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@ARTICLE{Dimou:143866,
      author       = {N. L. Dimou and N. Papadimitriou and D. Gill and S.
                      Christakoudi and N. Murphy and M. J. Gunter and R. C. Travis
                      and T. J. Key and R. T. Fortner$^*$ and P. C. Haycock and S.
                      J. Lewis and K. Muir and R. M. Martin and K. K. Tsilidis},
      title        = {{S}ex hormone binding globulin and risk of breast cancer: a
                      {M}endelian randomization study.},
      journal      = {International journal of epidemiology},
      volume       = {48},
      number       = {3},
      issn         = {1464-3685},
      address      = {Oxford},
      publisher    = {Oxford Univ. Press},
      reportid     = {DKFZ-2019-01428},
      pages        = {807-816},
      year         = {2019},
      abstract     = {There are observational data suggesting an inverse
                      association between circulating concentrations of sex
                      hormone binding globulin (SHBG) and risk of postmenopausal
                      breast cancer. However, causality is uncertain and few
                      studies have investigated this association by tumour
                      receptor status. We aimed to investigate these associations
                      under the causal framework of Mendelian randomization
                      (MR).We used summary association estimates extracted from
                      published genome-wide association study (GWAS) meta-analyses
                      for SHBG and breast cancer, to perform two-sample MR
                      analyses. Summary statistics were available for 122 977
                      overall breast cancer cases, of which 69 501 were estrogen
                      receptor positive (ER+ve) and 21 468 were ER-ve, and
                      105 974 controls. To control for potential horizontal
                      pleiotropy acting via body mass index (BMI), we performed
                      multivariable inverse-variance weighted (IVW) MR as the main
                      analysis, with the robustness of this approach further
                      tested in sensitivity analyses.The multivariable IVW MR
                      analysis indicated a lower risk of overall (odds ratio [OR]:
                      0.94; $95\%$ confidence interval [CI]: 0.90, 0.98; P: 0.006)
                      and ER+ve (OR: $0.92; 95\%$ CI: 0.87, 0.97; P: 0.003)
                      breast cancer, and a higher risk of ER-ve disease (OR: 1.09;
                      $95\%$ CI: 1.00, 1.18; P: 0.047) per 25 nmol/L higher
                      SHBG levels. Sensitivity analyses were consistent with the
                      findings of the main analysis.We corroborated the previous
                      literature evidence coming from observational studies for a
                      potentially causal inverse association between SHBG
                      concentrations and risk of ER+ve breast cancer, but our
                      findings also suggested a potential novel positive
                      association with ER-ve disease that warrants further
                      investigation, given the low prior probability of being
                      true.},
      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:31143958},
      doi          = {10.1093/ije/dyz107},
      url          = {https://inrepo02.dkfz.de/record/143866},
}