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1. Coffee consumption is associated with a reduced risk of colorectal cancer recurrence and all-cause mortality.

Author: Oyelere, A.M., Kok, D.E., Bos, D., Gunter, M.J., Ferrari, Pietro, Keski-Rahkonen, P., Wilt, J.H.W. de, Halteren, H.K. van, Kouwenhoven, E.A., Duijnhoven, F. J. B. van, Kampman, E., Oyelere, A.M., Kok, D.E., Bos, D., Gunter, M.J., Ferrari, Pietro, Keski-Rahkonen, P., Wilt, J.H.W. de, Halteren, H.K. van, Kouwenhoven, E.A., Duijnhoven, F. J. B. van, and Kampman, E.
Abstract: Contains fulltext : 306358.pdf (Publisher’s version ) (Open Access), Coffee consumption has been associated with a reduced risk of developing colorectal cancer (CRC). However, it is not clear whether coffee consumption is related to CRC progression. Hence, we assessed the association of coffee consumption with CRC recurrence and all-cause mortality using data from a prospective cohort study of 1719 stage I-III CRC patients in the Netherlands. Coffee consumption and other lifestyle characteristics were self-reported using questionnaires at the time of diagnosis. We retrieved recurrence and all-cause mortality data from the Netherlands Cancer Registry and the Personal Records Database, respectively. Cox proportional hazard regression models with and without restricted cubic splines were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) adjusted for age, sex, education, smoking status, cancer stage and tumor location. We observed 257 recurrences during a 6.2-year median follow-up and 309 deaths during a 6.6-year median follow-up. Consuming more than 4 cups/d of coffee compared to an intake of <2 cups/d was associated with a 32% lower risk of CRC recurrence (95% CI: 0.49, 0.94,). The association between coffee consumption and all-cause mortality was U-shaped; coffee intake seemed optimal at 3-5 cups/d with the lowest risk at 4 cups/d (HR: 0.68, 95% CI: 0.53, 0.88). Our results suggest that coffee consumption may be associated with a lower risk of CRC recurrence and all-cause mortality. The association between coffee consumption and all-cause mortality appeared nonlinear. More studies are needed to understand the mechanism by which coffee consumption might improve CRC prognosis.
Published: 2024

2. Pan-cancer analysis of pre-diagnostic blood metabolite concentrations in the European Prospective Investigation into Cancer and Nutrition.

Author: Breeur, M, Ferrari, P, Dossus, L, Jenab, M, Johansson, M, Rinaldi, S, Travis, RC, His, M, Key, TJ, Schmidt, JA, Overvad, K, Tjønneland, A, Kyrø, C, Rothwell, JA, Laouali, N, Severi, G, Kaaks, R, Katzke, V, Schulze, MB, Eichelmann, F, Palli, D, Grioni, S, Panico, S, Tumino, R, Sacerdote, C, Bueno-de-Mesquita, B, Olsen, KS, Sandanger, TM, Nøst, TH, Quirós, JR, Bonet, C, Barranco, MR, Chirlaque, M-D, Ardanaz, E, Sandsveden, M, Manjer, J, Vidman, L, Rentoft, M, Muller, D, Tsilidis, K, Heath, AK, Keun, H, Adamski, J, Keski-Rahkonen, P, Scalbert, A, Gunter, MJ, Viallon, V, Breeur, M, Ferrari, P, Dossus, L, Jenab, M, Johansson, M, Rinaldi, S, Travis, RC, His, M, Key, TJ, Schmidt, JA, Overvad, K, Tjønneland, A, Kyrø, C, Rothwell, JA, Laouali, N, Severi, G, Kaaks, R, Katzke, V, Schulze, MB, Eichelmann, F, Palli, D, Grioni, S, Panico, S, Tumino, R, Sacerdote, C, Bueno-de-Mesquita, B, Olsen, KS, Sandanger, TM, Nøst, TH, Quirós, JR, Bonet, C, Barranco, MR, Chirlaque, M-D, Ardanaz, E, Sandsveden, M, Manjer, J, Vidman, L, Rentoft, M, Muller, D, Tsilidis, K, Heath, AK, Keun, H, Adamski, J, Keski-Rahkonen, P, Scalbert, A, Gunter, MJ, and Viallon, V
Abstract: BACKGROUND: Epidemiological studies of associations between metabolites and cancer risk have typically focused on specific cancer types separately. Here, we designed a multivariate pan-cancer analysis to identify metabolites potentially associated with multiple cancer types, while also allowing the investigation of cancer type-specific associations. METHODS: We analysed targeted metabolomics data available for 5828 matched case-control pairs from cancer-specific case-control studies on breast, colorectal, endometrial, gallbladder, kidney, localized and advanced prostate cancer, and hepatocellular carcinoma nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. From pre-diagnostic blood levels of an initial set of 117 metabolites, 33 cluster representatives of strongly correlated metabolites and 17 single metabolites were derived by hierarchical clustering. The mutually adjusted associations of the resulting 50 metabolites with cancer risk were examined in penalized conditional logistic regression models adjusted for body mass index, using the data-shared lasso penalty. RESULTS: Out of the 50 studied metabolites, (i) six were inversely associated with the risk of most cancer types: glutamine, butyrylcarnitine, lysophosphatidylcholine a C18:2, and three clusters of phosphatidylcholines (PCs); (ii) three were positively associated with most cancer types: proline, decanoylcarnitine, and one cluster of PCs; and (iii) 10 were specifically associated with particular cancer types, including histidine that was inversely associated with colorectal cancer risk and one cluster of sphingomyelins that was inversely associated with risk of hepatocellular carcinoma and positively with endometrial cancer risk. CONCLUSIONS: These results could provide novel insights for the identification of pathways for cancer development, in particular those shared across different cancer types.
Published: 2022

3. A New Pipeline for the Normalization and Pooling of Metabolomics Data

Author: Viallon, V., His, M., Rinaldi, S., Breeur, M., Gicquiau, A., Hemon, B., Overvad, K., Tjønneland, A., Rostgaard-Hansen, A.L., Rothwell, J.A., Lecuyer, L., Severi, G., Kaaks, R., Johnson, T., Schulze, M.B., Palli, D., Agnoli, C., Panico, S., Tumino, R., Ricceri, F., Monique Verschuren, W.M., Engelfriet, P., Onland-Moret, C., Vermeulen, R., Nøst, T.H., Urbarova, I., Zamora-Ros, R., Rodriguez-Barranco, M., Amiano, P., Huerta, J.M., Ardanaz, E., Melander, O., Ottoson, F., Vidman, L., Rentoft, M., Schmidt, J.A., Travis, R.C., Weiderpass, E., Johansson, M., Dossus, L., Jenab, M., Gunter, M.J., Bermejo, J.L., Scherer, D., Salek, R.M., Keski-Rahkonen, P., Ferrari, P., Viallon, V., His, M., Rinaldi, S., Breeur, M., Gicquiau, A., Hemon, B., Overvad, K., Tjønneland, A., Rostgaard-Hansen, A.L., Rothwell, J.A., Lecuyer, L., Severi, G., Kaaks, R., Johnson, T., Schulze, M.B., Palli, D., Agnoli, C., Panico, S., Tumino, R., Ricceri, F., Monique Verschuren, W.M., Engelfriet, P., Onland-Moret, C., Vermeulen, R., Nøst, T.H., Urbarova, I., Zamora-Ros, R., Rodriguez-Barranco, M., Amiano, P., Huerta, J.M., Ardanaz, E., Melander, O., Ottoson, F., Vidman, L., Rentoft, M., Schmidt, J.A., Travis, R.C., Weiderpass, E., Johansson, M., Dossus, L., Jenab, M., Gunter, M.J., Bermejo, J.L., Scherer, D., Salek, R.M., Keski-Rahkonen, P., and Ferrari, P.
Abstract: Pooling metabolomics data across studies is often desirable to increase the statistical power of the analysis. However, this can raise methodological challenges as several preanalytical and analytical factors could introduce differences in measured concentrations and variability between datasets. Specifically, different studies may use variable sample types (e.g., serum versus plasma) collected, treated, and stored according to different protocols, and assayed in different laboratories using different instruments. To address these issues, a new pipeline was developed to normalize and pool metabolomics data through a set of sequential steps: (i) exclusions of the least informative observations and metabolites and removal of outliers; imputation of missing data; (ii) identification of the main sources of variability through principal component partial R-square (PC-PR2) analysis; (iii) application of linear mixed models to remove unwanted variability, including samples’ originating study and batch, and preserve biological variations while accounting for potential differences in the residual variances across studies. This pipeline was applied to targeted metabolomics data acquired using Biocrates AbsoluteIDQ kits in eight case-control studies nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Comprehensive examination of metabolomics measurements indicated that the pipeline improved the comparability of data across the studies. Our pipeline can be adapted to normalize other molecular data, including biomarkers as well as proteomics data, and could be used for pooling molecular datasets, for example in international consortia, to limit biases introduced by inter-study variability. This versatility of the pipeline makes our work of potential interest to molecular epidemiologists.
Published: 2021

4. Prospective identification of elevated circulating CDCP1 in patients years before onset of lung cancer

Author: Dagnino, S., Bodinier, B., Guida, F., Smith-Byrne, K., Petrovic, D., Whitaker, M.D., Nøst, T.H., Agnoli, C., Palli, D., Sacerdote, C., Panico, S., Tumino, R., Schulze, M.B., Johansson, M., Keski-Rahkonen, P., Scalbert, A., Vineis, P., Sandanger, T.M., Vermeulen, R.C.H., Chadeau-Hyam, M., Dagnino, S., Bodinier, B., Guida, F., Smith-Byrne, K., Petrovic, D., Whitaker, M.D., Nøst, T.H., Agnoli, C., Palli, D., Sacerdote, C., Panico, S., Tumino, R., Schulze, M.B., Johansson, M., Keski-Rahkonen, P., Scalbert, A., Vineis, P., Sandanger, T.M., Vermeulen, R.C.H., and Chadeau-Hyam, M.
Abstract: Increasing evidence points to a role for inflammation in lung carcinogenesis. A small number of circulating inflammatory proteins have been identified as showing elevated levels prior to lung cancer diagnosis, indicating the potential for prospective circulating protein concentration as a marker of early carcinogenesis. To identify novel markers of lung cancer risk, we measured a panel of 92 circulating inflammatory proteins in 648 prediagnostic blood samples from two prospective cohorts in Italy and Norway (women only). To preserve the comparability of results and protect against confounding factors, the main statistical analyses were conducted in women from both studies, with replication sought in men (Italian participants). Univariate and penalized regression models revealed for the first time higher blood levels of CDCP1 protein in cases that went on to develop lung cancer compared with controls, irrespective of time to diagnosis, smoking habits, and gender. This association was validated in an additional 450 samples. Associations were stronger for future cases of adenocarcinoma where CDCP1 showed better explanatory performance. Integrative analyses combining gene expression and protein levels of CDCP1 measured in the same individuals suggested a link between CDCP1 and the expression of transcripts of LRRN3 and SEM1. Enrichment analyses indicated a potential role for CDCP1 in pathways related to cell adhesion and mobility, such as the WNT/b-catenin pathway. Overall, this study identifies lung cancer-related dysregulation of CDCP1 expression years before diagnosis.
Published: 2021

5. Diet quality indices and dietary patterns are associated with plasma metabolites in colorectal cancer patients

Author: Geijsen, A, Kok, D.E., Zutphen, M. van, Keski-Rahkonen, P., Achaintre, D., Gicquiau, A., Gsur, A., Kruyt, F.M., Ulrich, C.M., Weijenberg, M.P., Wilt, J.H.W. de, Wesselink, E., Scalbert, A., Kampman, E., Duijnhoven, F. J. B. van, Geijsen, A, Kok, D.E., Zutphen, M. van, Keski-Rahkonen, P., Achaintre, D., Gicquiau, A., Gsur, A., Kruyt, F.M., Ulrich, C.M., Weijenberg, M.P., Wilt, J.H.W. de, Wesselink, E., Scalbert, A., Kampman, E., and Duijnhoven, F. J. B. van
Abstract: Contains fulltext : 238999.pdf (Publisher’s version ) (Open Access), PURPOSE: Emerging evidence suggests that diet is linked to survival in colorectal cancer patients, although underlying mechanisms are not fully understood. The aim of this study was to evaluate whether dietary exposures are associated with metabolite concentrations in colorectal cancer patients. METHODS: Concentrations of 134 metabolites of the Biocrates Absolute(IDQ) p180 kit were quantified in plasma samples collected at diagnosis from 195 stage I-IV colorectal cancer patients. Food frequency questionnaires were used to calculate adherence to the World Cancer Research Fund (WCRF) dietary recommendations and the Dutch Healthy Diet (DHD15) index as well as to construct dietary patterns using Principal Component Analysis. Multivariable linear regression models were used to determine associations between dietary exposures and metabolite concentrations. All models were adjusted for age, sex, body mass index, smoking status, analytical batch, cancer stage, and multiple testing using false discovery rate. RESULTS: Participants had a mean (SD) age of 66 (9) years, were mostly men (60%), and mostly diagnosed with stage II and III cancer. For the dietary pattern analyses, Western, Carnivore, and Prudent patterns were identified. Better adherence to the WCRF dietary recommendations was associated with lower concentrations of ten phosphatidylcholines. Higher intake of the Carnivore pattern was associated with higher concentrations of two phosphatidylcholines. The DHD15-index, Western pattern, or Prudent pattern were not associated with metabolite concentrations. CONCLUSION: In the current study, the WCRF dietary score and the Carnivore pattern are associated with phosphatidylcholines. Future research should elucidate the potential relevance of phosphatidylcholine metabolism in the colorectal cancer continuum. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov Identifier: NCT03191110.
Published: 2021

6. Metabolic perturbations prior to hepatocellular carcinoma diagnosis: Findings from a prospective observational cohort study

Author: IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Stepien, M., Keski-Rahkonen, P., Kiss, A., Robinot, N., Duarte-Salles, T., Murphy, N., Perlemuter, G., Viallon, V., Tjønneland, A., Rostgaard-Hansen, A.L., Dahm, C.C., Overvad, K., Boutron-Ruault, M.-C., Mancini, F.R., Mahamat-Saleh, Y., Aleksandrova, K., Kaaks, R., Kühn, T., Trichopoulou, A., Karakatsani, A., Panico, S., Tumino, R., Palli, D., Tagliabue, G., Naccarati, A., Vermeulen, R.C.H., Bueno-de-Mesquita, H.B., Weiderpass, E., Skeie, G., Ramón Quirós, J., Ardanaz, E., Mokoroa, O., Sala, N., Sánchez, M.-J., Huerta, J.M., Winkvist, A., Harlid, S., Ohlsson, B., Sjöberg, K., Wareham, N., Khaw, K.-T., Ferrari, P., Rothwell, J.A., Gunter, M., Riboli, E., Scalbert, A., Jenab, M., IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Stepien, M., Keski-Rahkonen, P., Kiss, A., Robinot, N., Duarte-Salles, T., Murphy, N., Perlemuter, G., Viallon, V., Tjønneland, A., Rostgaard-Hansen, A.L., Dahm, C.C., Overvad, K., Boutron-Ruault, M.-C., Mancini, F.R., Mahamat-Saleh, Y., Aleksandrova, K., Kaaks, R., Kühn, T., Trichopoulou, A., Karakatsani, A., Panico, S., Tumino, R., Palli, D., Tagliabue, G., Naccarati, A., Vermeulen, R.C.H., Bueno-de-Mesquita, H.B., Weiderpass, E., Skeie, G., Ramón Quirós, J., Ardanaz, E., Mokoroa, O., Sala, N., Sánchez, M.-J., Huerta, J.M., Winkvist, A., Harlid, S., Ohlsson, B., Sjöberg, K., Wareham, N., Khaw, K.-T., Ferrari, P., Rothwell, J.A., Gunter, M., Riboli, E., Scalbert, A., and Jenab, M.
Published: 2021

7. A New Pipeline for the Normalization and Pooling of Metabolomics Data

Author: IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Sub Inorganic Chemistry and Catalysis, Viallon, V., His, M., Rinaldi, S., Breeur, M., Gicquiau, A., Hemon, B., Overvad, K., Tjønneland, A., Rostgaard-Hansen, A.L., Rothwell, J.A., Lecuyer, L., Severi, G., Kaaks, R., Johnson, T., Schulze, M.B., Palli, D., Agnoli, C., Panico, S., Tumino, R., Ricceri, F., Monique Verschuren, W.M., Engelfriet, P., Onland-Moret, C., Vermeulen, R., Nøst, T.H., Urbarova, I., Zamora-Ros, R., Rodriguez-Barranco, M., Amiano, P., Huerta, J.M., Ardanaz, E., Melander, O., Ottoson, F., Vidman, L., Rentoft, M., Schmidt, J.A., Travis, R.C., Weiderpass, E., Johansson, M., Dossus, L., Jenab, M., Gunter, M.J., Bermejo, J.L., Scherer, D., Salek, R.M., Keski-Rahkonen, P., Ferrari, P., IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Sub Inorganic Chemistry and Catalysis, Viallon, V., His, M., Rinaldi, S., Breeur, M., Gicquiau, A., Hemon, B., Overvad, K., Tjønneland, A., Rostgaard-Hansen, A.L., Rothwell, J.A., Lecuyer, L., Severi, G., Kaaks, R., Johnson, T., Schulze, M.B., Palli, D., Agnoli, C., Panico, S., Tumino, R., Ricceri, F., Monique Verschuren, W.M., Engelfriet, P., Onland-Moret, C., Vermeulen, R., Nøst, T.H., Urbarova, I., Zamora-Ros, R., Rodriguez-Barranco, M., Amiano, P., Huerta, J.M., Ardanaz, E., Melander, O., Ottoson, F., Vidman, L., Rentoft, M., Schmidt, J.A., Travis, R.C., Weiderpass, E., Johansson, M., Dossus, L., Jenab, M., Gunter, M.J., Bermejo, J.L., Scherer, D., Salek, R.M., Keski-Rahkonen, P., and Ferrari, P.
Published: 2021

8. Circulating tryptophan metabolites and risk of colon cancer: Results from case-control and prospective cohort studies

Author: Papadimitriou, N., Papadimitriou, N., Gunter, M.J., Murphy, N., Gicquiau, A., Achaintre, D., Brezina, S., Gumpenberger, T., Baierl, A., Ose, J., Geijsen, A.J.M.R., van Roekel, E.H., Gsur, A., Gigic, B., Habermann, N., Ulrich, C.M., Kampman, E., Weijenberg, M.P., Ueland, P.M., Kaaks, R., Katzke, V., Krogh, V., Bueno-de-Mesquita, B., Ardanaz, E., Travis, R.C., Schulze, M.B., Sanchez, M.J., Colorado-Yohar, S.M., Weiderpass, E., Scalbert, A., Keski-Rahkonen, P., Papadimitriou, N., Papadimitriou, N., Gunter, M.J., Murphy, N., Gicquiau, A., Achaintre, D., Brezina, S., Gumpenberger, T., Baierl, A., Ose, J., Geijsen, A.J.M.R., van Roekel, E.H., Gsur, A., Gigic, B., Habermann, N., Ulrich, C.M., Kampman, E., Weijenberg, M.P., Ueland, P.M., Kaaks, R., Katzke, V., Krogh, V., Bueno-de-Mesquita, B., Ardanaz, E., Travis, R.C., Schulze, M.B., Sanchez, M.J., Colorado-Yohar, S.M., Weiderpass, E., Scalbert, A., and Keski-Rahkonen, P.
Abstract: Dysregulation of tryptophan metabolism has been linked to colorectal tumorigenesis; however, epidemiological studies investigating tryptophan metabolites in relation to colorectal cancer risk are limited. We studied associations of plasma tryptophan, serotonin and kynurenine with colon cancer risk in two studies with cancer patients and controls, and in one prospective cohort: ColoCare Study (110 patients/153 controls), the Colorectal Cancer Study of Austria (CORSA; 46 patients/390 controls) and the European Prospective Investigation into Cancer and Nutrition (EPIC; 456 matched case-control pairs). Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for colon cancer risk. Tryptophan was inversely associated with colon cancer risk in ColoCare (OR per 1-SD = 0.44; 95% CI, 0.31-0.64) and EPIC (OR per 1-SD = 0.86; 95% CI, 0.74-0.99). Comparing detectable vs nondetectable levels, serotonin was positively associated with colon cancer in CORSA (OR = 6.39; 95% CI, 3.61-11.3) and EPIC (OR = 2.03; 95% CI, 1.20-3.40). Kynurenine was inversely associated with colon cancer in ColoCare (OR per 1-SD = 0.74; 95% CI, 0.55-0.98), positively associated in CORSA (OR per 1-SD = 1.79; 95% CI, 1.27-2.52), while no association was observed in EPIC. The kynurenine-to-tryptophan ratio was positively associated with colon cancer in ColoCare (OR per 1-SD = 1.38; 95% CI, 1.03-1.84) and CORSA (OR per 1-SD = 1.44; 95% CI, 1.06-1.96), but not in EPIC. These results suggest that higher plasma tryptophan may be associated with lower colon cancer risk, while increased serotonin may be associated with a higher risk of colon cancer. The kynurenine-to-tryptophan ratio may also reflect altered tryptophan catabolism during colon cancer development.
Published: 2021

9. A New Pipeline for the Normalization and Pooling of Metabolomics Data

Author: Viallon, V, His, M, Rinaldi, S, Breeur, M, Gicquiau, A, Hemon, B, Overvad, K, Tjonneland, A, Rostgaard-Hansen, AL, Rothwell, JA, Lecuyer, L, Severi, G, Kaaks, R, Johnson, T, Schulze, MB, Palli, D, Agnoli, C, Panico, S, Tumino, R, Ricceri, F, Verschuren, WMM, Engelfriet, P, Onland-Moret, C, Vermeulen, R, Nost, TH, Urbarova, I, Zamora-Ros, R, Rodriguez-Barranco, M, Amiano, P, Huerta, JM, Ardanaz, E, Melander, O, Ottoson, F, Vidman, L, Rentoft, M, Schmidt, JA, Travis, RC, Weiderpass, E, Johansson, M, Dossus, L, Jenab, M, Gunter, MJ, Bermejo, JL, Scherer, D, Salek, RM, Keski-Rahkonen, P, Ferrari, P, Viallon, V, His, M, Rinaldi, S, Breeur, M, Gicquiau, A, Hemon, B, Overvad, K, Tjonneland, A, Rostgaard-Hansen, AL, Rothwell, JA, Lecuyer, L, Severi, G, Kaaks, R, Johnson, T, Schulze, MB, Palli, D, Agnoli, C, Panico, S, Tumino, R, Ricceri, F, Verschuren, WMM, Engelfriet, P, Onland-Moret, C, Vermeulen, R, Nost, TH, Urbarova, I, Zamora-Ros, R, Rodriguez-Barranco, M, Amiano, P, Huerta, JM, Ardanaz, E, Melander, O, Ottoson, F, Vidman, L, Rentoft, M, Schmidt, JA, Travis, RC, Weiderpass, E, Johansson, M, Dossus, L, Jenab, M, Gunter, MJ, Bermejo, JL, Scherer, D, Salek, RM, Keski-Rahkonen, P, and Ferrari, P
Abstract: Pooling metabolomics data across studies is often desirable to increase the statistical power of the analysis. However, this can raise methodological challenges as several preanalytical and analytical factors could introduce differences in measured concentrations and variability between datasets. Specifically, different studies may use variable sample types (e.g., serum versus plasma) collected, treated, and stored according to different protocols, and assayed in different laboratories using different instruments. To address these issues, a new pipeline was developed to normalize and pool metabolomics data through a set of sequential steps: (i) exclusions of the least informative observations and metabolites and removal of outliers; imputation of missing data; (ii) identification of the main sources of variability through principal component partial R-square (PC-PR2) analysis; (iii) application of linear mixed models to remove unwanted variability, including samples' originating study and batch, and preserve biological variations while accounting for potential differences in the residual variances across studies. This pipeline was applied to targeted metabolomics data acquired using Biocrates AbsoluteIDQ kits in eight case-control studies nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Comprehensive examination of metabolomics measurements indicated that the pipeline improved the comparability of data across the studies. Our pipeline can be adapted to normalize other molecular data, including biomarkers as well as proteomics data, and could be used for pooling molecular datasets, for example in international consortia, to limit biases introduced by inter-study variability. This versatility of the pipeline makes our work of potential interest to molecular epidemiologists.
Published: 2021

10. Diet quality indices and dietary patterns are associated with plasma metabolites in colorectal cancer patients

Author: Geijsen, A, Kok, D.E., Zutphen, M. van, Keski-Rahkonen, P., Achaintre, D., Gicquiau, A., Gsur, A., Kruyt, F.M., Ulrich, C.M., Weijenberg, M.P., Wilt, J.H.W. de, Wesselink, E., Scalbert, A., Kampman, E., Duijnhoven, F. J. B. van, Geijsen, A, Kok, D.E., Zutphen, M. van, Keski-Rahkonen, P., Achaintre, D., Gicquiau, A., Gsur, A., Kruyt, F.M., Ulrich, C.M., Weijenberg, M.P., Wilt, J.H.W. de, Wesselink, E., Scalbert, A., Kampman, E., and Duijnhoven, F. J. B. van
Abstract: Contains fulltext : 238999.pdf (Publisher’s version ) (Open Access), PURPOSE: Emerging evidence suggests that diet is linked to survival in colorectal cancer patients, although underlying mechanisms are not fully understood. The aim of this study was to evaluate whether dietary exposures are associated with metabolite concentrations in colorectal cancer patients. METHODS: Concentrations of 134 metabolites of the Biocrates Absolute(IDQ) p180 kit were quantified in plasma samples collected at diagnosis from 195 stage I-IV colorectal cancer patients. Food frequency questionnaires were used to calculate adherence to the World Cancer Research Fund (WCRF) dietary recommendations and the Dutch Healthy Diet (DHD15) index as well as to construct dietary patterns using Principal Component Analysis. Multivariable linear regression models were used to determine associations between dietary exposures and metabolite concentrations. All models were adjusted for age, sex, body mass index, smoking status, analytical batch, cancer stage, and multiple testing using false discovery rate. RESULTS: Participants had a mean (SD) age of 66 (9) years, were mostly men (60%), and mostly diagnosed with stage II and III cancer. For the dietary pattern analyses, Western, Carnivore, and Prudent patterns were identified. Better adherence to the WCRF dietary recommendations was associated with lower concentrations of ten phosphatidylcholines. Higher intake of the Carnivore pattern was associated with higher concentrations of two phosphatidylcholines. The DHD15-index, Western pattern, or Prudent pattern were not associated with metabolite concentrations. CONCLUSION: In the current study, the WCRF dietary score and the Carnivore pattern are associated with phosphatidylcholines. Future research should elucidate the potential relevance of phosphatidylcholine metabolism in the colorectal cancer continuum. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov Identifier: NCT03191110.
Published: 2021

11. Diet quality indices and dietary patterns are associated with plasma metabolites in colorectal cancer patients

Author: Geijsen, A, Kok, D.E., Zutphen, M. van, Keski-Rahkonen, P., Achaintre, D., Gicquiau, A., Gsur, A., Kruyt, F.M., Ulrich, C.M., Weijenberg, M.P., Wilt, J.H.W. de, Wesselink, E., Scalbert, A., Kampman, E., Duijnhoven, F. J. B. van, Geijsen, A, Kok, D.E., Zutphen, M. van, Keski-Rahkonen, P., Achaintre, D., Gicquiau, A., Gsur, A., Kruyt, F.M., Ulrich, C.M., Weijenberg, M.P., Wilt, J.H.W. de, Wesselink, E., Scalbert, A., Kampman, E., and Duijnhoven, F. J. B. van
Abstract: Contains fulltext : 238999.pdf (Publisher’s version ) (Open Access), PURPOSE: Emerging evidence suggests that diet is linked to survival in colorectal cancer patients, although underlying mechanisms are not fully understood. The aim of this study was to evaluate whether dietary exposures are associated with metabolite concentrations in colorectal cancer patients. METHODS: Concentrations of 134 metabolites of the Biocrates Absolute(IDQ) p180 kit were quantified in plasma samples collected at diagnosis from 195 stage I-IV colorectal cancer patients. Food frequency questionnaires were used to calculate adherence to the World Cancer Research Fund (WCRF) dietary recommendations and the Dutch Healthy Diet (DHD15) index as well as to construct dietary patterns using Principal Component Analysis. Multivariable linear regression models were used to determine associations between dietary exposures and metabolite concentrations. All models were adjusted for age, sex, body mass index, smoking status, analytical batch, cancer stage, and multiple testing using false discovery rate. RESULTS: Participants had a mean (SD) age of 66 (9) years, were mostly men (60%), and mostly diagnosed with stage II and III cancer. For the dietary pattern analyses, Western, Carnivore, and Prudent patterns were identified. Better adherence to the WCRF dietary recommendations was associated with lower concentrations of ten phosphatidylcholines. Higher intake of the Carnivore pattern was associated with higher concentrations of two phosphatidylcholines. The DHD15-index, Western pattern, or Prudent pattern were not associated with metabolite concentrations. CONCLUSION: In the current study, the WCRF dietary score and the Carnivore pattern are associated with phosphatidylcholines. Future research should elucidate the potential relevance of phosphatidylcholine metabolism in the colorectal cancer continuum. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov Identifier: NCT03191110.
Published: 2021

12. Metabolic perturbations prior to hepatocellular carcinoma diagnosis: Findings from a prospective observational cohort study

Author: IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Stepien, M., Keski-Rahkonen, P., Kiss, A., Robinot, N., Duarte-Salles, T., Murphy, N., Perlemuter, G., Viallon, V., Tjønneland, A., Rostgaard-Hansen, A.L., Dahm, C.C., Overvad, K., Boutron-Ruault, M.-C., Mancini, F.R., Mahamat-Saleh, Y., Aleksandrova, K., Kaaks, R., Kühn, T., Trichopoulou, A., Karakatsani, A., Panico, S., Tumino, R., Palli, D., Tagliabue, G., Naccarati, A., Vermeulen, R.C.H., Bueno-de-Mesquita, H.B., Weiderpass, E., Skeie, G., Ramón Quirós, J., Ardanaz, E., Mokoroa, O., Sala, N., Sánchez, M.-J., Huerta, J.M., Winkvist, A., Harlid, S., Ohlsson, B., Sjöberg, K., Wareham, N., Khaw, K.-T., Ferrari, P., Rothwell, J.A., Gunter, M., Riboli, E., Scalbert, A., Jenab, M., IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Stepien, M., Keski-Rahkonen, P., Kiss, A., Robinot, N., Duarte-Salles, T., Murphy, N., Perlemuter, G., Viallon, V., Tjønneland, A., Rostgaard-Hansen, A.L., Dahm, C.C., Overvad, K., Boutron-Ruault, M.-C., Mancini, F.R., Mahamat-Saleh, Y., Aleksandrova, K., Kaaks, R., Kühn, T., Trichopoulou, A., Karakatsani, A., Panico, S., Tumino, R., Palli, D., Tagliabue, G., Naccarati, A., Vermeulen, R.C.H., Bueno-de-Mesquita, H.B., Weiderpass, E., Skeie, G., Ramón Quirós, J., Ardanaz, E., Mokoroa, O., Sala, N., Sánchez, M.-J., Huerta, J.M., Winkvist, A., Harlid, S., Ohlsson, B., Sjöberg, K., Wareham, N., Khaw, K.-T., Ferrari, P., Rothwell, J.A., Gunter, M., Riboli, E., Scalbert, A., and Jenab, M.
Published: 2021

13. A New Pipeline for the Normalization and Pooling of Metabolomics Data

Author: IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Sub Inorganic Chemistry and Catalysis, Viallon, V., His, M., Rinaldi, S., Breeur, M., Gicquiau, A., Hemon, B., Overvad, K., Tjønneland, A., Rostgaard-Hansen, A.L., Rothwell, J.A., Lecuyer, L., Severi, G., Kaaks, R., Johnson, T., Schulze, M.B., Palli, D., Agnoli, C., Panico, S., Tumino, R., Ricceri, F., Monique Verschuren, W.M., Engelfriet, P., Onland-Moret, C., Vermeulen, R., Nøst, T.H., Urbarova, I., Zamora-Ros, R., Rodriguez-Barranco, M., Amiano, P., Huerta, J.M., Ardanaz, E., Melander, O., Ottoson, F., Vidman, L., Rentoft, M., Schmidt, J.A., Travis, R.C., Weiderpass, E., Johansson, M., Dossus, L., Jenab, M., Gunter, M.J., Bermejo, J.L., Scherer, D., Salek, R.M., Keski-Rahkonen, P., Ferrari, P., IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Sub Inorganic Chemistry and Catalysis, Viallon, V., His, M., Rinaldi, S., Breeur, M., Gicquiau, A., Hemon, B., Overvad, K., Tjønneland, A., Rostgaard-Hansen, A.L., Rothwell, J.A., Lecuyer, L., Severi, G., Kaaks, R., Johnson, T., Schulze, M.B., Palli, D., Agnoli, C., Panico, S., Tumino, R., Ricceri, F., Monique Verschuren, W.M., Engelfriet, P., Onland-Moret, C., Vermeulen, R., Nøst, T.H., Urbarova, I., Zamora-Ros, R., Rodriguez-Barranco, M., Amiano, P., Huerta, J.M., Ardanaz, E., Melander, O., Ottoson, F., Vidman, L., Rentoft, M., Schmidt, J.A., Travis, R.C., Weiderpass, E., Johansson, M., Dossus, L., Jenab, M., Gunter, M.J., Bermejo, J.L., Scherer, D., Salek, R.M., Keski-Rahkonen, P., and Ferrari, P.
Published: 2021

14. Metabolic perturbations prior to hepatocellular carcinoma diagnosis: Findings from a prospective observational cohort study

Author: IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Stepien, M., Keski-Rahkonen, P., Kiss, A., Robinot, N., Duarte-Salles, T., Murphy, N., Perlemuter, G., Viallon, V., Tjønneland, A., Rostgaard-Hansen, A.L., Dahm, C.C., Overvad, K., Boutron-Ruault, M.-C., Mancini, F.R., Mahamat-Saleh, Y., Aleksandrova, K., Kaaks, R., Kühn, T., Trichopoulou, A., Karakatsani, A., Panico, S., Tumino, R., Palli, D., Tagliabue, G., Naccarati, A., Vermeulen, R.C.H., Bueno-de-Mesquita, H.B., Weiderpass, E., Skeie, G., Ramón Quirós, J., Ardanaz, E., Mokoroa, O., Sala, N., Sánchez, M.-J., Huerta, J.M., Winkvist, A., Harlid, S., Ohlsson, B., Sjöberg, K., Wareham, N., Khaw, K.-T., Ferrari, P., Rothwell, J.A., Gunter, M., Riboli, E., Scalbert, A., Jenab, M., IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Stepien, M., Keski-Rahkonen, P., Kiss, A., Robinot, N., Duarte-Salles, T., Murphy, N., Perlemuter, G., Viallon, V., Tjønneland, A., Rostgaard-Hansen, A.L., Dahm, C.C., Overvad, K., Boutron-Ruault, M.-C., Mancini, F.R., Mahamat-Saleh, Y., Aleksandrova, K., Kaaks, R., Kühn, T., Trichopoulou, A., Karakatsani, A., Panico, S., Tumino, R., Palli, D., Tagliabue, G., Naccarati, A., Vermeulen, R.C.H., Bueno-de-Mesquita, H.B., Weiderpass, E., Skeie, G., Ramón Quirós, J., Ardanaz, E., Mokoroa, O., Sala, N., Sánchez, M.-J., Huerta, J.M., Winkvist, A., Harlid, S., Ohlsson, B., Sjöberg, K., Wareham, N., Khaw, K.-T., Ferrari, P., Rothwell, J.A., Gunter, M., Riboli, E., Scalbert, A., and Jenab, M.
Published: 2021

15. A New Pipeline for the Normalization and Pooling of Metabolomics Data

Author: IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Sub Inorganic Chemistry and Catalysis, Viallon, V., His, M., Rinaldi, S., Breeur, M., Gicquiau, A., Hemon, B., Overvad, K., Tjønneland, A., Rostgaard-Hansen, A.L., Rothwell, J.A., Lecuyer, L., Severi, G., Kaaks, R., Johnson, T., Schulze, M.B., Palli, D., Agnoli, C., Panico, S., Tumino, R., Ricceri, F., Monique Verschuren, W.M., Engelfriet, P., Onland-Moret, C., Vermeulen, R., Nøst, T.H., Urbarova, I., Zamora-Ros, R., Rodriguez-Barranco, M., Amiano, P., Huerta, J.M., Ardanaz, E., Melander, O., Ottoson, F., Vidman, L., Rentoft, M., Schmidt, J.A., Travis, R.C., Weiderpass, E., Johansson, M., Dossus, L., Jenab, M., Gunter, M.J., Bermejo, J.L., Scherer, D., Salek, R.M., Keski-Rahkonen, P., Ferrari, P., IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Sub Inorganic Chemistry and Catalysis, Viallon, V., His, M., Rinaldi, S., Breeur, M., Gicquiau, A., Hemon, B., Overvad, K., Tjønneland, A., Rostgaard-Hansen, A.L., Rothwell, J.A., Lecuyer, L., Severi, G., Kaaks, R., Johnson, T., Schulze, M.B., Palli, D., Agnoli, C., Panico, S., Tumino, R., Ricceri, F., Monique Verschuren, W.M., Engelfriet, P., Onland-Moret, C., Vermeulen, R., Nøst, T.H., Urbarova, I., Zamora-Ros, R., Rodriguez-Barranco, M., Amiano, P., Huerta, J.M., Ardanaz, E., Melander, O., Ottoson, F., Vidman, L., Rentoft, M., Schmidt, J.A., Travis, R.C., Weiderpass, E., Johansson, M., Dossus, L., Jenab, M., Gunter, M.J., Bermejo, J.L., Scherer, D., Salek, R.M., Keski-Rahkonen, P., and Ferrari, P.
Published: 2021

16. Circulating tryptophan metabolites and risk of colon cancer: Results from case-control and prospective cohort studies

Author: Papadimitriou, N., Gunter, M.J., Murphy, N., Gicquiau, A., Achaintre, D., Brezina, S., Gumpenberger, T., Baierl, A., Ose, J., Geijsen, A.J.M.R., van Roekel, E.H., Gsur, A., Gigic, B., Habermann, N., Ulrich, C.M., Kampman, E., Weijenberg, M.P., Ueland, P.M., Kaaks, R., Katzke, V., Krogh, V., Bueno-de-Mesquita, B., Ardanaz, E., Travis, R.C., Schulze, M.B., Sanchez, M.J., Colorado-Yohar, S.M., Weiderpass, E., Scalbert, A., Keski-Rahkonen, P., Papadimitriou, N., Gunter, M.J., Murphy, N., Gicquiau, A., Achaintre, D., Brezina, S., Gumpenberger, T., Baierl, A., Ose, J., Geijsen, A.J.M.R., van Roekel, E.H., Gsur, A., Gigic, B., Habermann, N., Ulrich, C.M., Kampman, E., Weijenberg, M.P., Ueland, P.M., Kaaks, R., Katzke, V., Krogh, V., Bueno-de-Mesquita, B., Ardanaz, E., Travis, R.C., Schulze, M.B., Sanchez, M.J., Colorado-Yohar, S.M., Weiderpass, E., Scalbert, A., and Keski-Rahkonen, P.
Abstract: Dysregulation of tryptophan metabolism has been linked to colorectal tumorigenesis; however, epidemiological studies investigating tryptophan metabolites in relation to colorectal cancer risk are limited. We studied associations of plasma tryptophan, serotonin and kynurenine with colon cancer risk in two studies with cancer patients and controls, and in one prospective cohort: ColoCare Study (110 patients/153 controls), the Colorectal Cancer Study of Austria (CORSA; 46 patients/390 controls) and the European Prospective Investigation into Cancer and Nutrition (EPIC; 456 matched case-control pairs). Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for colon cancer risk. Tryptophan was inversely associated with colon cancer risk in ColoCare (OR per 1-SD = 0.44; 95% CI, 0.31-0.64) and EPIC (OR per 1-SD = 0.86; 95% CI, 0.74-0.99). Comparing detectable vs nondetectable levels, serotonin was positively associated with colon cancer in CORSA (OR = 6.39; 95% CI, 3.61-11.3) and EPIC (OR = 2.03; 95% CI, 1.20-3.40). Kynurenine was inversely associated with colon cancer in ColoCare (OR per 1-SD = 0.74; 95% CI, 0.55-0.98), positively associated in CORSA (OR per 1-SD = 1.79; 95% CI, 1.27-2.52), while no association was observed in EPIC. The kynurenine-to-tryptophan ratio was positively associated with colon cancer in ColoCare (OR per 1-SD = 1.38; 95% CI, 1.03-1.84) and CORSA (OR per 1-SD = 1.44; 95% CI, 1.06-1.96), but not in EPIC. These results suggest that higher plasma tryptophan may be associated with lower colon cancer risk, while increased serotonin may be associated with a higher risk of colon cancer. The kynurenine-to-tryptophan ratio may also reflect altered tryptophan catabolism during colon cancer development.
Published: 2021

17. A multi-omic analysis of birthweight in newborn cord blood reveals new underlying mechanisms related to cholesterol metabolism

Author: Alfano, R., Chadeau-Hyam, M., Ghantous, A., Keski-Rahkonen, P., Chatzi, L., Perez, A.E., Herceg, Z., Kogevinas, M., de Kok, T.M., Nawrot, T.S., Novoloaca, A., Patel, C.J., Pizzi, C., Robinot, N., Rusconi, F., Scalbert, A., Sunyer, J., Vermeulen, R., Vrijheid, M., Vineis, P., Robinson, O., Plusquin, M., Alfano, R., Chadeau-Hyam, M., Ghantous, A., Keski-Rahkonen, P., Chatzi, L., Perez, A.E., Herceg, Z., Kogevinas, M., de Kok, T.M., Nawrot, T.S., Novoloaca, A., Patel, C.J., Pizzi, C., Robinot, N., Rusconi, F., Scalbert, A., Sunyer, J., Vermeulen, R., Vrijheid, M., Vineis, P., Robinson, O., and Plusquin, M.
Abstract: Background Birthweight reflects in utero exposures and later health evolution. Despite existing studies employing high-dimensional molecular measurements, the understanding of underlying mechanisms of birthweight remains limited. Methods To investigate the systems biology of birthweight, we cross-sectionally integrated the methylome, the transcriptome, the metabolome and a set of inflammatory proteins measured in cord blood samples, collected from four birth-cohorts (n = 489). We focused on two sets of 68 metabolites and 903 CpGs previously related to birthweight and investigated the correlation structures existing between these two sets and all other omic features via bipartite Pearson correlations. Results This dataset revealed that the set of metabolome and methylome signatures of birthweight have seven signals in common, including three metabolites [PC(34:2), plasmalogen PC(36:4)/PC(O-36:5), and a compound with m/z of 781.0545], two CpGs (on the DHCR24 and SC4MOL gene), and two proteins (periostin and CCL22). CCL22, a macrophage-derived chemokine has not been previously identified in relation to birthweight. Since the results of the omics integration indicated the central role of cholesterol metabolism, we explored the association of cholesterol levels in cord blood with birthweight in the ENVIRONAGE cohort (n = 1097), finding that higher birthweight was associated with increased high-density lipoprotein cholesterol and that high-density lipoprotein cholesterol was lower in small versus large for gestational age newborns. Conclusions Our data suggests that an integration of different omic-layers in addition to single omics studies is a useful approach to generate new hypotheses regarding biological mechanisms. CCL22 and cholesterol metabolism in cord blood play a mechanistic role in birthweight.
Published: 2020

18. A metabolomic study of red and processed meat intake and acylcarnitine concentrations in human urine and blood

Author: Wedekind, R., Kiss, A., Keski-Rahkonen, P., Viallon, V., Rothwell, J.A., Cross, A.J., Rostgaard-Hansen, A.L., Sandanger, T.M., Jakszyn, P., Pala, V., Vermeulen, R., Schulze, M.B., Kühn, T., Johnson, T., Trichopoulou, A., Peppa, E., Vechia, C.L., Masala, G., Tumino, R., Sacerdote, C., Wittenbecher, C., de Magistris, M.S., Dahm, C.C., Severi, G., Mancini, F.R., Weiderpass, E., Gunter, M.J., Huybrechts, I., Scalbert, A., Wedekind, R., Kiss, A., Keski-Rahkonen, P., Viallon, V., Rothwell, J.A., Cross, A.J., Rostgaard-Hansen, A.L., Sandanger, T.M., Jakszyn, P., Pala, V., Vermeulen, R., Schulze, M.B., Kühn, T., Johnson, T., Trichopoulou, A., Peppa, E., Vechia, C.L., Masala, G., Tumino, R., Sacerdote, C., Wittenbecher, C., de Magistris, M.S., Dahm, C.C., Severi, G., Mancini, F.R., Weiderpass, E., Gunter, M.J., Huybrechts, I., and Scalbert, A.
Abstract: Background Acylcarnitines (ACs) play a major role in fatty acid metabolism and are potential markers of metabolic dysfunction with higher blood concentrations reported in obese and diabetic individuals. Diet, and in particular red and processed meat intake, has been shown to influence AC concentrations but data on the effect of meat consumption on AC concentrations is limited. Objectives To investigate the effect of red and processed meat intake on AC concentrations in plasma and urine using a randomized controlled trial with replication in an observational cohort. Methods In the randomized crossover trial, 12 volunteers successively consumed 2 different diets containing either pork or tofu for 3 d each. A panel of 44 ACs including several oxidized ACs was analyzed by LC-MS in plasma and urine samples collected after the 3-d period. ACs that were associated with pork intake were then measured in urine (n = 474) and serum samples (n = 451) from the European Prospective Investigation into Cancer and nutrition (EPIC) study and tested for associations with habitual red and processed meat intake derived from dietary questionnaires. Results In urine samples from the intervention study, pork intake was positively associated with concentrations of 18 short- and medium-chain ACs. Eleven of these were also positively associated with habitual red and processed meat intake in the EPIC cross-sectional study. In blood, C18:0 was positively associated with red meat intake in both the intervention study (q = 0.004, Student's t-test) and the cross-sectional study (q = 0.033, linear regression). Conclusions AC concentrations in urine and blood were associated with red meat intake in both a highly controlled intervention study and in subjects of a cross-sectional study. Our data on the role of meat intake on this important pathway of fatty acid and energy metabolism may help understanding the role of red meat consumption in the e
Published: 2020

19. Prenatal Exposure to Multiple Air Pollutants, Mediating Molecular Mechanisms, and Shifts in Birthweight

Author: Laine, J.E., Bodinier, B., Robinson, O., Plusquin, M., Scalbert, A., Keski-Rahkonen, P., Robinot, N., Vermeulen, R., Pizzi, C., Asta, F., Nawrot, T., Gulliver, J., Chatzi, L., Kogevinas, M., Nieuwenhuijsen, M., Sunyer, J., Vrijheid, M., Chadeau-Hyam, M., Vineis, P., Laine, J.E., Bodinier, B., Robinson, O., Plusquin, M., Scalbert, A., Keski-Rahkonen, P., Robinot, N., Vermeulen, R., Pizzi, C., Asta, F., Nawrot, T., Gulliver, J., Chatzi, L., Kogevinas, M., Nieuwenhuijsen, M., Sunyer, J., Vrijheid, M., Chadeau-Hyam, M., and Vineis, P.
Abstract: Mechanisms underlying adverse birth and later in life health effects from exposure to air pollution during the prenatal period have not been not fully elucidated, especially in the context of mixtures. We assessed the effects of prenatal exposure to mixtures of air pollutants of particulate matter (PM), PM2.5, PM10, nitrogen oxides, NO2, NOx, ultrafine particles (UFP), and oxidative potential (OP) of PM2.5 on infant birthweight in four European birth cohorts and the mechanistic underpinnings through cross-omics of metabolites and inflammatory proteins. The association between mixtures of air pollutants and birthweight z-scores (standardized for gestational age) was assessed for three different mixture models, using Bayesian machine kernel regression (BKMR). We determined the direct effect for PM2.5, PM10, NO2, and mediation by cross-omic signatures (identified using sparse partial least-squares regression) using causal mediation BKMR models. There was a negative association with birthweight z-scores and exposure to mixtures of air pollutants, where up to −0.21 or approximately a 96 g decrease in birthweight, comparing the 75th percentile to the median level of exposure to the air pollutant mixture could occur. Shifts in birthweight z-scores from prenatal exposure to PM2.5, PM10, and NO2 were mediated by molecular mechanisms, represented by cross-omics scores. Interleukin-17 and epidermal growth factor were identified as important inflammatory responses underlyingair pollution-associated shifts in birthweight. Our results signify that by identifying mechanisms through which mixtures of air pollutants operate, the causality of air pollution-associated shifts in birthweight is better supported, substantiating the need for reducing exposure in vulnerable populations.
Published: 2020

20. Plasma metabolites associated with colorectal cancer stage: Findings from an international consortium

Author: Geijsen, A., Roekel, E.H. van, Duijnhoven, F. J. B. van, Achaintre, D., Bachleitner-Hofmann, T., Baierl, A., Bergmann, M.M., Boehm, J., Bours, M.J., Brenner, H., Breukink, S.O., Brezina, S., Chang-Claude, J., Herpel, E., Wilt, J.H.W. de, Gicquiau, A., Gigic, B., Gumpenberger, T., Hansson, B.M.E., Hoffmeister, M., Holowatyj, A.N., Karner-Hanusch, J., Keski-Rahkonen, P., Keulen, E.T.P., Koole, J.L., Leeb, G., Ose, J., Schirmacher, P., Schneider, Markus, Schrotz-King, P., Stift, A., Ulvik, A., Vogelaar, F.J., Wesselink, E., Zutphen, M. van, Gsur, A., Habermann, N., Kampman, E., Scalbert, A., Ueland, P.M., Ulrich, A.B., Ulrich, C.M., Weijenberg, M.P., Kok, D.E., Geijsen, A., Roekel, E.H. van, Duijnhoven, F. J. B. van, Achaintre, D., Bachleitner-Hofmann, T., Baierl, A., Bergmann, M.M., Boehm, J., Bours, M.J., Brenner, H., Breukink, S.O., Brezina, S., Chang-Claude, J., Herpel, E., Wilt, J.H.W. de, Gicquiau, A., Gigic, B., Gumpenberger, T., Hansson, B.M.E., Hoffmeister, M., Holowatyj, A.N., Karner-Hanusch, J., Keski-Rahkonen, P., Keulen, E.T.P., Koole, J.L., Leeb, G., Ose, J., Schirmacher, P., Schneider, Markus, Schrotz-King, P., Stift, A., Ulvik, A., Vogelaar, F.J., Wesselink, E., Zutphen, M. van, Gsur, A., Habermann, N., Kampman, E., Scalbert, A., Ueland, P.M., Ulrich, A.B., Ulrich, C.M., Weijenberg, M.P., and Kok, D.E.
Abstract: Contains fulltext : 220955.pdf (Publisher’s version ) (Open Access), Colorectal cancer is the second most common cause of cancer-related death globally, with marked differences in prognosis by disease stage at diagnosis. We studied circulating metabolites in relation to disease stage to improve the understanding of metabolic pathways related to colorectal cancer progression. We investigated plasma concentrations of 130 metabolites among 744 Stages I-IV colorectal cancer patients from ongoing cohort studies. Plasma samples, collected at diagnosis, were analyzed with liquid chromatography-mass spectrometry using the Biocrates AbsoluteIDQ™ p180 kit. We assessed associations between metabolite concentrations and stage using multinomial and multivariable logistic regression models. Analyses were adjusted for potential confounders as well as multiple testing using false discovery rate (FDR) correction. Patients presented with 23, 28, 39 and 10% of Stages I-IV disease, respectively. Concentrations of sphingomyelin C26:0 were lower in Stage III patients compared to Stage I patients (p(FDR) < 0.05). Concentrations of sphingomyelin C18:0 and phosphatidylcholine (diacyl) C32:0 were statistically significantly higher, while citrulline, histidine, phosphatidylcholine (diacyl) C34:4, phosphatidylcholine (acyl-alkyl) C40:1 and lysophosphatidylcholines (acyl) C16:0 and C17:0 concentrations were lower in Stage IV compared to Stage I patients (p(FDR) < 0.05). Our results suggest that metabolic pathways involving among others citrulline and histidine, implicated previously in colorectal cancer development, may also be linked to colorectal cancer progression.
Published: 2020

21. Prenatal Exposure to Multiple Air Pollutants, Mediating Molecular Mechanisms, and Shifts in Birthweight

Author: IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Laine, J.E., Bodinier, B., Robinson, O., Plusquin, M., Scalbert, A., Keski-Rahkonen, P., Robinot, N., Vermeulen, R., Pizzi, C., Asta, F., Nawrot, T., Gulliver, J., Chatzi, L., Kogevinas, M., Nieuwenhuijsen, M., Sunyer, J., Vrijheid, M., Chadeau-Hyam, M., Vineis, P., IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Laine, J.E., Bodinier, B., Robinson, O., Plusquin, M., Scalbert, A., Keski-Rahkonen, P., Robinot, N., Vermeulen, R., Pizzi, C., Asta, F., Nawrot, T., Gulliver, J., Chatzi, L., Kogevinas, M., Nieuwenhuijsen, M., Sunyer, J., Vrijheid, M., Chadeau-Hyam, M., and Vineis, P.
Published: 2020

22. A metabolomic study of red and processed meat intake and acylcarnitine concentrations in human urine and blood

Author: IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Wedekind, R., Kiss, A., Keski-Rahkonen, P., Viallon, V., Rothwell, J.A., Cross, A.J., Rostgaard-Hansen, A.L., Sandanger, T.M., Jakszyn, P., Pala, V., Vermeulen, R., Schulze, M.B., Kühn, T., Johnson, T., Trichopoulou, A., Peppa, E., Vechia, C.L., Masala, G., Tumino, R., Sacerdote, C., Wittenbecher, C., de Magistris, M.S., Dahm, C.C., Severi, G., Mancini, F.R., Weiderpass, E., Gunter, M.J., Huybrechts, I., Scalbert, A., IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Wedekind, R., Kiss, A., Keski-Rahkonen, P., Viallon, V., Rothwell, J.A., Cross, A.J., Rostgaard-Hansen, A.L., Sandanger, T.M., Jakszyn, P., Pala, V., Vermeulen, R., Schulze, M.B., Kühn, T., Johnson, T., Trichopoulou, A., Peppa, E., Vechia, C.L., Masala, G., Tumino, R., Sacerdote, C., Wittenbecher, C., de Magistris, M.S., Dahm, C.C., Severi, G., Mancini, F.R., Weiderpass, E., Gunter, M.J., Huybrechts, I., and Scalbert, A.
Published: 2020

23. A multi-omic analysis of birthweight in newborn cord blood reveals new underlying mechanisms related to cholesterol metabolism

Author: IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Alfano, R., Chadeau-Hyam, M., Ghantous, A., Keski-Rahkonen, P., Chatzi, L., Perez, A.E., Herceg, Z., Kogevinas, M., de Kok, T.M., Nawrot, T.S., Novoloaca, A., Patel, C.J., Pizzi, C., Robinot, N., Rusconi, F., Scalbert, A., Sunyer, J., Vermeulen, R., Vrijheid, M., Vineis, P., Robinson, O., Plusquin, M., IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Alfano, R., Chadeau-Hyam, M., Ghantous, A., Keski-Rahkonen, P., Chatzi, L., Perez, A.E., Herceg, Z., Kogevinas, M., de Kok, T.M., Nawrot, T.S., Novoloaca, A., Patel, C.J., Pizzi, C., Robinot, N., Rusconi, F., Scalbert, A., Sunyer, J., Vermeulen, R., Vrijheid, M., Vineis, P., Robinson, O., and Plusquin, M.
Published: 2020

24. Plasma metabolites associated with colorectal cancer stage: Findings from an international consortium

Author: Geijsen, A., Roekel, E.H. van, Duijnhoven, F. J. B. van, Achaintre, D., Bachleitner-Hofmann, T., Baierl, A., Bergmann, M.M., Boehm, J., Bours, M.J., Brenner, H., Breukink, S.O., Brezina, S., Chang-Claude, J., Herpel, E., Wilt, J.H.W. de, Gicquiau, A., Gigic, B., Gumpenberger, T., Hansson, B.M.E., Hoffmeister, M., Holowatyj, A.N., Karner-Hanusch, J., Keski-Rahkonen, P., Keulen, E.T.P., Koole, J.L., Leeb, G., Ose, J., Schirmacher, P., Schneider, Markus, Schrotz-King, P., Stift, A., Ulvik, A., Vogelaar, F.J., Wesselink, E., Zutphen, M. van, Gsur, A., Habermann, N., Kampman, E., Scalbert, A., Ueland, P.M., Ulrich, A.B., Ulrich, C.M., Weijenberg, M.P., Kok, D.E., Geijsen, A., Roekel, E.H. van, Duijnhoven, F. J. B. van, Achaintre, D., Bachleitner-Hofmann, T., Baierl, A., Bergmann, M.M., Boehm, J., Bours, M.J., Brenner, H., Breukink, S.O., Brezina, S., Chang-Claude, J., Herpel, E., Wilt, J.H.W. de, Gicquiau, A., Gigic, B., Gumpenberger, T., Hansson, B.M.E., Hoffmeister, M., Holowatyj, A.N., Karner-Hanusch, J., Keski-Rahkonen, P., Keulen, E.T.P., Koole, J.L., Leeb, G., Ose, J., Schirmacher, P., Schneider, Markus, Schrotz-King, P., Stift, A., Ulvik, A., Vogelaar, F.J., Wesselink, E., Zutphen, M. van, Gsur, A., Habermann, N., Kampman, E., Scalbert, A., Ueland, P.M., Ulrich, A.B., Ulrich, C.M., Weijenberg, M.P., and Kok, D.E.
Abstract: Contains fulltext : 220955.pdf (Publisher’s version ) (Open Access), Colorectal cancer is the second most common cause of cancer-related death globally, with marked differences in prognosis by disease stage at diagnosis. We studied circulating metabolites in relation to disease stage to improve the understanding of metabolic pathways related to colorectal cancer progression. We investigated plasma concentrations of 130 metabolites among 744 Stages I-IV colorectal cancer patients from ongoing cohort studies. Plasma samples, collected at diagnosis, were analyzed with liquid chromatography-mass spectrometry using the Biocrates AbsoluteIDQ™ p180 kit. We assessed associations between metabolite concentrations and stage using multinomial and multivariable logistic regression models. Analyses were adjusted for potential confounders as well as multiple testing using false discovery rate (FDR) correction. Patients presented with 23, 28, 39 and 10% of Stages I-IV disease, respectively. Concentrations of sphingomyelin C26:0 were lower in Stage III patients compared to Stage I patients (p(FDR) < 0.05). Concentrations of sphingomyelin C18:0 and phosphatidylcholine (diacyl) C32:0 were statistically significantly higher, while citrulline, histidine, phosphatidylcholine (diacyl) C34:4, phosphatidylcholine (acyl-alkyl) C40:1 and lysophosphatidylcholines (acyl) C16:0 and C17:0 concentrations were lower in Stage IV compared to Stage I patients (p(FDR) < 0.05). Our results suggest that metabolic pathways involving among others citrulline and histidine, implicated previously in colorectal cancer development, may also be linked to colorectal cancer progression.
Published: 2020

25. Plasma metabolites associated with colorectal cancer stage: Findings from an international consortium

Author: Geijsen, A., Roekel, E.H. van, Duijnhoven, F. J. B. van, Achaintre, D., Bachleitner-Hofmann, T., Baierl, A., Bergmann, M.M., Boehm, J., Bours, M.J., Brenner, H., Breukink, S.O., Brezina, S., Chang-Claude, J., Herpel, E., Wilt, J.H.W. de, Gicquiau, A., Gigic, B., Gumpenberger, T., Hansson, B.M.E., Hoffmeister, M., Holowatyj, A.N., Karner-Hanusch, J., Keski-Rahkonen, P., Keulen, E.T.P., Koole, J.L., Leeb, G., Ose, J., Schirmacher, P., Schneider, Markus, Schrotz-King, P., Stift, A., Ulvik, A., Vogelaar, F.J., Wesselink, E., Zutphen, M. van, Gsur, A., Habermann, N., Kampman, E., Scalbert, A., Ueland, P.M., Ulrich, A.B., Ulrich, C.M., Weijenberg, M.P., Kok, D.E., Geijsen, A., Roekel, E.H. van, Duijnhoven, F. J. B. van, Achaintre, D., Bachleitner-Hofmann, T., Baierl, A., Bergmann, M.M., Boehm, J., Bours, M.J., Brenner, H., Breukink, S.O., Brezina, S., Chang-Claude, J., Herpel, E., Wilt, J.H.W. de, Gicquiau, A., Gigic, B., Gumpenberger, T., Hansson, B.M.E., Hoffmeister, M., Holowatyj, A.N., Karner-Hanusch, J., Keski-Rahkonen, P., Keulen, E.T.P., Koole, J.L., Leeb, G., Ose, J., Schirmacher, P., Schneider, Markus, Schrotz-King, P., Stift, A., Ulvik, A., Vogelaar, F.J., Wesselink, E., Zutphen, M. van, Gsur, A., Habermann, N., Kampman, E., Scalbert, A., Ueland, P.M., Ulrich, A.B., Ulrich, C.M., Weijenberg, M.P., and Kok, D.E.
Abstract: Contains fulltext : 220955.pdf (Publisher’s version ) (Open Access), Colorectal cancer is the second most common cause of cancer-related death globally, with marked differences in prognosis by disease stage at diagnosis. We studied circulating metabolites in relation to disease stage to improve the understanding of metabolic pathways related to colorectal cancer progression. We investigated plasma concentrations of 130 metabolites among 744 Stages I-IV colorectal cancer patients from ongoing cohort studies. Plasma samples, collected at diagnosis, were analyzed with liquid chromatography-mass spectrometry using the Biocrates AbsoluteIDQ™ p180 kit. We assessed associations between metabolite concentrations and stage using multinomial and multivariable logistic regression models. Analyses were adjusted for potential confounders as well as multiple testing using false discovery rate (FDR) correction. Patients presented with 23, 28, 39 and 10% of Stages I-IV disease, respectively. Concentrations of sphingomyelin C26:0 were lower in Stage III patients compared to Stage I patients (p(FDR) < 0.05). Concentrations of sphingomyelin C18:0 and phosphatidylcholine (diacyl) C32:0 were statistically significantly higher, while citrulline, histidine, phosphatidylcholine (diacyl) C34:4, phosphatidylcholine (acyl-alkyl) C40:1 and lysophosphatidylcholines (acyl) C16:0 and C17:0 concentrations were lower in Stage IV compared to Stage I patients (p(FDR) < 0.05). Our results suggest that metabolic pathways involving among others citrulline and histidine, implicated previously in colorectal cancer development, may also be linked to colorectal cancer progression.
Published: 2020

26. Prenatal Exposure to Multiple Air Pollutants, Mediating Molecular Mechanisms, and Shifts in Birthweight

Author: IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Laine, J.E., Bodinier, B., Robinson, O., Plusquin, M., Scalbert, A., Keski-Rahkonen, P., Robinot, N., Vermeulen, R., Pizzi, C., Asta, F., Nawrot, T., Gulliver, J., Chatzi, L., Kogevinas, M., Nieuwenhuijsen, M., Sunyer, J., Vrijheid, M., Chadeau-Hyam, M., Vineis, P., IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Laine, J.E., Bodinier, B., Robinson, O., Plusquin, M., Scalbert, A., Keski-Rahkonen, P., Robinot, N., Vermeulen, R., Pizzi, C., Asta, F., Nawrot, T., Gulliver, J., Chatzi, L., Kogevinas, M., Nieuwenhuijsen, M., Sunyer, J., Vrijheid, M., Chadeau-Hyam, M., and Vineis, P.
Published: 2020

27. A metabolomic study of red and processed meat intake and acylcarnitine concentrations in human urine and blood

Author: IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Wedekind, R., Kiss, A., Keski-Rahkonen, P., Viallon, V., Rothwell, J.A., Cross, A.J., Rostgaard-Hansen, A.L., Sandanger, T.M., Jakszyn, P., Pala, V., Vermeulen, R., Schulze, M.B., Kühn, T., Johnson, T., Trichopoulou, A., Peppa, E., Vechia, C.L., Masala, G., Tumino, R., Sacerdote, C., Wittenbecher, C., de Magistris, M.S., Dahm, C.C., Severi, G., Mancini, F.R., Weiderpass, E., Gunter, M.J., Huybrechts, I., Scalbert, A., IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Wedekind, R., Kiss, A., Keski-Rahkonen, P., Viallon, V., Rothwell, J.A., Cross, A.J., Rostgaard-Hansen, A.L., Sandanger, T.M., Jakszyn, P., Pala, V., Vermeulen, R., Schulze, M.B., Kühn, T., Johnson, T., Trichopoulou, A., Peppa, E., Vechia, C.L., Masala, G., Tumino, R., Sacerdote, C., Wittenbecher, C., de Magistris, M.S., Dahm, C.C., Severi, G., Mancini, F.R., Weiderpass, E., Gunter, M.J., Huybrechts, I., and Scalbert, A.
Published: 2020

28. A multi-omic analysis of birthweight in newborn cord blood reveals new underlying mechanisms related to cholesterol metabolism

Author: IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Alfano, R., Chadeau-Hyam, M., Ghantous, A., Keski-Rahkonen, P., Chatzi, L., Perez, A.E., Herceg, Z., Kogevinas, M., de Kok, T.M., Nawrot, T.S., Novoloaca, A., Patel, C.J., Pizzi, C., Robinot, N., Rusconi, F., Scalbert, A., Sunyer, J., Vermeulen, R., Vrijheid, M., Vineis, P., Robinson, O., Plusquin, M., IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Alfano, R., Chadeau-Hyam, M., Ghantous, A., Keski-Rahkonen, P., Chatzi, L., Perez, A.E., Herceg, Z., Kogevinas, M., de Kok, T.M., Nawrot, T.S., Novoloaca, A., Patel, C.J., Pizzi, C., Robinot, N., Rusconi, F., Scalbert, A., Sunyer, J., Vermeulen, R., Vrijheid, M., Vineis, P., Robinson, O., and Plusquin, M.
Published: 2020

29. A metabolomic study of red and processed meat intake and acylcarnitine concentrations in human urine and blood

Author: IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Wedekind, R., Kiss, A., Keski-Rahkonen, P., Viallon, V., Rothwell, J.A., Cross, A.J., Rostgaard-Hansen, A.L., Sandanger, T.M., Jakszyn, P., Pala, V., Vermeulen, R., Schulze, M.B., Kühn, T., Johnson, T., Trichopoulou, A., Peppa, E., Vechia, C.L., Masala, G., Tumino, R., Sacerdote, C., Wittenbecher, C., de Magistris, M.S., Dahm, C.C., Severi, G., Mancini, F.R., Weiderpass, E., Gunter, M.J., Huybrechts, I., Scalbert, A., IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Wedekind, R., Kiss, A., Keski-Rahkonen, P., Viallon, V., Rothwell, J.A., Cross, A.J., Rostgaard-Hansen, A.L., Sandanger, T.M., Jakszyn, P., Pala, V., Vermeulen, R., Schulze, M.B., Kühn, T., Johnson, T., Trichopoulou, A., Peppa, E., Vechia, C.L., Masala, G., Tumino, R., Sacerdote, C., Wittenbecher, C., de Magistris, M.S., Dahm, C.C., Severi, G., Mancini, F.R., Weiderpass, E., Gunter, M.J., Huybrechts, I., and Scalbert, A.
Published: 2020

30. Prenatal Exposure to Multiple Air Pollutants, Mediating Molecular Mechanisms, and Shifts in Birthweight

Author: IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Laine, J.E., Bodinier, B., Robinson, O., Plusquin, M., Scalbert, A., Keski-Rahkonen, P., Robinot, N., Vermeulen, R., Pizzi, C., Asta, F., Nawrot, T., Gulliver, J., Chatzi, L., Kogevinas, M., Nieuwenhuijsen, M., Sunyer, J., Vrijheid, M., Chadeau-Hyam, M., Vineis, P., IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Laine, J.E., Bodinier, B., Robinson, O., Plusquin, M., Scalbert, A., Keski-Rahkonen, P., Robinot, N., Vermeulen, R., Pizzi, C., Asta, F., Nawrot, T., Gulliver, J., Chatzi, L., Kogevinas, M., Nieuwenhuijsen, M., Sunyer, J., Vrijheid, M., Chadeau-Hyam, M., and Vineis, P.
Published: 2020

31. A multi-omic analysis of birthweight in newborn cord blood reveals new underlying mechanisms related to cholesterol metabolism

Author: IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Alfano, R., Chadeau-Hyam, M., Ghantous, A., Keski-Rahkonen, P., Chatzi, L., Perez, A.E., Herceg, Z., Kogevinas, M., de Kok, T.M., Nawrot, T.S., Novoloaca, A., Patel, C.J., Pizzi, C., Robinot, N., Rusconi, F., Scalbert, A., Sunyer, J., Vermeulen, R., Vrijheid, M., Vineis, P., Robinson, O., Plusquin, M., IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Alfano, R., Chadeau-Hyam, M., Ghantous, A., Keski-Rahkonen, P., Chatzi, L., Perez, A.E., Herceg, Z., Kogevinas, M., de Kok, T.M., Nawrot, T.S., Novoloaca, A., Patel, C.J., Pizzi, C., Robinot, N., Rusconi, F., Scalbert, A., Sunyer, J., Vermeulen, R., Vrijheid, M., Vineis, P., Robinson, O., and Plusquin, M.
Published: 2020

32. Plasma metabolites associated with colorectal cancer: A discovery-replication strategy

Author: Geijsen, A., Brezina, S., Keski-Rahkonen, P., Baierl, A., Bachleitner-Hofmann, T., Bergmann, M.M., Boehm, J., Brenner, H., Chang-Claude, J., Duijnhoven, F. J. B. van, Gigic, B., Gumpenberger, T., Hofer, P., Hoffmeister, M., Holowatyj, A.N., Karner-Hanusch, J., Kok, D.E., Leeb, G., Ulvik, A., Robinot, N., Ose, J., Stift, A., Schrotz-King, P., Ulrich, A.B., Ueland, P.M., Kampman, E., Scalbert, A., Habermann, N., Gsur, A., Ulrich, C.M., Geijsen, A., Brezina, S., Keski-Rahkonen, P., Baierl, A., Bachleitner-Hofmann, T., Bergmann, M.M., Boehm, J., Brenner, H., Chang-Claude, J., Duijnhoven, F. J. B. van, Gigic, B., Gumpenberger, T., Hofer, P., Hoffmeister, M., Holowatyj, A.N., Karner-Hanusch, J., Kok, D.E., Leeb, G., Ulvik, A., Robinot, N., Ose, J., Stift, A., Schrotz-King, P., Ulrich, A.B., Ueland, P.M., Kampman, E., Scalbert, A., Habermann, N., Gsur, A., and Ulrich, C.M.
Abstract: Contains fulltext : 208825.pdf (publisher's version ) (Open Access), Colorectal cancer is known to arise from multiple tumorigenic pathways; however, the underlying mechanisms remain not completely understood. Metabolomics is becoming an increasingly popular tool in assessing biological processes. Previous metabolomics research focusing on colorectal cancer is limited by sample size and did not replicate findings in independent study populations to verify robustness of reported findings. Here, we performed a ultrahigh performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) screening on EDTA plasma from 268 colorectal cancer patients and 353 controls using independent discovery and replication sets from two European cohorts (ColoCare Study: n = 180 patients/n = 153 controls; the Colorectal Cancer Study of Austria (CORSA) n = 88 patients/n = 200 controls), aiming to identify circulating plasma metabolites associated with colorectal cancer and to improve knowledge regarding colorectal cancer etiology. Multiple logistic regression models were used to test the association between disease state and metabolic features. Statistically significant associated features in the discovery set were taken forward and tested in the replication set to assure robustness of our findings. All models were adjusted for sex, age, BMI and smoking status and corrected for multiple testing using False Discovery Rate. Demographic and clinical data were abstracted from questionnaires and medical records.
Published: 2019

33. Plasma metabolites associated with colorectal cancer: A discovery-replication strategy

Author: Geijsen, A., Brezina, S., Keski-Rahkonen, P., Baierl, A., Bachleitner-Hofmann, T., Bergmann, M.M., Boehm, J., Brenner, H., Chang-Claude, J., Duijnhoven, F. J. B. van, Gigic, B., Gumpenberger, T., Hofer, P., Hoffmeister, M., Holowatyj, A.N., Karner-Hanusch, J., Kok, D.E., Leeb, G., Ulvik, A., Robinot, N., Ose, J., Stift, A., Schrotz-King, P., Ulrich, A.B., Ueland, P.M., Kampman, E., Scalbert, A., Habermann, N., Gsur, A., Ulrich, C.M., Geijsen, A., Brezina, S., Keski-Rahkonen, P., Baierl, A., Bachleitner-Hofmann, T., Bergmann, M.M., Boehm, J., Brenner, H., Chang-Claude, J., Duijnhoven, F. J. B. van, Gigic, B., Gumpenberger, T., Hofer, P., Hoffmeister, M., Holowatyj, A.N., Karner-Hanusch, J., Kok, D.E., Leeb, G., Ulvik, A., Robinot, N., Ose, J., Stift, A., Schrotz-King, P., Ulrich, A.B., Ueland, P.M., Kampman, E., Scalbert, A., Habermann, N., Gsur, A., and Ulrich, C.M.
Abstract: Contains fulltext : 208825.pdf (publisher's version ) (Open Access), Colorectal cancer is known to arise from multiple tumorigenic pathways; however, the underlying mechanisms remain not completely understood. Metabolomics is becoming an increasingly popular tool in assessing biological processes. Previous metabolomics research focusing on colorectal cancer is limited by sample size and did not replicate findings in independent study populations to verify robustness of reported findings. Here, we performed a ultrahigh performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) screening on EDTA plasma from 268 colorectal cancer patients and 353 controls using independent discovery and replication sets from two European cohorts (ColoCare Study: n = 180 patients/n = 153 controls; the Colorectal Cancer Study of Austria (CORSA) n = 88 patients/n = 200 controls), aiming to identify circulating plasma metabolites associated with colorectal cancer and to improve knowledge regarding colorectal cancer etiology. Multiple logistic regression models were used to test the association between disease state and metabolic features. Statistically significant associated features in the discovery set were taken forward and tested in the replication set to assure robustness of our findings. All models were adjusted for sex, age, BMI and smoking status and corrected for multiple testing using False Discovery Rate. Demographic and clinical data were abstracted from questionnaires and medical records.
Published: 2019

34. Plasma metabolites associated with colorectal cancer: A discovery-replication strategy

Author: Geijsen, A., Brezina, S., Keski-Rahkonen, P., Baierl, A., Bachleitner-Hofmann, T., Bergmann, M.M., Boehm, J., Brenner, H., Chang-Claude, J., Duijnhoven, F. J. B. van, Gigic, B., Gumpenberger, T., Hofer, P., Hoffmeister, M., Holowatyj, A.N., Karner-Hanusch, J., Kok, D.E., Leeb, G., Ulvik, A., Robinot, N., Ose, J., Stift, A., Schrotz-King, P., Ulrich, A.B., Ueland, P.M., Kampman, E., Scalbert, A., Habermann, N., Gsur, A., Ulrich, C.M., Geijsen, A., Brezina, S., Keski-Rahkonen, P., Baierl, A., Bachleitner-Hofmann, T., Bergmann, M.M., Boehm, J., Brenner, H., Chang-Claude, J., Duijnhoven, F. J. B. van, Gigic, B., Gumpenberger, T., Hofer, P., Hoffmeister, M., Holowatyj, A.N., Karner-Hanusch, J., Kok, D.E., Leeb, G., Ulvik, A., Robinot, N., Ose, J., Stift, A., Schrotz-King, P., Ulrich, A.B., Ueland, P.M., Kampman, E., Scalbert, A., Habermann, N., Gsur, A., and Ulrich, C.M.
Abstract: Contains fulltext : 208825.pdf (publisher's version ) (Open Access), Colorectal cancer is known to arise from multiple tumorigenic pathways; however, the underlying mechanisms remain not completely understood. Metabolomics is becoming an increasingly popular tool in assessing biological processes. Previous metabolomics research focusing on colorectal cancer is limited by sample size and did not replicate findings in independent study populations to verify robustness of reported findings. Here, we performed a ultrahigh performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) screening on EDTA plasma from 268 colorectal cancer patients and 353 controls using independent discovery and replication sets from two European cohorts (ColoCare Study: n = 180 patients/n = 153 controls; the Colorectal Cancer Study of Austria (CORSA) n = 88 patients/n = 200 controls), aiming to identify circulating plasma metabolites associated with colorectal cancer and to improve knowledge regarding colorectal cancer etiology. Multiple logistic regression models were used to test the association between disease state and metabolic features. Statistically significant associated features in the discovery set were taken forward and tested in the replication set to assure robustness of our findings. All models were adjusted for sex, age, BMI and smoking status and corrected for multiple testing using False Discovery Rate. Demographic and clinical data were abstracted from questionnaires and medical records.
Published: 2019

35. Perturbation of metabolic pathways mediates the association of air pollutants with asthma and cardiovascular diseases

Author: Jeong, A., Fiorito, G., Keski-Rahkonen, P., Imboden, M., Kiss, A., Robinot, N., Gmuender, H., Vlaanderen, J., Vermeulen, R., Kyrtopoulos, S., Herceg, Z., Ghantous, A., Lovison, G., Galassi, C., Ranzi, A., Krogh, V., Grioni, S., Agnoli, C., Sacerdote, C., Mostafavi, N., Naccarati, A., Scalbert, A., Vineis, P., Probst-Hensch, N., EXPOsOMICS consortium‡, Jeong, A., Fiorito, G., Keski-Rahkonen, P., Imboden, M., Kiss, A., Robinot, N., Gmuender, H., Vlaanderen, J., Vermeulen, R., Kyrtopoulos, S., Herceg, Z., Ghantous, A., Lovison, G., Galassi, C., Ranzi, A., Krogh, V., Grioni, S., Agnoli, C., Sacerdote, C., Mostafavi, N., Naccarati, A., Scalbert, A., Vineis, P., Probst-Hensch, N., and EXPOsOMICS consortium‡
Abstract: © 2018 The Authors Background: Epidemiologic evidence indicates common risk factors, including air pollution exposure, for respiratory and cardiovascular diseases, suggesting the involvement of common altered molecular pathways. Objectives: The goal was to find intermediate metabolites or metabolic pathways that could be associated with both air pollutants and health outcomes (“meeting-in-the-middle”), thus shedding light on mechanisms and reinforcing causality. Methods: We applied a statistical approach named ‘meet-in-the-middle’ to untargeted metabolomics in two independent case-control studies nested in cohorts on adult-onset asthma (AOA) and cardio-cerebrovascular diseases (CCVD). We compared the results to identify both common and disease-specific altered metabolic pathways. Results: A novel finding was a strong association of AOA with ultrafine particles (UFP; odds ratio 1.80 [1.26, 2.55] per increase by 5000 particles/cm3). Further, we have identified several metabolic pathways that potentially mediate the effect of air pollution on health outcomes. Among those, perturbation of Linoleate metabolism pathway was associated with air pollution exposure, AOA and CCVD. Conclusions: Our results suggest common pathway perturbations may occur as a consequence of chronic exposure to air pollution leading to increased risk for both AOA and CCVD.
Published: 2018

36. Circulating plasma phospholipid fatty acids and risk of pancreatic cancer in a large European cohort

Author: Matejcic, M., Lesueur, F., Biessy, C., Renault, A. L., Mebirouk, N., Yammine, S., Keski-Rahkonen, P., Li, K., Hemon, B., Weiderpass, E., Rebours, V., Boutron-Ruault, M. C., Carbonnel, F., Kaaks, R., Katzke, V., Kuhn, T., Boeing, H., Trichopoulou, A., Palli, D., Agnoli, C., Panico, S., Tumino, R., Sacerdote, C., Quiros, J. R., Duell, E. J., Porta, M., Sanchez, M. J., Chirlaque, M. D., Barricarte, A., Amiano, P., Ye, Weimin, Peeters, P. H., Khaw, K. T., Perez-Cornago, A., Key, T. J., Bueno-de-Mesquita, H. B., Riboli, E., Vineis, P., Romieu, I., Gunter, M. J., Chajes, V., Matejcic, M., Lesueur, F., Biessy, C., Renault, A. L., Mebirouk, N., Yammine, S., Keski-Rahkonen, P., Li, K., Hemon, B., Weiderpass, E., Rebours, V., Boutron-Ruault, M. C., Carbonnel, F., Kaaks, R., Katzke, V., Kuhn, T., Boeing, H., Trichopoulou, A., Palli, D., Agnoli, C., Panico, S., Tumino, R., Sacerdote, C., Quiros, J. R., Duell, E. J., Porta, M., Sanchez, M. J., Chirlaque, M. D., Barricarte, A., Amiano, P., Ye, Weimin, Peeters, P. H., Khaw, K. T., Perez-Cornago, A., Key, T. J., Bueno-de-Mesquita, H. B., Riboli, E., Vineis, P., Romieu, I., Gunter, M. J., and Chajes, V.
Abstract: There are both limited and conflicting data on the role of dietary fat and specific fatty acids in the development of pancreatic cancer. In this study, we investigated the association between plasma phospholipid fatty acids and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The fatty acid composition was measured by gas chromatography in plasma samples collected at recruitment from375 incident pancreatic cancer cases and375 matched controls. Associations of specific fatty acids with pancreatic cancer risk were evaluated using multivariable conditional logistic regression models with adjustment for established pancreatic cancer risk factors. Statistically significant inverse associations were found between pancreatic cancer incidence and levels of heptadecanoic acid (ORT3‐T1[odds ratio for highest versus lowest tertile] =0.63; 95%CI[confidence interval] = 0.41–0.98; ptrend = 0.036), n‐3 polyunsaturated α‐linolenic acid (ORT3‐T1 = 0.60; 95%CI = 0.39–0.92; ptrend = 0.02) and docosapentaenoic acid (ORT3‐T1 = 0.52; 95%CI = 0.32–0.85; ptrend = 0.008). Industrial trans‐fatty acids were positively associated with pancreatic cancer risk among men (ORT3‐T1 = 3.00; 95%CI = 1.13–7.99; ptrend = 0.029), while conjugated linoleic acids were inversely related to pancreatic cancer among women only (ORT3‐T1 = 0.37; 95%CI = 0.17–0.81; ptrend = 0.008). Among current smokers, the long‐chain n‐6/n‐3 polyunsaturated fatty acids ratio was positively associated with pancreatic cancer risk (ORT3‐T1 = 3.40; 95%CI = 1.39–8.34; ptrend = 0.007). Results were robust to a range of sensitivity analyses. Our findings suggest that higher circulating levels of saturated fatty acids with an odd number of carbon atoms and n‐3 polyunsaturated fatty acids may be related to lower risk of pancreatic cancer. The influence of some fatty acids on the development of pancreatic cancer may be sex‐specific and modulated by smoking.
Published: 2018
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37. Circulating plasma phospholipid fatty acids and risk of pancreatic cancer in a large European cohort

Author: Matejcic, M., Lesueur, F., Biessy, C., Renault, A. L., Mebirouk, N., Yammine, S., Keski-Rahkonen, P., Li, K., Hémon, B., Weiderpass, E., Rebours, V., Boutron-Ruault, M. C., Carbonnel, F., Kaaks, R., Katzke, V., Kuhn, T., Boeing, H., Trichopoulou, A., Palli, D., Agnoli, C., Panico, S., Tumino, R., Sacerdote, C., Quirós, J. R., Duell, E. J., Porta, M., Sánchez, M. J., Chirlaque, M. D., Barricarte, A., Amiano, P., Ye, W., Peeters, P. H., Khaw, K. T., Perez-Cornago, A., Key, T. J., Bueno-de-Mesquita, H. B., Riboli, E., Vineis, P., Romieu, I., Gunter, M. J., Chajès, V., Matejcic, M., Lesueur, F., Biessy, C., Renault, A. L., Mebirouk, N., Yammine, S., Keski-Rahkonen, P., Li, K., Hémon, B., Weiderpass, E., Rebours, V., Boutron-Ruault, M. C., Carbonnel, F., Kaaks, R., Katzke, V., Kuhn, T., Boeing, H., Trichopoulou, A., Palli, D., Agnoli, C., Panico, S., Tumino, R., Sacerdote, C., Quirós, J. R., Duell, E. J., Porta, M., Sánchez, M. J., Chirlaque, M. D., Barricarte, A., Amiano, P., Ye, W., Peeters, P. H., Khaw, K. T., Perez-Cornago, A., Key, T. J., Bueno-de-Mesquita, H. B., Riboli, E., Vineis, P., Romieu, I., Gunter, M. J., and Chajès, V.
Published: 2018

38. Circulating plasma phospholipid fatty acids and risk of pancreatic cancer in a large European cohort

Author: Matejcic, M., Lesueur, F., Biessy, C., Renault, A. L., Mebirouk, N., Yammine, S., Keski-Rahkonen, P., Li, K., Hémon, B., Weiderpass, E., Rebours, V., Boutron-Ruault, M. C., Carbonnel, F., Kaaks, R., Katzke, V., Kuhn, T., Boeing, H., Trichopoulou, A., Palli, D., Agnoli, C., Panico, S., Tumino, R., Sacerdote, C., Quirós, J. R., Duell, E. J., Porta, M., Sánchez, M. J., Chirlaque, M. D., Barricarte, A., Amiano, P., Ye, W., Peeters, P. H., Khaw, K. T., Perez-Cornago, A., Key, T. J., Bueno-de-Mesquita, H. B., Riboli, E., Vineis, P., Romieu, I., Gunter, M. J., Chajès, V., Matejcic, M., Lesueur, F., Biessy, C., Renault, A. L., Mebirouk, N., Yammine, S., Keski-Rahkonen, P., Li, K., Hémon, B., Weiderpass, E., Rebours, V., Boutron-Ruault, M. C., Carbonnel, F., Kaaks, R., Katzke, V., Kuhn, T., Boeing, H., Trichopoulou, A., Palli, D., Agnoli, C., Panico, S., Tumino, R., Sacerdote, C., Quirós, J. R., Duell, E. J., Porta, M., Sánchez, M. J., Chirlaque, M. D., Barricarte, A., Amiano, P., Ye, W., Peeters, P. H., Khaw, K. T., Perez-Cornago, A., Key, T. J., Bueno-de-Mesquita, H. B., Riboli, E., Vineis, P., Romieu, I., Gunter, M. J., and Chajès, V.
Published: 2018

39. Perturbation of metabolic pathways mediates the association of air pollutants with asthma and cardiovascular diseases

Author: One Health Chemisch, dIRAS RA-2, Jeong, A., Fiorito, G., Keski-Rahkonen, P., Imboden, M., Kiss, A., Robinot, N., Gmuender, H., Vlaanderen, J., Vermeulen, R., Kyrtopoulos, S., Herceg, Z., Ghantous, A., Lovison, G., Galassi, C., Ranzi, A., Krogh, V., Grioni, S., Agnoli, C., Sacerdote, C., Mostafavi, N., Naccarati, A., Scalbert, A., Vineis, P., Probst-Hensch, N., EXPOsOMICS consortium‡, One Health Chemisch, dIRAS RA-2, Jeong, A., Fiorito, G., Keski-Rahkonen, P., Imboden, M., Kiss, A., Robinot, N., Gmuender, H., Vlaanderen, J., Vermeulen, R., Kyrtopoulos, S., Herceg, Z., Ghantous, A., Lovison, G., Galassi, C., Ranzi, A., Krogh, V., Grioni, S., Agnoli, C., Sacerdote, C., Mostafavi, N., Naccarati, A., Scalbert, A., Vineis, P., Probst-Hensch, N., and EXPOsOMICS consortium‡
Published: 2018

40. Circulating plasma phospholipid fatty acids and risk of pancreatic cancer in a large European cohort

Author: Matejcic, M., Lesueur, F., Biessy, C., Renault, A. L., Mebirouk, N., Yammine, S., Keski-Rahkonen, P., Li, K., Hémon, B., Weiderpass, E., Rebours, V., Boutron-Ruault, M. C., Carbonnel, F., Kaaks, R., Katzke, V., Kuhn, T., Boeing, H., Trichopoulou, A., Palli, D., Agnoli, C., Panico, S., Tumino, R., Sacerdote, C., Quirós, J. R., Duell, E. J., Porta, M., Sánchez, M. J., Chirlaque, M. D., Barricarte, A., Amiano, P., Ye, W., Peeters, P. H., Khaw, K. T., Perez-Cornago, A., Key, T. J., Bueno-de-Mesquita, H. B., Riboli, E., Vineis, P., Romieu, I., Gunter, M. J., Chajès, V., Matejcic, M., Lesueur, F., Biessy, C., Renault, A. L., Mebirouk, N., Yammine, S., Keski-Rahkonen, P., Li, K., Hémon, B., Weiderpass, E., Rebours, V., Boutron-Ruault, M. C., Carbonnel, F., Kaaks, R., Katzke, V., Kuhn, T., Boeing, H., Trichopoulou, A., Palli, D., Agnoli, C., Panico, S., Tumino, R., Sacerdote, C., Quirós, J. R., Duell, E. J., Porta, M., Sánchez, M. J., Chirlaque, M. D., Barricarte, A., Amiano, P., Ye, W., Peeters, P. H., Khaw, K. T., Perez-Cornago, A., Key, T. J., Bueno-de-Mesquita, H. B., Riboli, E., Vineis, P., Romieu, I., Gunter, M. J., and Chajès, V.
Published: 2018

41. Perturbation of metabolic pathways mediates the association of air pollutants with asthma and cardiovascular diseases

Author: One Health Chemisch, dIRAS RA-2, Jeong, A., Fiorito, G., Keski-Rahkonen, P., Imboden, M., Kiss, A., Robinot, N., Gmuender, H., Vlaanderen, J., Vermeulen, R., Kyrtopoulos, S., Herceg, Z., Ghantous, A., Lovison, G., Galassi, C., Ranzi, A., Krogh, V., Grioni, S., Agnoli, C., Sacerdote, C., Mostafavi, N., Naccarati, A., Scalbert, A., Vineis, P., Probst-Hensch, N., EXPOsOMICS consortium‡, One Health Chemisch, dIRAS RA-2, Jeong, A., Fiorito, G., Keski-Rahkonen, P., Imboden, M., Kiss, A., Robinot, N., Gmuender, H., Vlaanderen, J., Vermeulen, R., Kyrtopoulos, S., Herceg, Z., Ghantous, A., Lovison, G., Galassi, C., Ranzi, A., Krogh, V., Grioni, S., Agnoli, C., Sacerdote, C., Mostafavi, N., Naccarati, A., Scalbert, A., Vineis, P., Probst-Hensch, N., and EXPOsOMICS consortium‡
Published: 2018

42. Circulating plasma phospholipid fatty acids and risk of pancreatic cancer in a large European cohort

Author: JC onderzoeksprogramma Kanker, Cancer, Epi Kanker Team B, UMC Utrecht, Matejcic, M., Lesueur, F., Biessy, C., Renault, A. L., Mebirouk, N., Yammine, S., Keski-Rahkonen, P., Li, K., Hémon, B., Weiderpass, E., Rebours, V., Boutron-Ruault, M. C., Carbonnel, F., Kaaks, R., Katzke, V., Kuhn, T., Boeing, H., Trichopoulou, A., Palli, D., Agnoli, C., Panico, S., Tumino, R., Sacerdote, C., Quirós, J. R., Duell, E. J., Porta, M., Sánchez, M. J., Chirlaque, M. D., Barricarte, A., Amiano, P., Ye, W., Peeters, P. H., Khaw, K. T., Perez-Cornago, A., Key, T. J., Bueno-de-Mesquita, H. B., Riboli, E., Vineis, P., Romieu, I., Gunter, M. J., Chajès, V., JC onderzoeksprogramma Kanker, Cancer, Epi Kanker Team B, UMC Utrecht, Matejcic, M., Lesueur, F., Biessy, C., Renault, A. L., Mebirouk, N., Yammine, S., Keski-Rahkonen, P., Li, K., Hémon, B., Weiderpass, E., Rebours, V., Boutron-Ruault, M. C., Carbonnel, F., Kaaks, R., Katzke, V., Kuhn, T., Boeing, H., Trichopoulou, A., Palli, D., Agnoli, C., Panico, S., Tumino, R., Sacerdote, C., Quirós, J. R., Duell, E. J., Porta, M., Sánchez, M. J., Chirlaque, M. D., Barricarte, A., Amiano, P., Ye, W., Peeters, P. H., Khaw, K. T., Perez-Cornago, A., Key, T. J., Bueno-de-Mesquita, H. B., Riboli, E., Vineis, P., Romieu, I., Gunter, M. J., and Chajès, V.
Published: 2018

43. Perturbation of metabolic pathways mediates the association of air pollutants with asthma and cardiovascular diseases

Author: One Health Chemisch, dIRAS RA-2, Jeong, A., Fiorito, G., Keski-Rahkonen, P., Imboden, M., Kiss, A., Robinot, N., Gmuender, H., Vlaanderen, J., Vermeulen, R., Kyrtopoulos, S., Herceg, Z., Ghantous, A., Lovison, G., Galassi, C., Ranzi, A., Krogh, V., Grioni, S., Agnoli, C., Sacerdote, C., Mostafavi, N., Naccarati, A., Scalbert, A., Vineis, P., Probst-Hensch, N., EXPOsOMICS consortium‡, One Health Chemisch, dIRAS RA-2, Jeong, A., Fiorito, G., Keski-Rahkonen, P., Imboden, M., Kiss, A., Robinot, N., Gmuender, H., Vlaanderen, J., Vermeulen, R., Kyrtopoulos, S., Herceg, Z., Ghantous, A., Lovison, G., Galassi, C., Ranzi, A., Krogh, V., Grioni, S., Agnoli, C., Sacerdote, C., Mostafavi, N., Naccarati, A., Scalbert, A., Vineis, P., Probst-Hensch, N., and EXPOsOMICS consortium‡
Published: 2018

44. The impact of ambient air pollution on the human blood metabolome

Author: Vlaanderen, J.J., Janssen, N.A., Hoek, G., Keski-Rahkonen, P, Barupal, D K, Cassee, F.R., Gosens, I., Strak, M., Steenhof, M., Lan, Q., Brunekreef, B., Scalbert, Augustin, Vermeulen, R.C.H., Vlaanderen, J.J., Janssen, N.A., Hoek, G., Keski-Rahkonen, P, Barupal, D K, Cassee, F.R., Gosens, I., Strak, M., Steenhof, M., Lan, Q., Brunekreef, B., Scalbert, Augustin, and Vermeulen, R.C.H.
Abstract: BACKGROUND: Biological perturbations caused by air pollution might be reflected in the compounds present in blood originating from air pollutants and endogenous metabolites influenced by air pollution (defined here as part of the blood metabolome). We aimed to assess the perturbation of the blood metabolome in response to short term exposure to air pollution. METHODS: We exposed 31 healthy volunteers to ambient air pollution for 5h. We measured exposure to particulate matter, particle number concentrations, absorbance, elemental/organic carbon, trace metals, secondary inorganic components, endotoxin content, gaseous pollutants, and particulate matter oxidative potential. We collected blood from the participants 2h before and 2 and 18h after exposure. We employed untargeted metabolite profiling to monitor 3873 metabolic features in 493 blood samples from these volunteers. We assessed lung function using spirometry and six acute phase proteins in peripheral blood. We assessed the association of the metabolic features with the measured air pollutants and with health markers that we previously observed to be associated with air pollution in this study. RESULTS: We observed 89 robust associations between air pollutants and metabolic features two hours after exposure and 118 robust associations 18h after exposure. Some of the metabolic features that were associated with air pollutants were also associated with acute health effects, especially changes in forced expiratory volume in 1s. We successfully identified tyrosine, guanosine, and hypoxanthine among the associated features. Bioinformatics approach Mummichog predicted enriched pathway activity in eight pathways, among which tyrosine metabolism. CONCLUSIONS: This study demonstrates for the first time the application of untargeted metabolite profiling to assess the impact of air pollution on the blood metabolome.
Published: 2017

45. The impact of ambient air pollution on the human blood metabolome

Author: LS IRAS EEPI GRA (Gezh.risico-analyse), Dep IRAS, LS IRAS EEPI ME (Milieu epidemiologie), LS IRAS EEPI Inhalatie Toxicologie, Sub IRAS Tox ITX (immunotoxicologie), dIRAS RA-2, dIRAS RA-1, Vlaanderen, J.J., Janssen, N.A., Hoek, G., Keski-Rahkonen, P, Barupal, D K, Cassee, F.R., Gosens, I., Strak, M., Steenhof, M., Lan, Q., Brunekreef, B., Scalbert, Augustin, Vermeulen, R.C.H., LS IRAS EEPI GRA (Gezh.risico-analyse), Dep IRAS, LS IRAS EEPI ME (Milieu epidemiologie), LS IRAS EEPI Inhalatie Toxicologie, Sub IRAS Tox ITX (immunotoxicologie), dIRAS RA-2, dIRAS RA-1, Vlaanderen, J.J., Janssen, N.A., Hoek, G., Keski-Rahkonen, P, Barupal, D K, Cassee, F.R., Gosens, I., Strak, M., Steenhof, M., Lan, Q., Brunekreef, B., Scalbert, Augustin, and Vermeulen, R.C.H.
Published: 2017

46. The impact of ambient air pollution on the human blood metabolome

Author: LS IRAS EEPI GRA (Gezh.risico-analyse), Dep IRAS, LS IRAS EEPI ME (Milieu epidemiologie), LS IRAS EEPI Inhalatie Toxicologie, Sub IRAS Tox ITX (immunotoxicologie), dIRAS RA-2, dIRAS RA-1, Vlaanderen, J.J., Janssen, N.A., Hoek, G., Keski-Rahkonen, P, Barupal, D K, Cassee, F.R., Gosens, I., Strak, M., Steenhof, M., Lan, Q., Brunekreef, B., Scalbert, Augustin, Vermeulen, R.C.H., LS IRAS EEPI GRA (Gezh.risico-analyse), Dep IRAS, LS IRAS EEPI ME (Milieu epidemiologie), LS IRAS EEPI Inhalatie Toxicologie, Sub IRAS Tox ITX (immunotoxicologie), dIRAS RA-2, dIRAS RA-1, Vlaanderen, J.J., Janssen, N.A., Hoek, G., Keski-Rahkonen, P, Barupal, D K, Cassee, F.R., Gosens, I., Strak, M., Steenhof, M., Lan, Q., Brunekreef, B., Scalbert, Augustin, and Vermeulen, R.C.H.
Published: 2017

47. The impact of ambient air pollution on the human blood metabolome

Author: LS IRAS EEPI GRA (Gezh.risico-analyse), Dep IRAS, LS IRAS EEPI ME (Milieu epidemiologie), LS IRAS EEPI Inhalatie Toxicologie, Sub IRAS Tox ITX (immunotoxicologie), dIRAS RA-2, dIRAS RA-1, Vlaanderen, J.J., Janssen, N.A., Hoek, G., Keski-Rahkonen, P, Barupal, D K, Cassee, F.R., Gosens, I., Strak, M., Steenhof, M., Lan, Q., Brunekreef, B., Scalbert, Augustin, Vermeulen, R.C.H., LS IRAS EEPI GRA (Gezh.risico-analyse), Dep IRAS, LS IRAS EEPI ME (Milieu epidemiologie), LS IRAS EEPI Inhalatie Toxicologie, Sub IRAS Tox ITX (immunotoxicologie), dIRAS RA-2, dIRAS RA-1, Vlaanderen, J.J., Janssen, N.A., Hoek, G., Keski-Rahkonen, P, Barupal, D K, Cassee, F.R., Gosens, I., Strak, M., Steenhof, M., Lan, Q., Brunekreef, B., Scalbert, Augustin, and Vermeulen, R.C.H.
Published: 2017

48. Границы распространения мерянско-муромских и древнемордовских гидронимов в верховьях Волги и бассейне Оки

Author: Рахконен, П., Rahkonen, P., Рахконен, П., and Rahkonen, P.
Abstract: The article explores the toponymy of the Merya, Muromians and Old Mordvins, Finno-Ugric peoples, formerly inhabiting Central Russia. With reference to annalistic and archaeological data, along with a number of the most representative attributes and formants, the author concludes that the Merya and Muromian languages were kindred and localized within the boundaries of five areas, namely, Rostov-Kostroma, Murom, Dyakovo, North Lake District, and northern periphery. According the author, Old Mordvins settled a lot farther west than do modern Mordvins., В статье рассматривается топонимия мери, муромы и древней мордвы – финно-угорских народов, населявших в прошлом регион Центральной России. Опираясь на летописные и археологические данные, а также на ряд наиболее показательных топонимических атрибутов и формантов, автор заключает, что мерянский и муромский языки являлись близкородственными и были локализованы в пяти ареалах: ростовско-костромском, муромском, дьяковском, северном озерном крае и северной периферии. Древняя мордва, согласно выводам автора, была расселена значительно западнее современной территории проживания мордвы.
Published: 2012

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