% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Kliemann:168680,
      author       = {N. Kliemann and V. Viallon and N. Murphy and R. J. Beeken
                      and J. A. Rothwell and S. Rinaldi and N. Assi and E. H. van
                      Roekel and J. A. Schmidt and K. B. Borch and C. Agnoli and
                      A. H. Rosendahl and H. Sartor and J. M. Huerta and A.
                      Tjønneland and J. Halkjær and B. Bueno-de-Mesquita and A.
                      Gicquiau and D. Achaintre and K. Aleksandrova and M. B.
                      Schulze and A. K. Heath and K. K. Tsilidis and G. Masala and
                      S. Panico and R. Kaaks$^*$ and R. T. Fortner$^*$ and B. Van
                      Guelpen and L. Dossus and A. Scalbert and H. C. Keun and R.
                      C. Travis and M. Jenab and M. Johansson and P. Ferrari and
                      M. J. Gunter},
      title        = {{M}etabolic signatures of greater body size and their
                      associations with risk of colorectal and endometrial cancers
                      in the {E}uropean {P}rospective {I}nvestigation into
                      {C}ancer and {N}utrition.},
      journal      = {BMC medicine},
      volume       = {19},
      number       = {1},
      issn         = {1741-7015},
      address      = {Heidelberg [u.a.]},
      publisher    = {Springer},
      reportid     = {DKFZ-2021-00988},
      pages        = {101},
      year         = {2021},
      abstract     = {The mechanisms underlying the obesity-cancer relationship
                      are incompletely understood. This study aimed to
                      characterise metabolic signatures of greater body size and
                      to investigate their association with two obesity-related
                      malignancies, endometrial and colorectal cancers, and with
                      weight loss within the context of an intervention
                      study.Targeted mass spectrometry metabolomics data from 4326
                      participants enrolled in the European Prospective
                      Investigation into Cancer and Nutrition (EPIC) cohort and 17
                      individuals from a single-arm pilot weight loss intervention
                      (Intercept) were used in this analysis. Metabolic signatures
                      of body size were first determined in discovery (N = 3029)
                      and replication (N = 1297) sets among EPIC participants by
                      testing the associations between 129 metabolites and body
                      mass index (BMI), waist circumference (WC), and waist-to-hip
                      ratio (WHR) using linear regression models followed by
                      partial least squares analyses. Conditional logistic
                      regression models assessed the associations between the
                      metabolic signatures with endometrial (N = 635 cases and 648
                      controls) and colorectal (N = 423 cases and 423 controls)
                      cancer risk using nested case-control studies in EPIC.
                      Pearson correlation between changes in the metabolic
                      signatures and weight loss was tested among Intercept
                      participants.After adjustment for multiple comparisons,
                      greater BMI, WC, and WHR were associated with higher levels
                      of valine, isoleucine, glutamate, PC aa C38:3, and PC aa
                      C38:4 and with lower levels of asparagine, glutamine,
                      glycine, serine, lysoPC C17:0, lysoPC C18:1, lysoPC C18:2,
                      PC aa C42:0, PC ae C34:3, PC ae C40:5, and PC ae C42:5. The
                      metabolic signature of BMI (OR1-sd 1.50, $95\%$ CI
                      1.30-1.74), WC (OR1-sd 1.46, $95\%$ CI 1.27-1.69), and WHR
                      (OR1-sd 1.54, $95\%$ CI 1.33-1.79) were each associated with
                      endometrial cancer risk. Risk of colorectal cancer was
                      positively associated with the metabolic signature of WHR
                      (OR1-sd: 1.26, $95\%$ CI 1.07-1.49). In the Intercept study,
                      a positive correlation was observed between weight loss and
                      changes in the metabolic signatures of BMI (r = 0.5, $95\%$
                      CI 0.06-0.94, p = 0.03), WC (r = 0.5, $95\%$ CI 0.05-0.94, p
                      = 0.03), and WHR (r = 0.6, $95\%$ CI 0.32-0.87, p =
                      0.01).Obesity is associated with a distinct metabolic
                      signature comprising changes in levels of specific amino
                      acids and lipids which is positively associated with both
                      colorectal and endometrial cancer and is potentially
                      reversible following weight loss.},
      keywords     = {Cancer (Other) / Metabolomics (Other) / Obesity (Other) /
                      Weight loss (Other)},
      cin          = {C020},
      ddc          = {610},
      cid          = {I:(DE-He78)C020-20160331},
      pnm          = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
      pid          = {G:(DE-HGF)POF4-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:33926456},
      pmc          = {pmc:PMC8086283},
      doi          = {10.1186/s12916-021-01970-1},
      url          = {https://inrepo02.dkfz.de/record/168680},
}