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@ARTICLE{SmithByrne:180700,
      author       = {K. Smith-Byrne and A. Cerani and F. Guida and S. Zhou and
                      A. Agudo and K. Aleksandrova and A. Barricarte and M.
                      Rodríguez-Barranco and C. H. Borchers and I. T. Gram and J.
                      Han and C. I. Amos and R. J. Hung and K. Grankvist and T. H.
                      Nøst and L. Imaz and M. D. Chirlaque-López and M.
                      Johansson and R. Kaaks$^*$ and T. Kühn$^*$ and R. M. Martin
                      and J. D. McKay and V. Pala and H. A. Robbins and T. M.
                      Sandanger and D. Schibli and M. B. Schulze and R. C. Travis
                      and P. Vineis and E. Weiderpass and P. Brennan and M.
                      Johansson and J. B. Richards},
      title        = {{C}irculating {I}sovalerylcarnitine and {L}ung {C}ancer
                      {R}isk: {E}vidence from {M}endelian {R}andomization and
                      {P}re-{D}iagnostic {B}lood {M}easurements.},
      journal      = {Cancer epidemiology, biomarkers $\&$ prevention},
      volume       = {31},
      number       = {10},
      issn         = {1055-9965},
      address      = {Philadelphia, Pa.},
      publisher    = {AACR},
      reportid     = {DKFZ-2022-01496},
      pages        = {1966-1974},
      year         = {2022},
      note         = {2022 Oct 4;31(10):1966-1974},
      abstract     = {Tobacco exposure causes 8 of 10 lung cancers, and
                      identifying additional risk factors is challenging due to
                      confounding introduced by smoking in traditional
                      observational studies.We used Mendelian randomization (MR)
                      to screen 207 metabolites for their role in lung cancer
                      predisposition using independent genome-wide-association
                      studies (GWAS) of blood metabolite levels (n =7,824) and
                      lung cancer risk (n=29,266 cases / 56,450 controls). A
                      nested case control study (656 cases and 1,309 matched
                      controls) was subsequently performed using pre-diagnostic
                      blood samples to validate MR association with lung cancer
                      incidence data from population-based cohorts (EPIC and
                      NSHDS).An MR-based scan of 207 circulating metabolites for
                      lung cancer risk identified that blood isovalerylcarnitine
                      (IVC) was associated with a decreased odds of lung cancer
                      after accounting for multiple testing (Log10-OR = 0.43,
                      $95\%$ CI: 0.29-0.63). Molar measurement of IVC in
                      pre-diagnostic blood found similar results (Log10-OR = 0.39,
                      $95\%$ CI: 0.21-0.72). Results were consistent across lung
                      cancer sub-types.Independent lines of evidence support an
                      inverse association of elevated circulating IVC with lung
                      cancer risk through a novel methodological approach that
                      integrates genetic and traditional epidemiology to
                      efficiently identify novel cancer biomarkers.Our results
                      find compelling evidence in favor of a protective role for a
                      circulating metabolite, IVC, in lung cancer aetiology. From
                      the treatment of a Mendelian disease, isovaleric acidemia,
                      we know that circulating IVC is modifiable through a
                      restricted protein diet or glycine and L-carnatine
                      supplementation. IVC may represent a modifiable and
                      inversely associated biomarker for lung cancer.},
      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:35839461},
      doi          = {10.1158/1055-9965.EPI-21-1033},
      url          = {https://inrepo02.dkfz.de/record/180700},
}