Jennifer Ose1,2, Andreana N Holowatyj3,4, Johanna Nattenmüller5, Biljana Gigic6, Tengda Lin3, Caroline Himbert3,4, Nina Habermann7, David Achaintre8, Augustin Scalbert8, Pekka Keski-Rahkonen8, Jürgen Böhm3, Petra Schrotz-King9, Martin Schneider6, Alexis Ulrich6, Ellen Kampman10, Matty Weijenberg11, Andrea Gsur12, Per-Magne Ueland13, Hans-Ulrich Kauczor5, Cornelia M Ulrich14,15. 1. Huntsman Cancer Institute, Salt Lake City, UT, USA. jennifer.ose@hci.utah.edu. 2. Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA. jennifer.ose@hci.utah.edu. 3. Huntsman Cancer Institute, Salt Lake City, UT, USA. 4. Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA. 5. Diagnostic and Interventional Radiology, University Hospital of Heidelberg, Heidelberg, Germany. 6. Department of General, Visceral and Transplantation Surgery, University Hospital of Heidelberg, Heidelberg, Germany. 7. Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany. 8. International Agency Research on Cancer (IARC), Lyon, France. 9. Division of Preventive Oncology, German Cancer Research Center (DKFZ), National Center for Tumor Diseases (NCT), Heidelberg, Germany. 10. Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands. 11. Department of Epidemiology, GROW - School of Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands. 12. Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Vienna, Austria. 13. BEVITAL, Bergen, Norway. 14. Huntsman Cancer Institute, Salt Lake City, UT, USA. neli.ulrich@hci.utah.edu. 15. Department of Population Health Sciences, University of Utah, Salt Lake City, UT, USA. neli.ulrich@hci.utah.edu.
Abstract
PURPOSE: Underlying mechanisms of the relationship between body fatness and colorectal cancer remain unclear. This study investigated associations of circulating metabolites with visceral (VFA), abdominal subcutaneous (SFA), and total fat area (TFA) in colorectal cancer patients. METHODS: Pre-surgery plasma samples from 212 patients (stage I-IV) from the ColoCare Study were used to perform targeted metabolomics. VFA, SFA, and TFA were quantified by computed tomography scans. Partial correlation and linear regression analyses of VFA, SFA, and TFA with metabolites were computed and corrected for multiple testing. Cox proportional hazards were used to assess 2-year survival. RESULTS: In patients with metastatic tumors, SFA and TFA were statistically significantly inversely associated with 16 glycerophospholipids (SFA: pFDR range 0.017-0.049; TFA: pFDR range 0.029-0.048), while VFA was not. Doubling of ten of the aforementioned glycerophospholipids was associated with increased risk of death in patients with metastatic tumors, but not in patients with non-metastatic tumors (phet range: 0.00044-0.049). Doubling of PC ae C34:0 was associated with ninefold increased risk of death in metastatic tumors (Hazard Ratio [HR], 9.05; 95% confidence interval [CI] 2.17-37.80); an inverse association was observed in non-metastatic tumors (HR 0.17; 95% CI 0.04-0.87; phet = 0.00044). CONCLUSION: These data provide initial evidence that glycerophospholipids in metastatic colorectal cancer are uniquely associated with subcutaneous adiposity, and may impact overall survival.
PURPOSE: Underlying mechanisms of the relationship between body fatness and colorectal cancer remain unclear. This study investigated associations of circulating metabolites with visceral (VFA), abdominal subcutaneous (SFA), and total fat area (TFA) in colorectal cancerpatients. METHODS: Pre-surgery plasma samples from 212 patients (stage I-IV) from the ColoCare Study were used to perform targeted metabolomics. VFA, SFA, and TFA were quantified by computed tomography scans. Partial correlation and linear regression analyses of VFA, SFA, and TFA with metabolites were computed and corrected for multiple testing. Cox proportional hazards were used to assess 2-year survival. RESULTS: In patients with metastatic tumors, SFA and TFA were statistically significantly inversely associated with 16 glycerophospholipids (SFA: pFDR range 0.017-0.049; TFA: pFDR range 0.029-0.048), while VFA was not. Doubling of ten of the aforementioned glycerophospholipids was associated with increased risk of death in patients with metastatic tumors, but not in patients with non-metastatic tumors (phet range: 0.00044-0.049). Doubling of PC ae C34:0 was associated with ninefold increased risk of death in metastatic tumors (Hazard Ratio [HR], 9.05; 95% confidence interval [CI] 2.17-37.80); an inverse association was observed in non-metastatic tumors (HR 0.17; 95% CI 0.04-0.87; phet = 0.00044). CONCLUSION: These data provide initial evidence that glycerophospholipids in metastatic colorectal cancer are uniquely associated with subcutaneous adiposity, and may impact overall survival.
Authors: Andreana N Holowatyj; Mariam Haffa; Tengda Lin; Dominique Scherer; Biljana Gigic; Jennifer Ose; Christy A Warby; Caroline Himbert; Clare Abbenhardt-Martin; David Achaintre; Juergen Boehm; Kenneth M Boucher; Audrey Gicquiau; Andrea Gsur; Nina Habermann; Esther Herpel; Hans-Ulrich Kauczor; Pekka Keski-Rahkonen; Matthias Kloor; Magnus von Knebel-Doeberitz; Dieuwertje E Kok; Johanna Nattenmüller; Peter Schirmacher; Martin Schneider; Petra Schrotz-King; Thomas Simon; Per M Ueland; Richard Viskochil; Matty P Weijenberg; Augustin Scalbert; Alexis Ulrich; Laura W Bowers; Stephen D Hursting; Cornelia M Ulrich Journal: Cancer Prev Res (Phila) Date: 2020-07-12
Authors: Andreana N Holowatyj; Biljana Gigic; Christy A Warby; Jennifer Ose; Tengda Lin; Petra Schrotz-King; Cornelia M Ulrich; Jamie J Bernard Journal: Cells Date: 2021-10-06 Impact factor: 6.600
Authors: Andreana N Holowatyj; Richard Viskochil; Dominik Ose; Benjamin Tingey; Benjamin Haaland; Dalton Wilson; Mikaela Larson; Sara Feltz; Mark A Lewis; Howard Colman; Cornelia M Ulrich Journal: J Adolesc Young Adult Oncol Date: 2020-07-29 Impact factor: 2.223