@article{RothwellMurphyAleksandrovaetal.2020, author = {Rothwell, Joseph A. and Murphy, Neil and Aleksandrova, Krasimira and Schulze, Matthias B. and Bešević, Jelena and Kliemann, Nathalie and Jenab, Mazda and Ferrari, Pietro and Achaintre, David and Gicquiau, Audrey and Vozar, B{\´e}atrice and Scalbert, Augustin and Huybrechts, Inge and Freisling, Heinz and Prehn, Cornelia and Adamski, Jerzy and Cross, Amanda J. and Pala, Valeria Maria and Boutron-Ruault, Marie-Christine and Dahm, Christina C. and Overvad, Kim and Gram, Inger Torhild and Sandanger, Torkjel M. and Skeie, Guri and Jakszyn, Paula and Tsilidis, Kostas K. and Hughes, David J. and van Guelpen, Bethany and Bod{\´e}n, Stina and S{\´a}nchez, Maria-Jos{\´e} and Schmidt, Julie A. and Katzke, Verena and K{\"u}hn, Tilman and Colorado-Yohar, Sandra and Tumino, Rosario and Bueno-de-Mesquita, Bas and Vineis, Paolo and Masala, Giovanna and Panico, Salvatore and Eriksen, Anne Kirstine and Tj{\o}nneland, Anne and Aune, Dagfinn and Weiderpass, Elisabete and Severi, Gianluca and Chaj{\`e}s, V{\´e}ronique and Gunter, Marc J.}, title = {Metabolic signatures of healthy lifestyle patterns and colorectal cancer risk in a European cohort}, series = {Clinical gastroenterology and hepatology}, volume = {20}, journal = {Clinical gastroenterology and hepatology}, publisher = {Elsevier}, address = {New York, NY}, issn = {1542-3565}, doi = {10.1016/j.cgh.2020.11.045}, pages = {E1061 -- E1082}, year = {2020}, abstract = {BACKGROUND \& AIMS: Colorectal cancer risk can be lowered by adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) guidelines. We derived metabolic signatures of adherence to these guidelines and tested their associations with colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort. METHODS: Scores reflecting adherence to the WCRF/AICR recommendations (scale, 1-5) were calculated from participant data on weight maintenance, physical activity, diet, and alcohol among a discovery set of 5738 cancer-free European Prospective Investigation into Cancer and Nutrition participants with metabolomics data. Partial least-squares regression was used to derive fatty acid and endogenous metabolite signatures of the WCRF/AICR score in this group. In an independent set of 1608 colorectal cancer cases and matched controls, odds ratios (ORs) and 95\% CIs were calculated for colorectal cancer risk per unit increase in WCRF/AICR score and per the corresponding change in metabolic signatures using multivariable conditional logistic regression. RESULTS: Higher WCRF/AICR scores were characterized by metabolic signatures of increased odd-chain fatty acids, serine, glycine, and specific phosphatidylcholines. Signatures were inversely associated more strongly with colorectal cancer risk (fatty acids: OR, 0.51 per unit increase; 95\% CI, 0.29-0.90; endogenous metabolites: OR, 0.62 per unit change; 95\% CI, 0.50-0.78) than the WCRF/AICR score (OR, 0.93 per unit change; 95\% CI, 0.86-1.00) overall. Signature associations were stronger in male compared with female participants. CONCLUSIONS: Metabolite profiles reflecting adherence to WCRF/AICR guidelines and additional lifestyle or biological risk factors were associated with colorectal cancer. Measuring a specific panel of metabolites representative of a healthy or unhealthy lifestyle may identify strata of the population at higher risk of colorectal cancer.}, language = {en} } @article{LuReichetzederPrehnetal.2018, author = {Lu, Yong-Ping and Reichetzeder, Christoph and Prehn, Cornelia and Yin, Liang-Hong and Yun, Chen and Zeng, Shufei and Chu, Chang and Adamski, Jerzy and Hocher, Berthold}, title = {Cord blood Lysophosphatidylcholine 16:1 is positively associated with birth weight}, series = {Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry and pharmacology}, volume = {45}, journal = {Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry and pharmacology}, number = {2}, publisher = {Karger}, address = {Basel}, issn = {1015-8987}, doi = {10.1159/000487118}, pages = {614 -- 624}, year = {2018}, abstract = {Background/Aims: Impaired birth outcomes, like low birth weight, have consistently been associated with increased disease susceptibility to hypertension in later life. Alterations in the maternal or fetal metabolism might impact on fetal growth and influence birth outcomes. Discerning associations between the maternal and fetal metabolome and surrogate parameters of fetal growth could give new insight into the complex relationship between intrauterine conditions, birth outcomes, and later life disease susceptibility. Methods: Using flow injection tandem mass spectrometry, targeted metabolomics was performed in serum samples obtained from 226 mother/child pairs at delivery. Associations between neonatal birth weight and concentrations of 163 maternal and fetal metabolites were analyzed. Results: After FDR adjustment using the Benjamini-Hochberg procedure lysophosphatidylcholines (LPC) 14:0, 16:1, and 18:1 were strongly positively correlated with birth weight. In a stepwise linear regression model corrected for established confounding factors of birth weight, LPC 16: 1 showed the strongest independent association with birth weight (CI: 93.63 - 168.94; P = 6.94x10(-11)). The association with birth weight was stronger than classical confounding factors such as offspring sex (CI: - 258.81- -61.32; P = 0.002) and maternal smoking during pregnancy (CI: -298.74 - -29.51; P = 0.017). Conclusions: After correction for multiple testing and adjustment for potential confounders, LPC 16:1 showed a very strong and independent association with birth weight. The underlying molecular mechanisms linking fetal LPCs with birth weight need to be addressed in future studies. (c) 2018 The Author(s) Published by S. Karger AG, Basel}, language = {en} } @article{LuReichetzederPrehnetal.2018, author = {Lu, Yong-Ping and Reichetzeder, Christoph and Prehn, Cornelia and von Websky, Karoline and Slowinski, Torsten and Chen, You-Peng and Yin, Liang-Hong and Kleuser, Burkhard and Yang, Xue-Song and Adamski, Jerzy and Hocher, Berthold}, title = {Fetal serum metabolites are independently associated with Gestational diabetes mellitus}, series = {Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry and pharmacology}, volume = {45}, journal = {Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry and pharmacology}, number = {2}, publisher = {Karger}, address = {Basel}, issn = {1015-8987}, doi = {10.1159/000487119}, pages = {625 -- 638}, year = {2018}, abstract = {Background/Aims: Gestational diabetes (GDM) might be associated with alterations in the metabolomic profile of affected mothers and their offspring. Until now, there is a paucity of studies that investigated both, the maternal and the fetal serum metabolome in the setting of GDM. Mounting evidence suggests that the fetus is not just passively affected by gestational disease but might play an active role in it. Metabolomic studies performed in maternal blood and fetal cord blood could help to better discern distinct fetal from maternal disease interactions. Methods: At the time of birth, serum samples from mothers and newborns (cord blood samples) were collected and screened for 163 metabolites utilizing tandem mass spectrometry. The cohort consisted of 412 mother/child pairs, including 31 cases of maternal GDM. Results: An initial non-adjusted analysis showed that eight metabolites in the maternal blood and 54 metabolites in the cord blood were associated with GDM. After Benjamini-Hochberg (BH) procedure and adjustment for confounding factors for GDM, fetal phosphatidylcholine acyl-alkyl C 32:1 and proline still showed an independent association with GDM. Conclusions: This study found metabolites in cord blood which were associated with GDM, even after adjustment for established risk factors of GDM. To the best of our knowledge, this is the first study demonstrating an independent association between fetal serum metabolites and maternal GDM. Our findings might suggest a potential effect of the fetal metabolome on maternal GDM. (c) 2018 The Author(s) Published by S. Karger AG, Basel}, language = {en} }