.sourcetitlePLoS Medicine
dc.description.volume13
dc.description.issue8
dc.description.pagee1002105
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