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Breast cancer risk factors and their effects on survival: a Mendelian randomisation study.
Escala-Garcia, Maria; Morra, Anna; Canisius, Sander; Chang-Claude, Jenny; Kar, Siddhartha; Zheng, Wei; Bojesen, Stig E; Easton, Doug; Pharoah, Paul D P; Schmidt, Marjanka K.
Afiliação
  • Escala-Garcia M; Division of Molecular Pathology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
  • Morra A; Division of Molecular Pathology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
  • Canisius S; Division of Molecular Pathology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
  • Chang-Claude J; Division of Molecular Carcinogenesis, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
  • Kar S; Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Zheng W; University Medical Center Hamburg-Eppendorf, University Cancer Center Hamburg (UCCH), Cancer Epidemiology Group, Hamburg, Germany.
  • Bojesen SE; MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
  • Easton D; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
  • Pharoah PDP; Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
  • Schmidt MK; Copenhagen University Hospital, Copenhagen General Population Study, Herlev and Gentofte Hospital, Herlev, Denmark.
BMC Med ; 18(1): 327, 2020 11 17.
Article em En | MEDLINE | ID: mdl-33198768
BACKGROUND: Observational studies have investigated the association of risk factors with breast cancer prognosis. However, the results have been conflicting and it has been challenging to establish causality due to potential residual confounding. Using a Mendelian randomisation (MR) approach, we aimed to examine the potential causal association between breast cancer-specific survival and nine established risk factors for breast cancer: alcohol consumption, body mass index, height, physical activity, mammographic density, age at menarche or menopause, smoking, and type 2 diabetes mellitus (T2DM). METHODS: We conducted a two-sample MR analysis on data from the Breast Cancer Association Consortium (BCAC) and risk factor summary estimates from the GWAS Catalog. The BCAC data included 86,627 female patients of European ancestry with 7054 breast cancer-specific deaths during 15 years of follow-up. Of these, 59,378 were estrogen receptor (ER)-positive and 13,692 were ER-negative breast cancer patients. For the significant association, we used sensitivity analyses and a multivariable MR model. All risk factor associations were also examined in a model adjusted by other prognostic factors. RESULTS: Increased genetic liability to T2DM was significantly associated with worse breast cancer-specific survival (hazard ratio [HR] = 1.10, 95% confidence interval [CI] = 1.03-1.17, P value [P] = 0.003). There were no significant associations after multiple testing correction for any of the risk factors in the ER-status subtypes. For the reported significant association with T2DM, the sensitivity analyses did not show evidence for violation of the MR assumptions nor that the association was due to increased BMI. The association remained significant when adjusting by other prognostic factors. CONCLUSIONS: This extensive MR analysis suggests that T2DM may be causally associated with worse breast cancer-specific survival and therefore that treating T2DM may improve prognosis.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Análise da Randomização Mendeliana Tipo de estudo: Clinical_trials / Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Female / Humans Idioma: En Revista: BMC Med Assunto da revista: MEDICINA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Holanda País de publicação: Reino Unido

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Análise da Randomização Mendeliana Tipo de estudo: Clinical_trials / Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Female / Humans Idioma: En Revista: BMC Med Assunto da revista: MEDICINA Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Holanda País de publicação: Reino Unido