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Article: Height and Body Mass Index as Modifiers of Breast Cancer Risk in BRCA1/2 Mutation Carriers: A Mendelian Randomization Study

TitleHeight and Body Mass Index as Modifiers of Breast Cancer Risk in BRCA1/2 Mutation Carriers: A Mendelian Randomization Study
Authors
Issue Date2019
PublisherOxford University Press. The Journal's web site is located at http://jncicancerspectrum.oxfordjournals.org/
Citation
JNCI: Journal of the National Cancer Institute, 2019, v. 111, p. 350-364 How to Cite?
AbstractBACKGROUND: BRCA1/2 mutations confer high lifetime risk of breast cancer, although other factors may modify this risk. Whether height or body mass index (BMI) modifies breast cancer risk in BRCA1/2 mutation carriers remains unclear. METHODS: We used Mendelian randomization approaches to evaluate the association of height and BMI on breast cancer risk, using data from the Consortium of Investigators of Modifiers of BRCA1/2 with 14 676 BRCA1 and 7912 BRCA2 mutation carriers, including 11 451 cases of breast cancer. We created a height genetic score using 586 height-associated variants and a BMI genetic score using 93 BMI-associated variants. We examined both observed and genetically determined height and BMI with breast cancer risk using weighted Cox models. All statistical tests were two-sided. RESULTS: Observed height was positively associated with breast cancer risk (HR = 1.09 per 10 cm increase, 95% confidence interval [CI] = 1.0 to 1.17; P = 1.17). Height genetic score was positively associated with breast cancer, although this was not statistically significant (per 10 cm increase in genetically predicted height, HR = 1.04, 95% CI = 0.93 to 1.17; P = .47). Observed BMI was inversely associated with breast cancer risk (per 5 kg/m2 increase, HR = 0.94, 95% CI = 0.90 to 0.98; P = .007). BMI genetic score was also inversely associated with breast cancer risk (per 5 kg/m2 increase in genetically predicted BMI, HR = 0.87, 95% CI = 0.76 to 0.98; P = .02). BMI was primarily associated with premenopausal breast cancer. CONCLUSION: Height is associated with overall breast cancer and BMI is associated with premenopausal breast cancer in BRCA1/2 mutation carriers. Incorporating height and BMI, particularly genetic score, into risk assessment may improve cancer management.
Persistent Identifierhttp://hdl.handle.net/10722/270111
ISSN
2017 Impact Factor: 11.238
2015 SCImago Journal Rankings: 6.192
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorQian, F-
dc.contributor.authorWang, S-
dc.contributor.authorMitchell, J-
dc.contributor.authorMcGuffog, L-
dc.contributor.authorBarrowdale, D-
dc.contributor.authorLesile, G-
dc.contributor.authorOosterwijk, JC-
dc.contributor.authorChung, WK-
dc.contributor.authorEvans, DG-
dc.contributor.authorEngel, C-
dc.contributor.authorKast, K-
dc.contributor.authorAalfs, CM-
dc.contributor.authorAdank, MA-
dc.contributor.authorAdlard, J-
dc.contributor.authorAgnarsson, BA-
dc.contributor.authorAittomaki, K-
dc.contributor.authorAlducci, E-
dc.contributor.authorAndrulis, IL-
dc.contributor.authorArun, BK-
dc.contributor.authorAusems, MGEM-
dc.contributor.authorAzzollini, J-
dc.contributor.authorBarouk-Simonet, E-
dc.contributor.authorBarwell, J-
dc.contributor.authorBelotti, M-
dc.contributor.authorBenitez, A-
dc.contributor.authorBerger, A-
dc.contributor.authorBorg, A-
dc.contributor.authorBradbury, AR-
dc.contributor.authorBrunet, J-
dc.contributor.authorBuys, SS-
dc.contributor.authorCaldes, T-
dc.contributor.authorCaligo, MA-
dc.contributor.authorCampbell, I-
dc.contributor.authorCaputo, SM-
dc.contributor.authorChiquette, J-
dc.contributor.authorClaes, KBM-
dc.contributor.authorMargriet Collée, J-
dc.contributor.authorCouch, FJ-
dc.contributor.authorCoupier, I-
dc.contributor.authorDaly, MB-
dc.contributor.authorDavidson, R-
dc.contributor.authorDiez, O-
dc.contributor.authorDomchek, SM-
dc.contributor.authorDonaldson, A-
dc.contributor.authorDorfling, CM-
dc.contributor.authorEeles, R-
dc.contributor.authorFeliubadaló, L-
dc.contributor.authorForetova, L-
dc.contributor.authorFowler, J-
dc.contributor.authorFriedman, E-
dc.contributor.authorFrost, D-
dc.contributor.authorGanz, PA-
dc.contributor.authorGarber, J-
dc.contributor.authorGarcia-Barberan, V-
dc.contributor.authorGlendon, G-
dc.contributor.authorGodwin, AK-
dc.contributor.authorGómez Garcia, EB-
dc.contributor.authorGonwald, J-
dc.contributor.authorHahnen, E-
dc.contributor.authorKwong, A-
dc.date.accessioned2019-05-20T05:09:47Z-
dc.date.available2019-05-20T05:09:47Z-
dc.date.issued2019-
dc.identifier.citationJNCI: Journal of the National Cancer Institute, 2019, v. 111, p. 350-364-
dc.identifier.issn0027-8874-
dc.identifier.urihttp://hdl.handle.net/10722/270111-
dc.description.abstractBACKGROUND: BRCA1/2 mutations confer high lifetime risk of breast cancer, although other factors may modify this risk. Whether height or body mass index (BMI) modifies breast cancer risk in BRCA1/2 mutation carriers remains unclear. METHODS: We used Mendelian randomization approaches to evaluate the association of height and BMI on breast cancer risk, using data from the Consortium of Investigators of Modifiers of BRCA1/2 with 14 676 BRCA1 and 7912 BRCA2 mutation carriers, including 11 451 cases of breast cancer. We created a height genetic score using 586 height-associated variants and a BMI genetic score using 93 BMI-associated variants. We examined both observed and genetically determined height and BMI with breast cancer risk using weighted Cox models. All statistical tests were two-sided. RESULTS: Observed height was positively associated with breast cancer risk (HR = 1.09 per 10 cm increase, 95% confidence interval [CI] = 1.0 to 1.17; P = 1.17). Height genetic score was positively associated with breast cancer, although this was not statistically significant (per 10 cm increase in genetically predicted height, HR = 1.04, 95% CI = 0.93 to 1.17; P = .47). Observed BMI was inversely associated with breast cancer risk (per 5 kg/m2 increase, HR = 0.94, 95% CI = 0.90 to 0.98; P = .007). BMI genetic score was also inversely associated with breast cancer risk (per 5 kg/m2 increase in genetically predicted BMI, HR = 0.87, 95% CI = 0.76 to 0.98; P = .02). BMI was primarily associated with premenopausal breast cancer. CONCLUSION: Height is associated with overall breast cancer and BMI is associated with premenopausal breast cancer in BRCA1/2 mutation carriers. Incorporating height and BMI, particularly genetic score, into risk assessment may improve cancer management.-
dc.languageeng-
dc.publisherOxford University Press. The Journal's web site is located at http://jncicancerspectrum.oxfordjournals.org/-
dc.relation.ispartofJNCI: Journal of the National Cancer Institute-
dc.rightsPre-print: Journal Title] ©: [year] [owner as specified on the article] Published by Oxford University Press [on behalf of xxxxxx]. All rights reserved. Pre-print (Once an article is published, preprint notice should be amended to): This is an electronic version of an article published in [include the complete citation information for the final version of the Article as published in the print edition of the Journal.] Post-print: This is a pre-copy-editing, author-produced PDF of an article accepted for publication in [insert journal title] following peer review. The definitive publisher-authenticated version [insert complete citation information here] is available online at: xxxxxxx [insert URL that the author will receive upon publication here]. -
dc.titleHeight and Body Mass Index as Modifiers of Breast Cancer Risk in BRCA1/2 Mutation Carriers: A Mendelian Randomization Study-
dc.typeArticle-
dc.identifier.emailKwong, A: avakwong@hku.hk-
dc.identifier.authorityKwong, A=rp01734-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1093/jnci/djy132-
dc.identifier.pmcidPMC6449171-
dc.identifier.hkuros297850-
dc.identifier.volume111-
dc.identifier.spage350-
dc.identifier.epage364-
dc.publisher.placeUnited Kingdom-

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