File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: The genetic interplay between body mass index, breast size and breast cancer risk: a Mendelian randomization analysis

TitleThe genetic interplay between body mass index, breast size and breast cancer risk: a Mendelian randomization analysis
Authors
KeywordsBreast size
breast cancer risk
body mass index
Mendelian randomization
LDSC regression
Issue Date2019
PublisherOxford University Press. The Journal's web site is located at http://ije.oxfordjournals.org/
Citation
International Journal of Epidemiology, 2019, v. 48 n. 3, p. 781-794 How to Cite?
AbstractBackground: Evidence linking breast size to breast cancer risk has been inconsistent, and its interpretation is often hampered by confounding factors such as body mass index (BMI). Here, we used linkage disequilibrium score regression and two-sample Mendelian randomization (MR) to examine the genetic associations between BMI, breast size and breast cancer risk. Methods: Summary-level genotype data from 23andMe, Inc (breast size, n = 33 790), the Breast Cancer Association Consortium (breast cancer risk, n = 228 951) and the Genetic Investigation of ANthropometric Traits (BMI, n = 183 507) were used for our analyses. In assessing causal relationships, four complementary MR techniques [inverse variance weighted (IVW), weighted median, weighted mode and MR-Egger regression] were used to test the robustness of the results. Results: The genetic correlation (rg) estimated between BMI and breast size was high (rg = 0.50, P = 3.89x10−43). All MR methods provided consistent evidence that higher genetically predicted BMI was associated with larger breast size [odds ratio (ORIVW): 2.06 (1.80–2.35), P = 1.38x10−26] and lower overall breast cancer risk [ORIVW: 0.81 (0.74–0.89), P = 9.44x10−6]. No evidence of a relationship between genetically predicted breast size and breast cancer risk was found except when using the weighted median and weighted mode methods, and only with oestrogen receptor (ER)-negative risk. There was no evidence of reverse causality in any of the analyses conducted (P > 0.050). Conclusion: Our findings indicate a potential positive causal association between BMI and breast size and a potential negative causal association between BMI and breast cancer risk. We found no clear evidence for a direct relationship between breast size and breast cancer risk.
Persistent Identifierhttp://hdl.handle.net/10722/278655
ISSN
2019 Impact Factor: 7.707
2015 SCImago Journal Rankings: 4.381
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorOoi, BNS-
dc.contributor.authorLoh, H-
dc.contributor.authorHo, PJ-
dc.contributor.authorMine, RL-
dc.contributor.authorGiles, G-
dc.contributor.authorGao, C-
dc.contributor.authorKraft, P-
dc.contributor.authorJohn, EM-
dc.contributor.authorSwerdlow, A-
dc.contributor.authorBrenner, H-
dc.contributor.authorWu, AH-
dc.contributor.authorHaiman, C-
dc.contributor.authorEvans, DG-
dc.contributor.authorZheng, W-
dc.contributor.authorFasching, PA-
dc.contributor.authorCastelao, JE-
dc.contributor.authorKwong, A-
dc.contributor.authorShen, X-
dc.contributor.authorCzene, K-
dc.contributor.authorHall, P-
dc.contributor.authorDunning, A-
dc.contributor.authorEaston, D-
dc.contributor.authorHartman, M-
dc.contributor.authorLi, J-
dc.date.accessioned2019-10-21T02:11:35Z-
dc.date.available2019-10-21T02:11:35Z-
dc.date.issued2019-
dc.identifier.citationInternational Journal of Epidemiology, 2019, v. 48 n. 3, p. 781-794-
dc.identifier.issn0300-5771-
dc.identifier.urihttp://hdl.handle.net/10722/278655-
dc.description.abstractBackground: Evidence linking breast size to breast cancer risk has been inconsistent, and its interpretation is often hampered by confounding factors such as body mass index (BMI). Here, we used linkage disequilibrium score regression and two-sample Mendelian randomization (MR) to examine the genetic associations between BMI, breast size and breast cancer risk. Methods: Summary-level genotype data from 23andMe, Inc (breast size, n = 33 790), the Breast Cancer Association Consortium (breast cancer risk, n = 228 951) and the Genetic Investigation of ANthropometric Traits (BMI, n = 183 507) were used for our analyses. In assessing causal relationships, four complementary MR techniques [inverse variance weighted (IVW), weighted median, weighted mode and MR-Egger regression] were used to test the robustness of the results. Results: The genetic correlation (rg) estimated between BMI and breast size was high (rg = 0.50, P = 3.89x10−43). All MR methods provided consistent evidence that higher genetically predicted BMI was associated with larger breast size [odds ratio (ORIVW): 2.06 (1.80–2.35), P = 1.38x10−26] and lower overall breast cancer risk [ORIVW: 0.81 (0.74–0.89), P = 9.44x10−6]. No evidence of a relationship between genetically predicted breast size and breast cancer risk was found except when using the weighted median and weighted mode methods, and only with oestrogen receptor (ER)-negative risk. There was no evidence of reverse causality in any of the analyses conducted (P > 0.050). Conclusion: Our findings indicate a potential positive causal association between BMI and breast size and a potential negative causal association between BMI and breast cancer risk. We found no clear evidence for a direct relationship between breast size and breast cancer risk.-
dc.languageeng-
dc.publisherOxford University Press. The Journal's web site is located at http://ije.oxfordjournals.org/-
dc.relation.ispartofInternational Journal of Epidemiology-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectBreast size-
dc.subjectbreast cancer risk-
dc.subjectbody mass index-
dc.subjectMendelian randomization-
dc.subjectLDSC regression-
dc.titleThe genetic interplay between body mass index, breast size and breast cancer risk: a Mendelian randomization analysis-
dc.typeArticle-
dc.identifier.emailKwong, A: avakwong@hku.hk-
dc.identifier.authorityKwong, A=rp01734-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1093/ije/dyz124-
dc.identifier.pmid31243447-
dc.identifier.pmcidPMC6659372-
dc.identifier.scopuseid_2-s2.0-85071997122-
dc.identifier.hkuros307945-
dc.identifier.volume48-
dc.identifier.issue3-
dc.identifier.spage781-
dc.identifier.epage794-
dc.publisher.placeUnited Kingdom-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats