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@ARTICLE{EscalaGarcia:165945,
      author       = {M. Escala-Garcia and A. Morra and S. Canisius and J.
                      Chang-Claude$^*$ and S. Kar and W. Zheng and S. E. Bojesen
                      and D. Easton and P. D. P. Pharoah and M. K. Schmidt},
      title        = {{B}reast cancer risk factors and their effects on survival:
                      a {M}endelian randomisation study.},
      journal      = {BMC medicine},
      volume       = {18},
      number       = {1},
      issn         = {1741-7015},
      address      = {Heidelberg [u.a.]},
      publisher    = {Springer},
      reportid     = {DKFZ-2020-02496},
      pages        = {327},
      year         = {2020},
      abstract     = {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).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.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.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.},
      cin          = {C020},
      ddc          = {610},
      cid          = {I:(DE-He78)C020-20160331},
      pnm          = {313 - Cancer risk factors and prevention (POF3-313)},
      pid          = {G:(DE-HGF)POF3-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:33198768},
      doi          = {10.1186/s12916-020-01797-2},
      url          = {https://inrepo02.dkfz.de/record/165945},
}