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@ARTICLE{Assi:143787,
      author       = {N. Assi and S. Rinaldi and V. Viallon and S. G. Dashti and
                      L. Dossus and A. Fournier and I. Cervenka and M. Kvaskoff
                      and R. Turzanski-Fortner$^*$ and M. Bergmann and H. Boeing
                      and S. Panico and F. Ricceri and D. Palli and R. Tumino and
                      S. Grioni and M. J. Sánchez Pérez and M.-D. Chirlaque and
                      C. Bonet and A. B. Gurrea and P. Amiano Etxezarreta and S.
                      Merino and H. B. Bueno de Mesquita and C. H. van Gils and C.
                      Onland-Moret and A. Tjønneland and K. Overvad and A.
                      Trichopoulou and G. Martimianaki and A. Karakatsani and T.
                      Key and S. Christakoudi and M. Ellingjord-Dale and K.
                      Tsilidis and E. Riboli and R. Kaaks$^*$ and M. J. Gunter and
                      P. Ferrari},
      title        = {{M}ediation analysis of the alcohol-postmenopausal breast
                      cancer relationship by sex hormones in the {EPIC} cohort.},
      journal      = {International journal of cancer},
      volume       = {146},
      number       = {3},
      issn         = {1097-0215},
      address      = {Bognor Regis},
      publisher    = {Wiley-Liss},
      reportid     = {DKFZ-2019-01356},
      pages        = {759-768},
      year         = {2020},
      note         = {2020 Feb 1;146(3):759-768},
      abstract     = {Alcohol consumption is associated with higher risk of
                      breast cancer (BC); however, the biological mechanisms
                      underlying this association are not fully elucidated,
                      particularly the extent to which this relationship is
                      mediated by sex hormone levels. Circulating concentrations
                      of estradiol, testosterone, their free fractions and
                      sex-hormone binding globulin (SHBG), were examined in 430
                      incident BC cases and 645 matched controls among
                      alcohol-consuming postmenopausal women nested within the
                      European Prospective Investigation into Cancer and
                      Nutrition. Mediation analysis was applied to assess whether
                      individual hormone levels mediated the relationship between
                      alcohol intake and BC risk. An alcohol-related hormonal
                      signature, obtained by partial least square (PLS)
                      regression, was evaluated as a potential mediator. Total
                      (TE), natural direct and natural indirect effects (NIE) were
                      estimated. Alcohol intake was positively associated with
                      overall BC risk and specifically with estrogen
                      receptor-positive tumors with respectively
                      $TE = 1.17(95\%CI:$ 1.01,1.35) and 1.36(1.08,1.70) for a
                      1-standard deviation (1-SD) increase of intake. There was no
                      evidence of mediation by sex steroids or SHBG separately
                      except for a weak indirect effect through free estradiol
                      where NIE = 1.03(1.00,1.06). However, an alcohol-related
                      hormonal signature negatively associated with SHBG and
                      positively with estradiol and testosterone was associated
                      with BC risk (odds ratio [OR] = 1.25 [1.07,1.47]) for a
                      1-SD higher PLS score, and had a statistically significant
                      NIE accounting for a mediated proportion of $24\%.$ There
                      was limited evidence of mediation of the alcohol-BC
                      association by individual sex hormones. However, a hormonal
                      signature, reflecting lower levels of SHBG and higher levels
                      of sex steroids, mediated a substantial proportion of the
                      association.},
      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:30968961},
      doi          = {10.1002/ijc.32324},
      url          = {https://inrepo02.dkfz.de/record/143787},
}