TY - JOUR U1 - Wissenschaftlicher Artikel A1 - Ose, Jennifer A1 - Gigic, Biljana A1 - Brezina, Stefanie A1 - Lin, Tengda A1 - Peoples, Anita R. A1 - Schobert, Pauline P. A1 - Baierl, Andreas A1 - Roekel, Eline van A1 - Robinot, Nivonirina A1 - Gicquiau, Audrey A1 - Achaintre, David A1 - Scalbert, Augustin A1 - Duijnhoven, Fränzel J. B. van A1 - Holowatyj, Andreana N. A1 - Gumpenberger, Tanja A1 - Schrotz-King, Petra A1 - Ulrich, Alexis B. A1 - Ulvik, Arve A1 - Ueland, Per-Magne A1 - Weijenberg, Matty P. A1 - Habermann, Nina A1 - Keski-Rahkonen, Pekka A1 - Gsur, Andrea A1 - Kok, Dieuwertje E. A1 - Ulrich, Cornelia M. T1 - Higher Plasma Creatinine Is Associated with an Increased Risk of Death in Patients with Non-Metastatic Rectal but Not Colon Cancer: Results from an International Cohort Consortium JF - Cancers N2 - Colorectal cancer (CRC) is increasingly recognized as a heterogeneous disease. No studies have prospectively examined associations of blood metabolite concentrations with all-cause mortality in patients with colon and rectal cancer separately. Targeted metabolomics (Biocrates AbsoluteIDQ p180) and pathway analyses (MetaboAnalyst 4.0) were performed on pre-surgery collected plasma from 674 patients with non-metastasized (stage I–III) colon (n = 394) or rectal cancer (n = 283). Metabolomics data and covariate information were received from the international cohort consortium MetaboCCC. Cox proportional hazards models were computed to investigate associations of 148 metabolite levels with all-cause mortality adjusted for age, sex, tumor stage, tumor site (whenever applicable), and cohort; the false discovery rate (FDR) was used to account for multiple testing. A total of 93 patients (14%) were deceased after an average follow-up time of 4.4 years (60 patients with colon cancer and 33 patients with rectal cancer). After FDR adjustment, higher plasma creatinine was associated with a 39% increase in all-cause mortality in patients with rectal cancer. HR: 1.39, 95% CI 1.23–1.72, pFDR = 0.03; but not colon cancer: pFDR = 0.96. Creatinine is a breakdown product of creatine phosphate in muscle and may reflect changes in skeletal muscle mass. The starch and sucrose metabolisms were associated with increased all-cause mortality in colon cancer but not in rectal cancer. Genes in the starch and sucrose metabolism pathways were previously linked to worse clinical outcomes in CRC. In summary, our findings support the hypothesis that colon and rectal cancer have different etiological and clinical outcomes that need to be considered for targeted treatments. KW - all-cause mortality KW - creatinine KW - metabolites KW - colon cancer KW - rectal cancer KW - starch and sucrose pathway KW - Sterblichkeit KW - Kreatinin KW - Metabolit KW - Darmkrebs KW - Mastdarmkrebs Y1 - 2023 UN - https://nbn-resolving.org/urn:nbn:de:bsz:960-opus4-30847 SN - 2072-6694 SS - 2072-6694 U6 - https://doi.org/10.25968/opus-3084 DO - https://doi.org/10.25968/opus-3084 VL - 15 IS - 13 SP - 15 S1 - 15 ER -