244 results on '"Gicquiau, A."'
Search Results
2. Circulating amino acid levels and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition and UK Biobank cohorts
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Rothwell, Joseph A., Bešević, Jelena, Dimou, Niki, Breeur, Marie, Murphy, Neil, Jenab, Mazda, Wedekind, Roland, Viallon, Vivian, Ferrari, Pietro, Achaintre, David, Gicquiau, Audrey, Rinaldi, Sabina, Scalbert, Augustin, Huybrechts, Inge, Prehn, Cornelia, Adamski, Jerzy, Cross, Amanda J., Keun, Hector, Chadeau-Hyam, Marc, Boutron-Ruault, Marie-Christine, Overvad, Kim, Dahm, Christina C., Nøst, Therese Haugdahl, Sandanger, Torkjel M., Skeie, Guri, Zamora-Ros, Raul, Tsilidis, Kostas K., Eichelmann, Fabian, Schulze, Matthias B., van Guelpen, Bethany, Vidman, Linda, Sánchez, Maria-José, Amiano, Pilar, Ardanaz, Eva, Smith-Byrne, Karl, Travis, Ruth, Katzke, Verena, Kaaks, Rudolf, Derksen, Jeroen W. G., Colorado-Yohar, Sandra, Tumino, Rosario, Bueno-de-Mesquita, Bas, Vineis, Paolo, Palli, Domenico, Pasanisi, Fabrizio, Eriksen, Anne Kirstine, Tjønneland, Anne, Severi, Gianluca, and Gunter, Marc J.
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- 2023
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3. Association between pre-diagnostic circulating lipid metabolites and colorectal cancer risk: a nested case–control study in the European Prospective Investigation into Cancer and Nutrition (EPIC)Research in context
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Rhea Harewood, Joseph A. Rothwell, Jelena Bešević, Vivian Viallon, David Achaintre, Audrey Gicquiau, Sabina Rinaldi, Roland Wedekind, Cornelia Prehn, Jerzy Adamski, Julie A. Schmidt, Inarie Jacobs, Anne Tjønneland, Anja Olsen, Gianluca Severi, Rudolf Kaaks, Verena Katzke, Matthias B. Schulze, Marcela Prada, Giovanna Masala, Claudia Agnoli, Salvatore Panico, Carlotta Sacerdote, Paula Gabriela Jakszyn, Maria-Jose Sánchez, Jesús Castilla, María-Dolores Chirlaque, Amaia Aizpurua Atxega, Bethany van Guelpen, Alicia K. Heath, Keren Papier, Tammy Y.N. Tong, Scott A. Summers, Mary Playdon, Amanda J. Cross, Pekka Keski-Rahkonen, Véronique Chajès, Neil Murphy, and Marc J. Gunter
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Colorectal cancer ,Metabolomics ,Lipids ,Glycerophospholipids ,Sphingolipids ,Acylcarnitines ,Medicine ,Medicine (General) ,R5-920 - Abstract
Summary: Background: Altered lipid metabolism is a hallmark of cancer development. However, the role of specific lipid metabolites in colorectal cancer development is uncertain. Methods: In a case–control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), we examined associations between pre-diagnostic circulating concentrations of 97 lipid metabolites (acylcarnitines, glycerophospholipids and sphingolipids) and colorectal cancer risk. Circulating lipids were measured using targeted mass spectrometry in 1591 incident colorectal cancer cases (55% women) and 1591 matched controls. Multivariable conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between concentrations of individual lipid metabolites and metabolite patterns with colorectal cancer risk. Findings: Of the 97 assayed lipids, 24 were inversely associated (nominally p
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- 2024
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4. Association between pre-diagnostic circulating lipid metabolites and colorectal cancer risk: a nested case–control study in the European Prospective Investigation into Cancer and Nutrition (EPIC)
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Harewood, Rhea, Rothwell, Joseph A., Bešević, Jelena, Viallon, Vivian, Achaintre, David, Gicquiau, Audrey, Rinaldi, Sabina, Wedekind, Roland, Prehn, Cornelia, Adamski, Jerzy, Schmidt, Julie A., Jacobs, Inarie, Tjønneland, Anne, Olsen, Anja, Severi, Gianluca, Kaaks, Rudolf, Katzke, Verena, Schulze, Matthias B., Prada, Marcela, Masala, Giovanna, Agnoli, Claudia, Panico, Salvatore, Sacerdote, Carlotta, Jakszyn, Paula Gabriela, Sánchez, Maria-Jose, Castilla, Jesús, Chirlaque, María-Dolores, Atxega, Amaia Aizpurua, van Guelpen, Bethany, Heath, Alicia K., Papier, Keren, Tong, Tammy Y.N., Summers, Scott A., Playdon, Mary, Cross, Amanda J., Keski-Rahkonen, Pekka, Chajès, Véronique, Murphy, Neil, and Gunter, Marc J.
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- 2024
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5. Circulating amino acid levels and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition and UK Biobank cohorts
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Joseph A. Rothwell, Jelena Bešević, Niki Dimou, Marie Breeur, Neil Murphy, Mazda Jenab, Roland Wedekind, Vivian Viallon, Pietro Ferrari, David Achaintre, Audrey Gicquiau, Sabina Rinaldi, Augustin Scalbert, Inge Huybrechts, Cornelia Prehn, Jerzy Adamski, Amanda J. Cross, Hector Keun, Marc Chadeau-Hyam, Marie-Christine Boutron-Ruault, Kim Overvad, Christina C. Dahm, Therese Haugdahl Nøst, Torkjel M. Sandanger, Guri Skeie, Raul Zamora-Ros, Kostas K. Tsilidis, Fabian Eichelmann, Matthias B. Schulze, Bethany van Guelpen, Linda Vidman, Maria-José Sánchez, Pilar Amiano, Eva Ardanaz, Karl Smith-Byrne, Ruth Travis, Verena Katzke, Rudolf Kaaks, Jeroen W. G. Derksen, Sandra Colorado-Yohar, Rosario Tumino, Bas Bueno-de-Mesquita, Paolo Vineis, Domenico Palli, Fabrizio Pasanisi, Anne Kirstine Eriksen, Anne Tjønneland, Gianluca Severi, and Marc J. Gunter
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Colorectal cancer ,Amino acids ,Glutamine ,Histidine ,Medicine - Abstract
Abstract Background Amino acid metabolism is dysregulated in colorectal cancer patients; however, it is not clear whether pre-diagnostic levels of amino acids are associated with subsequent risk of colorectal cancer. We investigated circulating levels of amino acids in relation to colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) and UK Biobank cohorts. Methods Concentrations of 13-21 amino acids were determined in baseline fasting plasma or serum samples in 654 incident colorectal cancer cases and 654 matched controls in EPIC. Amino acids associated with colorectal cancer risk following adjustment for the false discovery rate (FDR) were then tested for associations in the UK Biobank, for which measurements of 9 amino acids were available in 111,323 participants, of which 1221 were incident colorectal cancer cases. Results Histidine levels were inversely associated with colorectal cancer risk in EPIC (odds ratio [OR] 0.80 per standard deviation [SD], 95% confidence interval [CI] 0.69–0.92, FDR P-value=0.03) and in UK Biobank (HR 0.93 per SD, 95% CI 0.87–0.99, P-value=0.03). Glutamine levels were borderline inversely associated with colorectal cancer risk in EPIC (OR 0.85 per SD, 95% CI 0.75–0.97, FDR P-value=0.08) and similarly in UK Biobank (HR 0.95, 95% CI 0.89–1.01, P=0.09) In both cohorts, associations changed only minimally when cases diagnosed within 2 or 5 years of follow-up were excluded. Conclusions Higher circulating levels of histidine were associated with a lower risk of colorectal cancer in two large prospective cohorts. Further research to ascertain the role of histidine metabolism and potentially that of glutamine in colorectal cancer development is warranted.
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- 2023
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6. Metabolic Signatures of Healthy Lifestyle Patterns and Colorectal Cancer Risk in a European Cohort
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Rothwell, Joseph A., Murphy, Neil, Bešević, Jelena, Kliemann, Nathalie, Jenab, Mazda, Ferrari, Pietro, Achaintre, David, Gicquiau, Audrey, Vozar, Béatrice, Scalbert, Augustin, Huybrechts, Inge, Freisling, Heinz, Prehn, Cornelia, Adamski, Jerzy, Cross, Amanda J., Pala, Valeria Maria, Boutron-Ruault, Marie-Christine, Dahm, Christina C., Overvad, Kim, Gram, Inger Torhild, Sandanger, Torkjel M., Skeie, Guri, Jakszyn, Paula, Tsilidis, Kostas K., Aleksandrova, Krasimira, Schulze, Matthias B., Hughes, David J., van Guelpen, Bethany, Bodén, Stina, Sánchez, Maria-José, Schmidt, Julie A., Katzke, Verena, Kühn, Tilman, Colorado-Yohar, Sandra, Tumino, Rosario, Bueno-de-Mesquita, Bas, Vineis, Paolo, Masala, Giovanna, Panico, Salvatore, Eriksen, Anne Kirstine, Tjønneland, Anne, Aune, Dagfinn, Weiderpass, Elisabete, Severi, Gianluca, Chajès, Véronique, and Gunter, Marc J.
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- 2022
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7. Diet quality indices and dietary patterns are associated with plasma metabolites in colorectal cancer patients
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Geijsen, Anne J. M. R., Kok, Dieuwertje E., van Zutphen, Moniek, Keski-Rahkonen, Pekka, Achaintre, David, Gicquiau, Audrey, Gsur, Andrea, Kruyt, Flip M., Ulrich, Cornelia M., Weijenberg, Matty P., de Wilt, Johannes H. W ., Wesselink, Evertine, Scalbert, Augustin, Kampman, Ellen, and van Duijnhoven, Fränzel J. B.
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- 2021
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8. Higher Plasma Creatinine Is Associated with an Increased Risk of Death in Patients with Non-Metastatic Rectal but Not Colon Cancer: Results from an International Cohort Consortium
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Jennifer Ose, Biljana Gigic, Stefanie Brezina, Tengda Lin, Anita R. Peoples, Pauline P. Schobert, Andreas Baierl, Eline van Roekel, Nivonirina Robinot, Audrey Gicquiau, David Achaintre, Augustin Scalbert, Fränzel J. B. van Duijnhoven, Andreana N. Holowatyj, Tanja Gumpenberger, Petra Schrotz-King, Alexis B. Ulrich, Arve Ulvik, Per-Magne Ueland, Matty P. Weijenberg, Nina Habermann, Pekka Keski-Rahkonen, Andrea Gsur, Dieuwertje E. Kok, and Cornelia M. Ulrich
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all-cause mortality ,creatinine ,metabolites ,colon cancer ,rectal cancer ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Colorectal cancer (CRC) is increasingly recognized as a heterogeneous disease. No studies have prospectively examined associations of blood metabolite concentrations with all-cause mortality in patients with colon and rectal cancer separately. Targeted metabolomics (Biocrates AbsoluteIDQ p180) and pathway analyses (MetaboAnalyst 4.0) were performed on pre-surgery collected plasma from 674 patients with non-metastasized (stage I–III) colon (n = 394) or rectal cancer (n = 283). Metabolomics data and covariate information were received from the international cohort consortium MetaboCCC. Cox proportional hazards models were computed to investigate associations of 148 metabolite levels with all-cause mortality adjusted for age, sex, tumor stage, tumor site (whenever applicable), and cohort; the false discovery rate (FDR) was used to account for multiple testing. A total of 93 patients (14%) were deceased after an average follow-up time of 4.4 years (60 patients with colon cancer and 33 patients with rectal cancer). After FDR adjustment, higher plasma creatinine was associated with a 39% increase in all-cause mortality in patients with rectal cancer. HR: 1.39, 95% CI 1.23–1.72, pFDR = 0.03; but not colon cancer: pFDR = 0.96. Creatinine is a breakdown product of creatine phosphate in muscle and may reflect changes in skeletal muscle mass. The starch and sucrose metabolisms were associated with increased all-cause mortality in colon cancer but not in rectal cancer. Genes in the starch and sucrose metabolism pathways were previously linked to worse clinical outcomes in CRC. In summary, our findings support the hypothesis that colon and rectal cancer have different etiological and clinical outcomes that need to be considered for targeted treatments.
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- 2023
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9. Biomarkers of mammographic density in premenopausal women
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Mathilde His, Martin Lajous, Liliana Gómez-Flores-Ramos, Adriana Monge, Laure Dossus, Vivian Viallon, Audrey Gicquiau, Carine Biessy, Marc J. Gunter, and Sabina Rinaldi
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Mammographic density ,Premenopausal ,Mexican women ,Targeted metabolomics ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background While mammographic density is one of the strongest risk factors for breast cancer, little is known about its determinants, especially in young women. We applied targeted metabolomics to identify circulating metabolites specifically associated with mammographic density in premenopausal women. Then, we aimed to identify potential correlates of these biomarkers to guide future research on potential modifiable determinants of mammographic density. Methods A total of 132 metabolites (acylcarnitines, amino acids, biogenic amines, glycerophospholipids, sphingolipids, hexose) were measured by tandem liquid chromatography/mass spectrometry in plasma samples from 573 premenopausal participants in the Mexican Teachers’ Cohort. Associations between metabolites and percent mammographic density were assessed using linear regression models, adjusting for breast cancer risk factors and accounting for multiple tests. Mean concentrations of metabolites associated with percent mammographic density were estimated across levels of several lifestyle and metabolic factors. Results Sphingomyelin (SM) C16:1 and phosphatidylcholine (PC) ae C30:2 were inversely associated with percent mammographic density after correction for multiple tests. Linear trends with percent mammographic density were observed for SM C16:1 only in women with body mass index (BMI) below the median (27.4) and for PC ae C30:2 in women with a BMI over the median. SM C16:1 and PC ae C30:2 concentrations were positively associated with cholesterol (total and HDL) and inversely associated with number of metabolic syndrome components. Conclusions We identified new biomarkers associated with mammographic density in young women. The association of these biomarkers with mammographic density and metabolic parameters may provide new perspectives to support future preventive actions for breast cancer.
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- 2021
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10. Longitudinal associations of physical activity with plasma metabolites among colorectal cancer survivors up to 2 years after treatment
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Eline H. van Roekel, Martijn J. L. Bours, Linda van Delden, Stéphanie O. Breukink, Michèl Aquarius, Eric T. P. Keulen, Audrey Gicquiau, Vivian Viallon, Sabina Rinaldi, Paolo Vineis, Ilja C. W. Arts, Marc J. Gunter, Michael F. Leitzmann, Augustin Scalbert, and Matty P. Weijenberg
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Medicine ,Science - Abstract
Abstract We investigated longitudinal associations of moderate-to-vigorous physical activity (MVPA) and light-intensity physical activity (LPA) with plasma concentrations of 138 metabolites after colorectal cancer (CRC) treatment. Self-reported physical activity data and blood samples were obtained at 6 weeks, and 6, 12 and 24 months post-treatment in stage I-III CRC survivors (n = 252). Metabolite concentrations were measured by tandem mass spectrometry (BIOCRATES AbsoluteIDQp180 kit). Linear mixed models were used to evaluate confounder-adjusted longitudinal associations. Inter-individual (between-participant differences) and intra-individual associations (within-participant changes over time) were assessed as percentage difference in metabolite concentration per 5 h/week of MVPA or LPA. At 6 weeks post-treatment, participants reported a median of 6.5 h/week of MVPA (interquartile range:2.3,13.5) and 7.5 h/week of LPA (2.0,15.8). Inter-individual associations were observed with more MVPA being related (FDR-adjusted q-value
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- 2021
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11. Association between pre-diagnostic circulating lipid metabolites and colorectal cancer risk:a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC)
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Harewood, Rhea, Rothwell, Joseph A, Bešević, Jelena, Viallon, Vivian, Achaintre, David, Gicquiau, Audrey, Rinaldi, Sabina, Wedekind, Roland, Prehn, Cornelia, Adamski, Jerzy, Schmidt, Julie A, Jacobs, Inarie, Tjønneland, Anne, Olsen, Anja, Severi, Gianluca, Kaaks, Rudolf, Katzke, Verena, Schulze, Matthias B, Prada, Marcela, Masala, Giovanna, Agnoli, Claudia, Panico, Salvatore, Sacerdote, Carlotta, Jakszyn, Paula Gabriela, Sánchez, Maria-Jose, Castilla, Jesús, Chirlaque, María-Dolores, Atxega, Amaia Aizpurua, van Guelpen, Bethany, Heath, Alicia K, Papier, Keren, Tong, Tammy Y N, Summers, Scott A, Playdon, Mary, Cross, Amanda J, Keski-Rahkonen, Pekka, Chajès, Véronique, Murphy, Neil, Gunter, Marc J, Harewood, Rhea, Rothwell, Joseph A, Bešević, Jelena, Viallon, Vivian, Achaintre, David, Gicquiau, Audrey, Rinaldi, Sabina, Wedekind, Roland, Prehn, Cornelia, Adamski, Jerzy, Schmidt, Julie A, Jacobs, Inarie, Tjønneland, Anne, Olsen, Anja, Severi, Gianluca, Kaaks, Rudolf, Katzke, Verena, Schulze, Matthias B, Prada, Marcela, Masala, Giovanna, Agnoli, Claudia, Panico, Salvatore, Sacerdote, Carlotta, Jakszyn, Paula Gabriela, Sánchez, Maria-Jose, Castilla, Jesús, Chirlaque, María-Dolores, Atxega, Amaia Aizpurua, van Guelpen, Bethany, Heath, Alicia K, Papier, Keren, Tong, Tammy Y N, Summers, Scott A, Playdon, Mary, Cross, Amanda J, Keski-Rahkonen, Pekka, Chajès, Véronique, Murphy, Neil, and Gunter, Marc J
- Abstract
Background Altered lipid metabolism is a hallmark of cancer development. However, the role of specific lipid metabolites in colorectal cancer development is uncertain. Methods In a case–control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), we examined associations between pre-diagnostic circulating concentrations of 97 lipid metabolites (acylcarnitines, glycerophospholipids and sphingolipids) and colorectal cancer risk. Circulating lipids were measured using targeted mass spectrometry in 1591 incident colorectal cancer cases (55% women) and 1591 matched controls. Multivariable conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between concentrations of individual lipid metabolites and metabolite patterns with colorectal cancer risk. Findings Of the 97 assayed lipids, 24 were inversely associated (nominally p < 0.05) with colorectal cancer risk. Hydroxysphingomyelin (SM (OH)) C22:2 (ORper doubling 0.60, 95% CI 0.47–0.77) and acylakyl-phosphatidylcholine (PC ae) C34:3 (ORper doubling 0.71, 95% CI 0.59–0.87) remained associated after multiple comparisons correction. These associations were unaltered after excluding the first 5 years of follow-up after blood collection and were consistent according to sex, age at diagnosis, BMI, and colorectal subsite. Two lipid patterns, one including 26 phosphatidylcholines and all sphingolipids, and another 30 phosphatidylcholines, were weakly inversely associated with colorectal cancer. Interpretation Elevated pre-diagnostic circulating levels of SM (OH) C22:2 and PC ae C34:3 and lipid patterns including phosphatidylcholines and sphingolipids were associated with lower colorectal cancer risk. This study may provide insight into potential links between specific lipids and colorectal cancer development. Additional prospective studies are needed to validate the observed ass, BACKGROUND: Altered lipid metabolism is a hallmark of cancer development. However, the role of specific lipid metabolites in colorectal cancer development is uncertain.METHODS: In a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), we examined associations between pre-diagnostic circulating concentrations of 97 lipid metabolites (acylcarnitines, glycerophospholipids and sphingolipids) and colorectal cancer risk. Circulating lipids were measured using targeted mass spectrometry in 1591 incident colorectal cancer cases (55% women) and 1591 matched controls. Multivariable conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between concentrations of individual lipid metabolites and metabolite patterns with colorectal cancer risk.FINDINGS: Of the 97 assayed lipids, 24 were inversely associated (nominally p < 0.05) with colorectal cancer risk. Hydroxysphingomyelin (SM (OH)) C22:2 (ORper doubling 0.60, 95% CI 0.47-0.77) and acylakyl-phosphatidylcholine (PC ae) C34:3 (ORper doubling 0.71, 95% CI 0.59-0.87) remained associated after multiple comparisons correction. These associations were unaltered after excluding the first 5 years of follow-up after blood collection and were consistent according to sex, age at diagnosis, BMI, and colorectal subsite. Two lipid patterns, one including 26 phosphatidylcholines and all sphingolipids, and another 30 phosphatidylcholines, were weakly inversely associated with colorectal cancer.INTERPRETATION: Elevated pre-diagnostic circulating levels of SM (OH) C22:2 and PC ae C34:3 and lipid patterns including phosphatidylcholines and sphingolipids were associated with lower colorectal cancer risk. This study may provide insight into potential links between specific lipids and colorectal cancer development. Additional prospective studies are needed to validate the observed associations.F
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- 2024
12. Metabolic signatures of greater body size and their associations with risk of colorectal and endometrial cancers in the European Prospective Investigation into Cancer and Nutrition
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Nathalie Kliemann, Vivian Viallon, Neil Murphy, Rebecca J. Beeken, Joseph A. Rothwell, Sabina Rinaldi, Nada Assi, Eline H. van Roekel, Julie A. Schmidt, Kristin Benjaminsen Borch, Claudia Agnoli, Ann H. Rosendahl, Hanna Sartor, José María Huerta, Anne Tjønneland, Jytte Halkjær, Bas Bueno-de-Mesquita, Audrey Gicquiau, David Achaintre, Krasimira Aleksandrova, Matthias B. Schulze, Alicia K. Heath, Konstantinos K. Tsilidis, Giovanna Masala, Salvatore Panico, Rudolf Kaaks, Renée T. Fortner, Bethany Van Guelpen, Laure Dossus, Augustin Scalbert, Hector C. Keun, Ruth C. Travis, Mazda Jenab, Mattias Johansson, Pietro Ferrari, and Marc J. Gunter
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Metabolomics ,Obesity ,Weight loss ,Cancer ,Medicine - Abstract
Abstract Background The mechanisms underlying the obesity-cancer relationship are incompletely understood. This study aimed to characterise metabolic signatures of greater body size and to investigate their association with two obesity-related malignancies, endometrial and colorectal cancers, and with weight loss within the context of an intervention study. Methods Targeted mass spectrometry metabolomics data from 4326 participants enrolled in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort and 17 individuals from a single-arm pilot weight loss intervention (Intercept) were used in this analysis. Metabolic signatures of body size were first determined in discovery (N = 3029) and replication (N = 1297) sets among EPIC participants by testing the associations between 129 metabolites and body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) using linear regression models followed by partial least squares analyses. Conditional logistic regression models assessed the associations between the metabolic signatures with endometrial (N = 635 cases and 648 controls) and colorectal (N = 423 cases and 423 controls) cancer risk using nested case-control studies in EPIC. Pearson correlation between changes in the metabolic signatures and weight loss was tested among Intercept participants. Results After adjustment for multiple comparisons, greater BMI, WC, and WHR were associated with higher levels of valine, isoleucine, glutamate, PC aa C38:3, and PC aa C38:4 and with lower levels of asparagine, glutamine, glycine, serine, lysoPC C17:0, lysoPC C18:1, lysoPC C18:2, PC aa C42:0, PC ae C34:3, PC ae C40:5, and PC ae C42:5. The metabolic signature of BMI (OR1-sd 1.50, 95% CI 1.30–1.74), WC (OR1-sd 1.46, 95% CI 1.27–1.69), and WHR (OR1-sd 1.54, 95% CI 1.33–1.79) were each associated with endometrial cancer risk. Risk of colorectal cancer was positively associated with the metabolic signature of WHR (OR1-sd: 1.26, 95% CI 1.07–1.49). In the Intercept study, a positive correlation was observed between weight loss and changes in the metabolic signatures of BMI (r = 0.5, 95% CI 0.06–0.94, p = 0.03), WC (r = 0.5, 95% CI 0.05–0.94, p = 0.03), and WHR (r = 0.6, 95% CI 0.32–0.87, p = 0.01). Conclusions Obesity is associated with a distinct metabolic signature comprising changes in levels of specific amino acids and lipids which is positively associated with both colorectal and endometrial cancer and is potentially reversible following weight loss.
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- 2021
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13. Head-and-Neck MRI-only radiotherapy treatment planning: From acquisition in treatment position to pseudo-CT generation
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Largent, A., Marage, L., Gicquiau, I., Nunes, J.-C., Reynaert, N., Castelli, J., Chajon, E., Acosta, O., Gambarota, G., de Crevoisier, R., and Saint-Jalmes, H.
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- 2020
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14. Longitudinal associations of physical activity with plasma metabolites among colorectal cancer survivors up to 2 years after treatment
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van Roekel, Eline H., Bours, Martijn J. L., van Delden, Linda, Breukink, Stéphanie O., Aquarius, Michèl, Keulen, Eric T. P., Gicquiau, Audrey, Viallon, Vivian, Rinaldi, Sabina, Vineis, Paolo, Arts, Ilja C. W., Gunter, Marc J., Leitzmann, Michael F., Scalbert, Augustin, and Weijenberg, Matty P.
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- 2021
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15. Metabolic signatures of greater body size and their associations with risk of colorectal and endometrial cancers in the European Prospective Investigation into Cancer and Nutrition
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Kliemann, Nathalie, Viallon, Vivian, Murphy, Neil, Beeken, Rebecca J., Rothwell, Joseph A., Rinaldi, Sabina, Assi, Nada, van Roekel, Eline H., Schmidt, Julie A., Borch, Kristin Benjaminsen, Agnoli, Claudia, Rosendahl, Ann H., Sartor, Hanna, Huerta, José María, Tjønneland, Anne, Halkjær, Jytte, Bueno-de-Mesquita, Bas, Gicquiau, Audrey, Achaintre, David, Aleksandrova, Krasimira, Schulze, Matthias B., Heath, Alicia K., Tsilidis, Konstantinos K., Masala, Giovanna, Panico, Salvatore, Kaaks, Rudolf, Fortner, Renée T., Van Guelpen, Bethany, Dossus, Laure, Scalbert, Augustin, Keun, Hector C., Travis, Ruth C., Jenab, Mazda, Johansson, Mattias, Ferrari, Pietro, and Gunter, Marc J.
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- 2021
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16. Biomarkers of mammographic density in premenopausal women
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His, Mathilde, Lajous, Martin, Gómez-Flores-Ramos, Liliana, Monge, Adriana, Dossus, Laure, Viallon, Vivian, Gicquiau, Audrey, Biessy, Carine, Gunter, Marc J., and Rinaldi, Sabina
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- 2021
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17. The blood metabolome of incident kidney cancer: A case-control study nested within the MetKid consortium.
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Florence Guida, Vanessa Y Tan, Laura J Corbin, Karl Smith-Byrne, Karine Alcala, Claudia Langenberg, Isobel D Stewart, Adam S Butterworth, Praveen Surendran, David Achaintre, Jerzy Adamski, Pilar Amiano, Manuela M Bergmann, Caroline J Bull, Christina C Dahm, Audrey Gicquiau, Graham G Giles, Marc J Gunter, Toomas Haller, Arnulf Langhammer, Tricia L Larose, Börje Ljungberg, Andres Metspalu, Roger L Milne, David C Muller, Therese H Nøst, Elin Pettersen Sørgjerd, Cornelia Prehn, Elio Riboli, Sabina Rinaldi, Joseph A Rothwell, Augustin Scalbert, Julie A Schmidt, Gianluca Severi, Sabina Sieri, Roel Vermeulen, Emma E Vincent, Melanie Waldenberger, Nicholas J Timpson, and Mattias Johansson
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Medicine - Abstract
BackgroundExcess bodyweight and related metabolic perturbations have been implicated in kidney cancer aetiology, but the specific molecular mechanisms underlying these relationships are poorly understood. In this study, we sought to identify circulating metabolites that predispose kidney cancer and to evaluate the extent to which they are influenced by body mass index (BMI).Methods and findingsWe assessed the association between circulating levels of 1,416 metabolites and incident kidney cancer using pre-diagnostic blood samples from up to 1,305 kidney cancer case-control pairs from 5 prospective cohort studies. Cases were diagnosed on average 8 years after blood collection. We found 25 metabolites robustly associated with kidney cancer risk. In particular, 14 glycerophospholipids (GPLs) were inversely associated with risk, including 8 phosphatidylcholines (PCs) and 2 plasmalogens. The PC with the strongest association was PC ae C34:3 with an odds ratio (OR) for 1 standard deviation (SD) increment of 0.75 (95% confidence interval [CI]: 0.68 to 0.83, p = 2.6 × 10-8). In contrast, 4 amino acids, including glutamate (OR for 1 SD = 1.39, 95% CI: 1.20 to 1.60, p = 1.6 × 10-5), were positively associated with risk. Adjusting for BMI partly attenuated the risk association for some-but not all-metabolites, whereas other known risk factors of kidney cancer, such as smoking and alcohol consumption, had minimal impact on the observed associations. A mendelian randomisation (MR) analysis of the influence of BMI on the blood metabolome highlighted that some metabolites associated with kidney cancer risk are influenced by BMI. Specifically, elevated BMI appeared to decrease levels of several GPLs that were also found inversely associated with kidney cancer risk (e.g., -0.17 SD change [ßBMI] in 1-(1-enyl-palmitoyl)-2-linoleoyl-GPC (P-16:0/18:2) levels per SD change in BMI, p = 3.4 × 10-5). BMI was also associated with increased levels of glutamate (ßBMI: 0.12, p = 1.5 × 10-3). While our results were robust across the participating studies, they were limited to study participants of European descent, and it will, therefore, be important to evaluate if our findings can be generalised to populations with different genetic backgrounds.ConclusionsThis study suggests a potentially important role of the blood metabolome in kidney cancer aetiology by highlighting a wide range of metabolites associated with the risk of developing kidney cancer and the extent to which changes in levels of these metabolites are driven by BMI-the principal modifiable risk factor of kidney cancer.
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- 2021
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18. Prospective analysis of circulating metabolites and breast cancer in EPIC
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Mathilde His, Vivian Viallon, Laure Dossus, Audrey Gicquiau, David Achaintre, Augustin Scalbert, Pietro Ferrari, Isabelle Romieu, N. Charlotte Onland-Moret, Elisabete Weiderpass, Christina C. Dahm, Kim Overvad, Anja Olsen, Anne Tjønneland, Agnès Fournier, Joseph A. Rothwell, Gianluca Severi, Tilman Kühn, Renée T. Fortner, Heiner Boeing, Antonia Trichopoulou, Anna Karakatsani, Georgia Martimianaki, Giovanna Masala, Sabina Sieri, Rosario Tumino, Paolo Vineis, Salvatore Panico, Carla H. van Gils, Therese H. Nøst, Torkjel M. Sandanger, Guri Skeie, J. Ramón Quirós, Antonio Agudo, Maria-Jose Sánchez, Pilar Amiano, José María Huerta, Eva Ardanaz, Julie A. Schmidt, Ruth C. Travis, Elio Riboli, Konstantinos K. Tsilidis, Sofia Christakoudi, Marc J. Gunter, and Sabina Rinaldi
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Breast cancer ,Metabolomics ,Prospective study ,Medicine - Abstract
Abstract Background Metabolomics is a promising molecular tool to identify novel etiologic pathways leading to cancer. Using a targeted approach, we prospectively investigated the associations between metabolite concentrations in plasma and breast cancer risk. Methods A nested case-control study was established within the European Prospective Investigation into Cancer cohort, which included 1624 first primary incident invasive breast cancer cases (with known estrogen and progesterone receptor and HER2 status) and 1624 matched controls. Metabolites (n = 127, acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexose, sphingolipids) were measured by mass spectrometry in pre-diagnostic plasma samples and tested for associations with breast cancer incidence using multivariable conditional logistic regression. Results Among women not using hormones at baseline (n = 2248), and after control for multiple tests, concentrations of arginine (odds ratio [OR] per SD = 0.79, 95% confidence interval [CI] = 0.70–0.90), asparagine (OR = 0.83 (0.74–0.92)), and phosphatidylcholines (PCs) ae C36:3 (OR = 0.83 (0.76–0.90)), aa C36:3 (OR = 0.84 (0.77–0.93)), ae C34:2 (OR = 0.85 (0.78–0.94)), ae C36:2 (OR = 0.85 (0.78–0.88)), and ae C38:2 (OR = 0.84 (0.76–0.93)) were inversely associated with breast cancer risk, while the acylcarnitine C2 (OR = 1.23 (1.11–1.35)) was positively associated with disease risk. In the overall population, C2 (OR = 1.15 (1.06–1.24)) and PC ae C36:3 (OR = 0.88 (0.82–0.95)) were associated with risk of breast cancer, and these relationships did not differ by breast cancer subtype, age at diagnosis, fasting status, menopausal status, or adiposity. Conclusions These findings point to potentially novel pathways and biomarkers of breast cancer development. Results warrant replication in other epidemiological studies.
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- 2019
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19. Quantification of 38 dietary polyphenols in plasma by differential isotope labelling and liquid chromatography electrospray ionization tandem mass spectrometry
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Achaintre, David, Gicquiau, Audrey, Li, Liang, Rinaldi, Sabina, and Scalbert, Augustin
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- 2018
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20. Higher Plasma Creatinine Is Associated with an Increased Risk of Death in Patients with Non-Metastatic Rectal but Not Colon Cancer: Results from an International Cohort Consortium
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Ose, Jennifer, primary, Gigic, Biljana, additional, Brezina, Stefanie, additional, Lin, Tengda, additional, Peoples, Anita R., additional, Schobert, Pauline P., additional, Baierl, Andreas, additional, van Roekel, Eline, additional, Robinot, Nivonirina, additional, Gicquiau, Audrey, additional, Achaintre, David, additional, Scalbert, Augustin, additional, van Duijnhoven, Fränzel J. B., additional, Holowatyj, Andreana N., additional, Gumpenberger, Tanja, additional, Schrotz-King, Petra, additional, Ulrich, Alexis B., additional, Ulvik, Arve, additional, Ueland, Per-Magne, additional, Weijenberg, Matty P., additional, Habermann, Nina, additional, Keski-Rahkonen, Pekka, additional, Gsur, Andrea, additional, Kok, Dieuwertje E., additional, and Ulrich, Cornelia M., additional
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- 2023
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21. The blood metabolome of incident kidney cancer: A case-control study nested within the MetKid consortium
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Guida, Florence, Tan, Vanessa Y., Corbin, Laura J., Smith-Byrne, Karl, Alcala, Karine, Langenberg, Claudia, Stewart, Isobel D., Butterworth, Adam S., Surendran, Praveen, Achaintre, David, Adamski, Jerzy, Amiano Exezarreta, Pilar, Bergmann, Manuela M., Bull, Caroline J., Dahm, Christina C., Gicquiau, Audrey, Giles, Graham G., Gunter, Marc J., Haller, Toomas, Langhammer, Arnulf, Larose, Tricia L., Ljungberg, Börje, Metspalu, Andres, Milne, Roger L., Muller, David C., Nøst, Therese H., Pettersen Sørgjerd, Elin, Prehn, Cornelia, Riboli, Elio, Rinaldi, Sabina, Rothwell, Joseph A., Scalbert, Augustin, Schmidt, Julie A., Severi, Gianluca, Sieri, Sabina, Vermeulen, Roel, Vincent, Emma E., Waldenberger, Melanie, Timpson, Nicholas J., and Johansson, Mattias
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Kidney cancer -- Risk factors -- Development and progression -- Physiological aspects ,Metabolites -- Health aspects -- Measurement ,Body mass index ,Biological sciences - Abstract
Background Excess bodyweight and related metabolic perturbations have been implicated in kidney cancer aetiology, but the specific molecular mechanisms underlying these relationships are poorly understood. In this study, we sought to identify circulating metabolites that predispose kidney cancer and to evaluate the extent to which they are influenced by body mass index (BMI). Methods and findings We assessed the association between circulating levels of 1,416 metabolites and incident kidney cancer using pre-diagnostic blood samples from up to 1,305 kidney cancer case-control pairs from 5 prospective cohort studies. Cases were diagnosed on average 8 years after blood collection. We found 25 metabolites robustly associated with kidney cancer risk. In particular, 14 glycerophospholipids (GPLs) were inversely associated with risk, including 8 phosphatidylcholines (PCs) and 2 plasmalogens. The PC with the strongest association was PC ae C34:3 with an odds ratio (OR) for 1 standard deviation (SD) increment of 0.75 (95% confidence interval [CI]: 0.68 to 0.83, p = 2.6 x 10.sup.-8). In contrast, 4 amino acids, including glutamate (OR for 1 SD = 1.39, 95% CI: 1.20 to 1.60, p = 1.6 x 10.sup.-5 ), were positively associated with risk. Adjusting for BMI partly attenuated the risk association for some-but not all-metabolites, whereas other known risk factors of kidney cancer, such as smoking and alcohol consumption, had minimal impact on the observed associations. A mendelian randomisation (MR) analysis of the influence of BMI on the blood metabolome highlighted that some metabolites associated with kidney cancer risk are influenced by BMI. Specifically, elevated BMI appeared to decrease levels of several GPLs that were also found inversely associated with kidney cancer risk (e.g., -0.17 SD change [ß.sub.BMI ] in 1-(1-enyl-palmitoyl)-2-linoleoyl-GPC (P-16:0/18:2) levels per SD change in BMI, p = 3.4 x 10.sup.-5). BMI was also associated with increased levels of glutamate (ß.sub.BMI : 0.12, p = 1.5 x 10.sup.-3). While our results were robust across the participating studies, they were limited to study participants of European descent, and it will, therefore, be important to evaluate if our findings can be generalised to populations with different genetic backgrounds. Conclusions This study suggests a potentially important role of the blood metabolome in kidney cancer aetiology by highlighting a wide range of metabolites associated with the risk of developing kidney cancer and the extent to which changes in levels of these metabolites are driven by BMI-the principal modifiable risk factor of kidney cancer., Author(s): Florence Guida 1, Vanessa Y. Tan 2,3, Laura J. Corbin 2,3, Karl Smith-Byrne 1, Karine Alcala 1, Claudia Langenberg 4, Isobel D. Stewart 4, Adam S. Butterworth 5,6,7,8, Praveen [...]
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- 2021
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22. A New Pipeline for the Normalization and Pooling of Metabolomics Data
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Vivian Viallon, Mathilde His, Sabina Rinaldi, Marie Breeur, Audrey Gicquiau, Bertrand Hemon, Kim Overvad, Anne Tjønneland, Agnetha Linn Rostgaard-Hansen, Joseph A. Rothwell, Lucie Lecuyer, Gianluca Severi, Rudolf Kaaks, Theron Johnson, Matthias B. Schulze, Domenico Palli, Claudia Agnoli, Salvatore Panico, Rosario Tumino, Fulvio Ricceri, W. M. Monique Verschuren, Peter Engelfriet, Charlotte Onland-Moret, Roel Vermeulen, Therese Haugdahl Nøst, Ilona Urbarova, Raul Zamora-Ros, Miguel Rodriguez-Barranco, Pilar Amiano, José Maria Huerta, Eva Ardanaz, Olle Melander, Filip Ottoson, Linda Vidman, Matilda Rentoft, Julie A. Schmidt, Ruth C. Travis, Elisabete Weiderpass, Mattias Johansson, Laure Dossus, Mazda Jenab, Marc J. Gunter, Justo Lorenzo Bermejo, Dominique Scherer, Reza M. Salek, Pekka Keski-Rahkonen, and Pietro Ferrari
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cancer epidemiology ,normalization ,pooling ,technical variability ,metabolomics ,metabolites ,Microbiology ,QR1-502 - 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.
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- 2021
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23. Higher Plasma Creatinine Is Associated with an Increased Risk of Death in Patients with Non-Metastatic Rectal but Not Colon Cancer: Results from an International Cohort Consortium
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Ulrich, Jennifer Ose, Biljana Gigic, Stefanie Brezina, Tengda Lin, Anita R. Peoples, Pauline P. Schobert, Andreas Baierl, Eline van Roekel, Nivonirina Robinot, Audrey Gicquiau, David Achaintre, Augustin Scalbert, Fränzel J. B. van Duijnhoven, Andreana N. Holowatyj, Tanja Gumpenberger, Petra Schrotz-King, Alexis B. Ulrich, Arve Ulvik, Per-Magne Ueland, Matty P. Weijenberg, Nina Habermann, Pekka Keski-Rahkonen, Andrea Gsur, Dieuwertje E. Kok, and Cornelia M.
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all-cause mortality ,creatinine ,metabolites ,colon cancer ,rectal cancer ,starch and sucrose pathway - Abstract
Colorectal cancer (CRC) is increasingly recognized as a heterogeneous disease. No studies have prospectively examined associations of blood metabolite concentrations with all-cause mortality in patients with colon and rectal cancer separately. Targeted metabolomics (Biocrates AbsoluteIDQ p180) and pathway analyses (MetaboAnalyst 4.0) were performed on pre-surgery collected plasma from 674 patients with non-metastasized (stage I–III) colon (n = 394) or rectal cancer (n = 283). Metabolomics data and covariate information were received from the international cohort consortium MetaboCCC. Cox proportional hazards models were computed to investigate associations of 148 metabolite levels with all-cause mortality adjusted for age, sex, tumor stage, tumor site (whenever applicable), and cohort; the false discovery rate (FDR) was used to account for multiple testing. A total of 93 patients (14%) were deceased after an average follow-up time of 4.4 years (60 patients with colon cancer and 33 patients with rectal cancer). After FDR adjustment, higher plasma creatinine was associated with a 39% increase in all-cause mortality in patients with rectal cancer. HR: 1.39, 95% CI 1.23–1.72, pFDR = 0.03; but not colon cancer: pFDR = 0.96. Creatinine is a breakdown product of creatine phosphate in muscle and may reflect changes in skeletal muscle mass. The starch and sucrose metabolisms were associated with increased all-cause mortality in colon cancer but not in rectal cancer. Genes in the starch and sucrose metabolism pathways were previously linked to worse clinical outcomes in CRC. In summary, our findings support the hypothesis that colon and rectal cancer have different etiological and clinical outcomes that need to be considered for targeted treatments.
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- 2023
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24. Pre-diagnostic metabolite concentrations and prostate cancer risk in 1077 cases and 1077 matched controls in the European Prospective Investigation into Cancer and Nutrition
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Julie A. Schmidt, Georgina K. Fensom, Sabina Rinaldi, Augustin Scalbert, Paul N. Appleby, David Achaintre, Audrey Gicquiau, Marc J. Gunter, Pietro Ferrari, Rudolf Kaaks, Tilman Kühn, Anna Floegel, Heiner Boeing, Antonia Trichopoulou, Pagona Lagiou, Eleutherios Anifantis, Claudia Agnoli, Domenico Palli, Morena Trevisan, Rosario Tumino, H. Bas Bueno-de-Mesquita, Antonio Agudo, Nerea Larrañaga, Daniel Redondo-Sánchez, Aurelio Barricarte, José Maria Huerta, J. Ramón Quirós, Nick Wareham, Kay-Tee Khaw, Aurora Perez-Cornago, Mattias Johansson, Amanda J. Cross, Konstantinos K. Tsilidis, Elio Riboli, Timothy J. Key, and Ruth C. Travis
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Acylcarnitines ,Amino acids ,Biogenic amines ,European Prospective Investigation into Cancer and Nutrition (EPIC) ,Glycerophospholipids ,Hexose ,Medicine - Abstract
Abstract Background Little is known about how pre-diagnostic metabolites in blood relate to risk of prostate cancer. We aimed to investigate the prospective association between plasma metabolite concentrations and risk of prostate cancer overall, and by time to diagnosis and tumour characteristics, and risk of death from prostate cancer. Methods In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition, pre-diagnostic plasma concentrations of 122 metabolites (including acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexose and sphingolipids) were measured using targeted mass spectrometry (AbsoluteIDQ p180 Kit) and compared between 1077 prostate cancer cases and 1077 matched controls. Risk of prostate cancer associated with metabolite concentrations was estimated by multi-variable conditional logistic regression, and multiple testing was accounted for by using a false discovery rate controlling procedure. Results Seven metabolite concentrations, i.e. acylcarnitine C18:1, amino acids citrulline and trans-4-hydroxyproline, glycerophospholipids PC aa C28:1, PC ae C30:0 and PC ae C30:2, and sphingolipid SM (OH) C14:1, were associated with prostate cancer (p
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- 2017
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25. Higher Plasma Creatinine Is Associated with an Increased Risk of Death in Patients with Non-Metastatic Rectal but Not Colon Cancer : Results from an International Cohort Consortium
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Ose, Jennifer, Gigic, Biljana, Brezina, Stefanie, Lin, Tengda, Peoples, Anita R., Schobert, Pauline P., Baierl, Andreas, van Roekel, Eline, Robinot, Nivonirina, Gicquiau, Audrey, Achaintre, David, Scalbert, Augustin, van Duijnhoven, Fränzel J.B., Holowatyj, Andreana N., Gumpenberger, Tanja, Schrotz-King, Petra, Ulrich, Alexis B., Ulvik, Arve, Ueland, Per Magne, Weijenberg, Matty P., Habermann, Nina, Keski-Rahkonen, Pekka, Gsur, Andrea, Kok, Dieuwertje E., Ulrich, Cornelia M., Ose, Jennifer, Gigic, Biljana, Brezina, Stefanie, Lin, Tengda, Peoples, Anita R., Schobert, Pauline P., Baierl, Andreas, van Roekel, Eline, Robinot, Nivonirina, Gicquiau, Audrey, Achaintre, David, Scalbert, Augustin, van Duijnhoven, Fränzel J.B., Holowatyj, Andreana N., Gumpenberger, Tanja, Schrotz-King, Petra, Ulrich, Alexis B., Ulvik, Arve, Ueland, Per Magne, Weijenberg, Matty P., Habermann, Nina, Keski-Rahkonen, Pekka, Gsur, Andrea, Kok, Dieuwertje E., and Ulrich, Cornelia M.
- Abstract
Colorectal cancer (CRC) is increasingly recognized as a heterogeneous disease. No studies have prospectively examined associations of blood metabolite concentrations with all-cause mortality in patients with colon and rectal cancer separately. Targeted metabolomics (Biocrates AbsoluteIDQ p180) and pathway analyses (MetaboAnalyst 4.0) were performed on pre-surgery collected plasma from 674 patients with non-metastasized (stage I–III) colon (n = 394) or rectal cancer (n = 283). Metabolomics data and covariate information were received from the international cohort consortium MetaboCCC. Cox proportional hazards models were computed to investigate associations of 148 metabolite levels with all-cause mortality adjusted for age, sex, tumor stage, tumor site (whenever applicable), and cohort; the false discovery rate (FDR) was used to account for multiple testing. A total of 93 patients (14%) were deceased after an average follow-up time of 4.4 years (60 patients with colon cancer and 33 patients with rectal cancer). After FDR adjustment, higher plasma creatinine was associated with a 39% increase in all-cause mortality in patients with rectal cancer. HR: 1.39, 95% CI 1.23–1.72, pFDR = 0.03; but not colon cancer: pFDR = 0.96. Creatinine is a breakdown product of creatine phosphate in muscle and may reflect changes in skeletal muscle mass. The starch and sucrose metabolisms were associated with increased all-cause mortality in colon cancer but not in rectal cancer. Genes in the starch and sucrose metabolism pathways were previously linked to worse clinical outcomes in CRC. In summary, our findings support the hypothesis that colon and rectal cancer have different etiological and clinical outcomes that need to be considered for targeted treatments.
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- 2023
26. Circulating amino acid levels and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition and UK Biobank cohorts
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Epi Kanker Team B, Cancer, MS MDL 1, Rothwell, Joseph A, Bešević, Jelena, Dimou, Niki, Breeur, Marie, Murphy, Neil, Jenab, Mazda, Wedekind, Roland, Viallon, Vivian, Ferrari, Pietro, Achaintre, David, Gicquiau, Audrey, Rinaldi, Sabina, Scalbert, Augustin, Huybrechts, Inge, Prehn, Cornelia, Adamski, Jerzy, Cross, Amanda J, Keun, Hector, Chadeau-Hyam, Marc, Boutron-Ruault, Marie-Christine, Overvad, Kim, Dahm, Christina C, Nøst, Therese Haugdahl, Sandanger, Torkjel M, Skeie, Guri, Zamora-Ros, Raul, Tsilidis, Kostas K, Eichelmann, Fabian, Schulze, Matthias B, van Guelpen, Bethany, Vidman, Linda, Sánchez, Maria-José, Amiano, Pilar, Ardanaz, Eva, Smith-Byrne, Karl, Travis, Ruth, Katzke, Verena, Kaaks, Rudolf, Derksen, Jeroen W G, Colorado-Yohar, Sandra, Tumino, Rosario, Bueno-de-Mesquita, Bas, Vineis, Paolo, Palli, Domenico, Pasanisi, Fabrizio, Eriksen, Anne Kirstine, Tjønneland, Anne, Severi, Gianluca, Gunter, Marc J, Epi Kanker Team B, Cancer, MS MDL 1, Rothwell, Joseph A, Bešević, Jelena, Dimou, Niki, Breeur, Marie, Murphy, Neil, Jenab, Mazda, Wedekind, Roland, Viallon, Vivian, Ferrari, Pietro, Achaintre, David, Gicquiau, Audrey, Rinaldi, Sabina, Scalbert, Augustin, Huybrechts, Inge, Prehn, Cornelia, Adamski, Jerzy, Cross, Amanda J, Keun, Hector, Chadeau-Hyam, Marc, Boutron-Ruault, Marie-Christine, Overvad, Kim, Dahm, Christina C, Nøst, Therese Haugdahl, Sandanger, Torkjel M, Skeie, Guri, Zamora-Ros, Raul, Tsilidis, Kostas K, Eichelmann, Fabian, Schulze, Matthias B, van Guelpen, Bethany, Vidman, Linda, Sánchez, Maria-José, Amiano, Pilar, Ardanaz, Eva, Smith-Byrne, Karl, Travis, Ruth, Katzke, Verena, Kaaks, Rudolf, Derksen, Jeroen W G, Colorado-Yohar, Sandra, Tumino, Rosario, Bueno-de-Mesquita, Bas, Vineis, Paolo, Palli, Domenico, Pasanisi, Fabrizio, Eriksen, Anne Kirstine, Tjønneland, Anne, Severi, Gianluca, and Gunter, Marc J
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- 2023
27. Targeted Plasma Metabolic Profiles and Risk of Recurrence in Stage II and III Colorectal Cancer Patients: Results from an International Cohort Consortium
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Jennifer Ose, Biljana Gigic, Stefanie Brezina, Tengda Lin, Andreas Baierl, Anne J. M. R. Geijsen, Eline van Roekel, Nivonirina Robinot, Audrey Gicquiau, David Achaintre, Pekka Keski-Rahkonen, Fränzel J. B. van Duijnhoven, Tanja Gumpenberger, Andreana N. Holowatyj, Dieuwertje E. Kok, Annaleen Koole, Petra Schrotz-King, Alexis B. Ulrich, Martin Schneider, Arve Ulvik, Per-Magne Ueland, Matty P. Weijenberg, Nina Habermann, Augustin Scalbert, Andrea Gsur, and Cornelia M. Ulrich
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colorectal cancer ,recurrence ,targeted metabolomics ,Microbiology ,QR1-502 - Abstract
The identification of patients at high-risk for colorectal cancer (CRC) recurrence remains an unmet clinical need. The aim of this study was to investigate associations of metabolites with risk of recurrence in stage II/III CRC patients. A targeted metabolomics assay (128 metabolites measured) was performed on pre-surgery collected EDTA plasma samples from n = 440 newly diagnosed stage II/III CRC patients. Patients have been recruited from four prospective cohort studies as part of an international consortium: Metabolomic profiles throughout the continuum of CRC (MetaboCCC). Cox proportional hazard models were computed to investigate associations of metabolites with recurrence, adjusted for age, sex, tumor stage, tumor site, body mass index, and cohort; false discovery rate (FDR) was used to account for multiple testing. Sixty-nine patients (15%) had a recurrence after a median follow-up time of 20 months. We identified 13 metabolites that were nominally associated with a reduced risk of recurrence. None of the associations were statistically significant after controlling for multiple testing. Pathway topology analyses did not reveal statistically significant associations between recurrence and alterations in metabolic pathways (e.g., sphingolipid metabolism p = 0.04; pFDR = 1.00). To conclude, we did not observe statistically significant associations between metabolites and CRC recurrence using a well-established metabolomics assay. The observed results require follow-up in larger studies.
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- 2021
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28. Prospective analysis of circulating metabolites and breast cancer in EPIC
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His, Mathilde, Viallon, Vivian, Dossus, Laure, Gicquiau, Audrey, Achaintre, David, Scalbert, Augustin, Ferrari, Pietro, Romieu, Isabelle, Onland-Moret, N. Charlotte, Weiderpass, Elisabete, Dahm, Christina C., Overvad, Kim, Olsen, Anja, Tjønneland, Anne, Fournier, Agnès, Rothwell, Joseph A., Severi, Gianluca, Kühn, Tilman, Fortner, Renée T., Boeing, Heiner, Trichopoulou, Antonia, Karakatsani, Anna, Martimianaki, Georgia, Masala, Giovanna, Sieri, Sabina, Tumino, Rosario, Vineis, Paolo, Panico, Salvatore, van Gils, Carla H., Nøst, Therese H., Sandanger, Torkjel M., Skeie, Guri, Quirós, J. Ramón, Agudo, Antonio, Sánchez, Maria-Jose, Amiano, Pilar, Huerta, José María, Ardanaz, Eva, Schmidt, Julie A., Travis, Ruth C., Riboli, Elio, Tsilidis, Konstantinos K., Christakoudi, Sofia, Gunter, Marc J., and Rinaldi, Sabina
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- 2019
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29. Longitudinal associations of plasma metabolites with persistent fatigue among colorectal cancer survivors up to 2 years after treatment
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Eline H. van Roekel, Martijn J. L. Bours, Stéphanie O. Breukink, Michèl Aquarius, Eric T. P. Keulen, Audrey Gicquiau, Sabina Rinaldi, Paolo Vineis, Ilja C. W. Arts, Marc J. Gunter, Michael F. Leitzmann, Augustin Scalbert, Matty P. Weijenberg, Epidemiologie, RS: GROW - R1 - Prevention, Surgery, MUMC+: MA Heelkunde (9), RS: NUTRIM - R2 - Liver and digestive health, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Maastricht Centre for Systems Biology, and RS: FSE MaCSBio
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Cancer Research ,Plasma ,Oncology ,Cancer Survivors ,Humans ,Survivors ,Colorectal Neoplasms ,Fatigue - Abstract
The underlying biological mechanisms causing persistent fatigue complaints after colorectal cancer treatment need further investigation. We investigated longitudinal associations of circulating concentrations of 138 metabolites with total fatigue and subdomains of fatigue between 6 weeks and 2 years after colorectal cancer treatment. Among stage I-III colorectal cancer survivors (n = 252), blood samples were obtained at 6 weeks, and 6, 12 and 24 months posttreatment. Total fatigue and fatigue subdomains were measured using a validated questionnaire. Tandem mass spectrometry was applied to measure metabolite concentrations (BIOCRATES AbsoluteIDQp180 kit). Confounder-adjusted longitudinal associations were analyzed using linear mixed models, with false discovery rate (FDR) correction. We assessed interindividual (between-participant differences) and intraindividual longitudinal associations (within-participant changes over time). In the overall longitudinal analysis, statistically significant associations were observed for 12, 32, 17 and three metabolites with total fatigue and the subscales "fatigue severity," "reduced motivation" and "reduced activity," respectively. Specifically, higher concentrations of several amino acids, lysophosphatidylcholines, diacylphosphatidylcholines, acyl-alkylphosphatidylcholines and sphingomyelins were associated with less fatigue, while higher concentrations of acylcarnitines were associated with more fatigue. For "fatigue severity," associations appeared mainly driven by intraindividual associations, while for "reduced motivation" stronger interindividual associations were found. We observed longitudinal associations of several metabolites with total fatigue and fatigue subscales, and that intraindividual changes in metabolites over time were associated with fatigue severity. These findings point toward inflammation and an impaired energy metabolism due to mitochondrial dysfunction as underlying mechanisms. Mechanistic studies are necessary to determine whether these metabolites could be targets for intervention.
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- 2023
30. Circulating tryptophan metabolites and risk of colon cancer: Results from case-control and prospective cohort studies
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David Achaintre, Pekka Keski-Rahkonen, Matty P. Weijenberg, Verena Katzke, Nikos Papadimitriou, Ellen Kampman, Augustin Scalbert, Audrey Gicquiau, Sandra Colorado-Yohar, Neil Murphy, Per Magne Ueland, Ruth C. Travis, Jennifer Ose, Anne J.M.R. Geijsen, Elisabete Weiderpass, María José Sánchez, Andrea Gsur, Andreas Baierl, Marc J. Gunter, Cornelia M. Ulrich, Biljana Gigic, Eva Ardanaz, Vittorio Krogh, Bas Bueno-de-Mesquita, Stefanie Brezina, Eline H. van Roekel, Tanja Gumpenberger, Nina Habermann, Rudolf Kaaks, Matthias B. Schulze, RS: GROW - R1 - Prevention, and Epidemiologie
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Male ,Cancer Research ,Nutrition and Disease ,Colorectal cancer ,Gastroenterology ,DISEASE ,COLORECTAL-CANCER ,IDO ,chemistry.chemical_compound ,MARKERS ,Risk Factors ,ADIPONECTIN ,Voeding en Ziekte ,Epidemiology ,Prospective Studies ,Prospective cohort study ,Aged, 80 and over ,Middle Aged ,INSULIN ,European Prospective Investigation into Cancer and Nutrition ,serotonin ,Oncology ,colon cancer ,Colonic Neoplasms ,Female ,Adult ,medicine.medical_specialty ,Article ,INFLAMMATION ,Internal medicine ,medicine ,Humans ,tryptophan ,plasma ,Aged ,VLAG ,business.industry ,Cancer ,PLASMA SEROTONIN ,Odds ratio ,medicine.disease ,kynurenine ,Logistic Models ,WHOLE-GRAIN INTAKE ,chemistry ,Case-Control Studies ,Serotonin ,business ,Kynurenine - 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 (OR) and 95% confidence intervals (CI) for colon cancer risk. Tryptophan was inversely associated with colon cancer risk in ColoCare [OR per 1-standard deviation (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 versus non-detectable 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. This article is protected by copyright. All rights reserved.
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- 2021
31. Metabolically-defined body size phenotypes and risk of endometrial cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)
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Nathalie Kliemann, Romain Ould Ammar, Carine Biessy, Audrey Gicquiau, Verena Katzke, Rudolf Kaaks, Anne Tjønneland, Anja Olsen, Maria-Jose Sánchez, Marta Crous-Bou, Fabrizio Pasanisi, Sandar Tin Tin, Aurora Perez-Cornago, Dagfinn Aune, Sofia Christakoudi, Alicia K. Heath, Sandra M. Colorado-Yohar, Sara Grioni, Guri Skeie, Hanna Sartor, Annika Idahl, Charlotta Rylander, Anne M. May, Elisabete Weiderpass, Heinz Freisling, Mary C. Playdon, Sabina Rinaldi, Neil Murphy, Inge Huybrechts, Laure Dossus, Marc J. Gunter, Kliemann, Nathalie, Ould Ammar, Romain, Biessy, Carine, Gicquiau, Audrey, Katzke, Verena, Kaaks, Rudolf, Tjoenneland, Anne, Olsen, Anja, Sánchez, Maria-Jose, Crous-Bou, Marta, Pasanisi, Fabrizio, Tin Tin, Sandar, Perez-Cornago, Aurora, Aune, Dagfinn, Christakoudi, Sofia, Heath, Alicia K, Colorado-Yohar, Sandra M, Grioni, Sara, Skeie, Guri, Sartor, Hanna, Idahl, Annika, Rylander, Charlotta, M May, Anne, Weiderpass, Elisabete, Freisling, Heinz, Playdon, Mary C, Rinaldi, Sabina, Murphy, Neil, Huybrechts, Inge, Dossus, Laure, and Gunter, Marc J
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Endometrial Neoplasms/complications ,Epidemiology ,Trastorns del metabolisme ,Risk factors in diseases ,C-PEPTIDE ,Body Mass Index ,MASS INDEX ,Endometrial cancer ,Risk Factors ,Body Size ,Humans ,Obesity ,Prospective Studies ,Factores de riesgo en enfermedades ,VALIDITY ,11 Medical and Health Sciences ,Cancer och onkologi ,INSULIN-RESISTANCE ,OVERWEIGHT ,C-Peptide ,Public Health, Global Health, Social Medicine and Epidemiology ,Endometrial Neoplasms ,Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi ,ESTROGEN ,Phenotype ,Disorders of metabolism ,Oncology ,Càncer d'endometri ,Case-Control Studies ,Cancer and Oncology ,OBESITY ,Obesitat ,GROWTH ,Female ,HEALTH ,Obesity/complications ,ANTHROPOMETRIC FACTORS - Abstract
Background: Obesity is a risk factor for endometrial cancer but whether metabolic dysfunction is associated with endometrial cancer independent of body size is not known. Methods: The association of metabolically defined body size phenotypes with endometrial cancer risk was investigated in a nested case–control study (817 cases/ 817 controls) within the European Prospective Investigation into Cancer and Nutrition (EPIC). Concentrations of C-peptide were used to define metabolically healthy (MH, World Health Organization, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Danish Cancer Society, Ligue nationale contre le cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (Inserm), Deutsche Krebshilfe, Helmholtz Association, German Institute of Human Nutrition PotsdamRehbruecke (DIfE), Federal Ministry of Education & Research (BMBF), Fondazione AIRC per la ricerca sul cancro, Compagnia di San Paolo, Consiglio Nazionale delle Ricerche (CNR), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds Netherlands Organization for Scientific Research (NWO), World Cancer Research Fund (WCRF-ERC) 232997, Netherlands Government, Health Research Fund (FIS)-Instituto de Salud Carlos III (ISCIII), Junta de Andalucia, Principality of Asturias, Basque Government, Regional Government of Murcia, Regional Government of Navarra, Catalan Institute of OncologyICO (Spain), Swedish Cancer Society Swedish Research Council, European Commission, County Council of Skane, County Council of Vasterbotten (Sweden), Cancer Research UK 14136 C8221/A29017 C19335/A21351, UK Research & Innovation (UKRI), Medical Research Council UK (MRC), European Commission 1000143 MR/M012190/1
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- 2022
32. Longitudinal associations of plasma metabolites with persistent fatigue among colorectal cancer survivors up to 2 years after treatment
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van Roekel, Eline H., primary, Bours, Martijn J. L., additional, Breukink, Stéphanie O., additional, Aquarius, Michèl, additional, Keulen, Eric T. P., additional, Gicquiau, Audrey, additional, Rinaldi, Sabina, additional, Vineis, Paolo, additional, Arts, Ilja C. W., additional, Gunter, Marc J., additional, Leitzmann, Michael F., additional, Scalbert, Augustin, additional, and Weijenberg, Matty P., additional
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- 2022
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33. Diet quality indices and dietary patterns are associated with plasma metabolites in colorectal cancer patients
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Dieuwertje E. Kok, Flip M. Kruyt, Augustin Scalbert, Pekka Keski-Rahkonen, Matty P. Weijenberg, Evertine Wesselink, Cornelia M. Ulrich, Moniek van Zutphen, Ellen Kampman, Fränzel J.B. Van Duijnhoven, Anne J.M.R. Geijsen, Johannes H. W. de Wilt, Audrey Gicquiau, Andrea Gsur, David Achaintre, RS: GROW - R1 - Prevention, and Epidemiologie
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Male ,Nutrition and Disease ,Colorectal cancer ,Metabolite ,Medicine (miscellaneous) ,Physiology ,Stage ii ,Body Mass Index ,chemistry.chemical_compound ,Colorectal cancer patients ,Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14] ,Voeding en Ziekte ,Metabolites ,Humans ,Medicine ,Metabolomics ,Dietary patterns ,Aged ,VLAG ,Nutrition and Dietetics ,business.industry ,Cancer ,Original Contribution ,Dietary pattern ,medicine.disease ,Diet ,Diet quality ,chemistry ,Diet quality indices ,Smoking status ,Diet, Healthy ,Colorectal Neoplasms ,business ,Body mass index - Abstract
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 AbsoluteIDQ 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.
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- 2021
34. Circulating Sex Hormone Levels and Colon Cancer Risk in Men : A Nested Case–Control Study and Meta-Analysis
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Harbs, Justin, Rinaldi, Sabina, Gicquiau, Audrey, Keski-Rahkonen, Pekka, Mori, Nagisa, Liu, Xijia, Kaaks, Rudolf, Katzke, Verena, Schulze, Matthias B., Agnoli, Claudia, Tumino, Rosario, Bueno-De-Mesquita, Bas, Crous-Bou, Marta, Sánchez, Maria-Jose, Aizpurua, Amaia, Chirlaque, María-Dolores, Gurrea, Aurelio Barricarte, Travis, Ruth C., Watts, Eleanor L., Christakoudi, Sofia, Tsilidis, Konstantinos K., Weiderpass, Elisabete, Gunter, Marc J., van Guelpen, Bethany, Murphy, Neil, Harlid, Sophia, Harbs, Justin, Rinaldi, Sabina, Gicquiau, Audrey, Keski-Rahkonen, Pekka, Mori, Nagisa, Liu, Xijia, Kaaks, Rudolf, Katzke, Verena, Schulze, Matthias B., Agnoli, Claudia, Tumino, Rosario, Bueno-De-Mesquita, Bas, Crous-Bou, Marta, Sánchez, Maria-Jose, Aizpurua, Amaia, Chirlaque, María-Dolores, Gurrea, Aurelio Barricarte, Travis, Ruth C., Watts, Eleanor L., Christakoudi, Sofia, Tsilidis, Konstantinos K., Weiderpass, Elisabete, Gunter, Marc J., van Guelpen, Bethany, Murphy, Neil, and Harlid, Sophia
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Background: Endogenous sex hormones may contribute to higher colorectal cancer incidence rates in men compared with women, but despite an increased number of studies, clear evidence is lacking. Methods: We conducted a comprehensive nested case–control study of circulating concentrations of sex hormones, sex hormone precursors, and sex hormone binding globulin (SHBG) in relation to subsequent colon cancer risk in European men. Concentrations were measured using liquid LC/MS-MS in prospectively collected plasma samples from 690 cases and 690 matched controls from the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Northern Sweden Health and Disease Study (NSHDS) cohorts. Multivariable conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). In addition, we conducted a meta-analysis of previous studies on men. Results: Circulating levels of testosterone (OR, 0.68; 95% CI, 0.51–0.89) and SHBG (OR, 0.77; 95% CI, 0.62–0.96) were inversely associated with colon cancer risk. For free testosterone, there was a nonsignificant inverse association (OR, 0.83; 95% CI, 0.58–1.18). In a dose–response meta-analysis of endogenous sex hormone levels, inverse associations with colorectal/colon cancer risk were found for testosterone [relative risks (RR) per 100 ng/dL ¼ 0.98; 95% CI, 0.96–1.00; I2 ¼ 22%] and free testosterone (RR per 1 ng/dL ¼ 0.98; 95% CI, 0.95–1.00; I2 ¼ 0%). Conclusions: Our results provide suggestive evidence for the association between testosterone, SHBG, and male colon cancer development. Impact: Additional support for the involvement of sex hormones in male colon cancer.
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- 2022
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35. Metabolically Defined Body Size Phenotypes and Risk of Endometrial Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)
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Kliemann, Nathalie, Ould Ammar, Romain, Biessy, Carine, Gicquiau, Audrey, Katzke, Verena, Kaaks, Rudolf, Tjønneland, Anne, Olsen, Anja, Sánchez, Maria-Jose, Crous-Bou, Marta, Pasanisi, Fabrizio, Tin Tin, Sandar, Perez-Cornago, Aurora, Aune, Dagfinn, Christakoudi, Sofia, Heath, Alicia K., Colorado-Yohar, Sandra M., Grioni, Sara, Skeie, Guri, Sartor, Hanna, Idahl, Annika, Rylander, Charlotta, May, Anne M., Weiderpass, Elisabete, Freisling, Heinz, Playdon, Mary C., Rinaldi, Sabina, Murphy, Neil, Huybrechts, Inge, Dossus, Laure, Gunter, Marc J., Kliemann, Nathalie, Ould Ammar, Romain, Biessy, Carine, Gicquiau, Audrey, Katzke, Verena, Kaaks, Rudolf, Tjønneland, Anne, Olsen, Anja, Sánchez, Maria-Jose, Crous-Bou, Marta, Pasanisi, Fabrizio, Tin Tin, Sandar, Perez-Cornago, Aurora, Aune, Dagfinn, Christakoudi, Sofia, Heath, Alicia K., Colorado-Yohar, Sandra M., Grioni, Sara, Skeie, Guri, Sartor, Hanna, Idahl, Annika, Rylander, Charlotta, May, Anne M., Weiderpass, Elisabete, Freisling, Heinz, Playdon, Mary C., Rinaldi, Sabina, Murphy, Neil, Huybrechts, Inge, Dossus, Laure, and Gunter, Marc J.
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BACKGROUND: Obesity is a risk factor for endometrial cancer but whether metabolic dysfunction is associated with endometrial cancer independent of body size is not known. METHODS: The association of metabolically defined body size phenotypes with endometrial cancer risk was investigated in a nested case-control study (817 cases/ 817 controls) within the European Prospective Investigation into Cancer and Nutrition (EPIC). Concentrations of C-peptide were used to define metabolically healthy (MH; <1st tertile) and metabolically unhealthy (MU; ≥1st tertile) status among the control participants. These metabolic health definitions were combined with normal weight (NW); body mass index (BMI)<25 kg/m2 or waist circumference (WC)<80 cm or waist-to-hip ratio (WHR)<0.8) and overweight (OW; BMI≥25 kg/m2 or WC≥80 cm or WHR≥0.8) status, generating four phenotype groups for each anthropometric measure: (i) MH/NW, (ii) MH/OW, (iii) MU/NW, and (iv) MU/OW. RESULTS: In a multivariable-adjusted conditional logistic regression model, compared with MH/NW individuals, endometrial cancer risk was higher among those classified as MU/NW [ORWC, 1.48; 95% confidence interval (CI), 1.05-2.10 and ORWHR, 1.68; 95% CI, 1.21-2.35] and MU/OW (ORBMI, 2.38; 95% CI, 1.73-3.27; ORWC, 2.69; 95% CI, 1.92-3.77 and ORWHR, 1.83; 95% CI, 1.32-2.54). MH/OW individuals were also at increased endometrial cancer risk compared with MH/NW individuals (ORWC, 1.94; 95% CI, 1.24-3.04). CONCLUSIONS: Women with metabolic dysfunction appear to have higher risk of endometrial cancer regardless of their body size. However, OW status raises endometrial cancer risk even among women with lower insulin levels, suggesting that obesity-related pathways are relevant for the development of this cancer beyond insulin. IMPACT: Classifying women by metabolic health may be of greater utility in identifying those at higher risk for endometrial cancer than anthropometry per se.
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- 2022
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36. Metabolic Signatures of Healthy Lifestyle Patterns and Colorectal Cancer Risk in a European Cohort.
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Rothwell, JA, Murphy, N, Bešević, J, Kliemann, N, Jenab, M, Ferrari, P, Achaintre, D, Gicquiau, A, Vozar, B, Scalbert, A, Huybrechts, I, Freisling, H, Prehn, C, Adamski, J, Cross, AJ, Pala, VM, Boutron-Ruault, M-C, Dahm, CC, Overvad, K, Gram, IT, Sandanger, TM, Skeie, G, Jakszyn, P, Tsilidis, KK, Aleksandrova, K, Schulze, MB, Hughes, DJ, van Guelpen, B, Bodén, S, Sánchez, M-J, Schmidt, JA, Katzke, V, Kühn, T, Colorado-Yohar, S, Tumino, R, Bueno-de-Mesquita, B, Vineis, P, Masala, G, Panico, S, Eriksen, AK, Tjønneland, A, Aune, D, Weiderpass, E, Severi, G, Chajès, V, Gunter, MJ, Rothwell, JA, Murphy, N, Bešević, J, Kliemann, N, Jenab, M, Ferrari, P, Achaintre, D, Gicquiau, A, Vozar, B, Scalbert, A, Huybrechts, I, Freisling, H, Prehn, C, Adamski, J, Cross, AJ, Pala, VM, Boutron-Ruault, M-C, Dahm, CC, Overvad, K, Gram, IT, Sandanger, TM, Skeie, G, Jakszyn, P, Tsilidis, KK, Aleksandrova, K, Schulze, MB, Hughes, DJ, van Guelpen, B, Bodén, S, Sánchez, M-J, Schmidt, JA, Katzke, V, Kühn, T, Colorado-Yohar, S, Tumino, R, Bueno-de-Mesquita, B, Vineis, P, Masala, G, Panico, S, Eriksen, AK, Tjønneland, A, Aune, D, Weiderpass, E, Severi, G, Chajès, V, and Gunter, MJ
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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.
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- 2022
37. Metabolically Defined Body Size Phenotypes and Risk of Endometrial Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)
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Kliemann, Nathalie, primary, Ould Ammar, Romain, additional, Biessy, Carine, additional, Gicquiau, Audrey, additional, Katzke, Verena, additional, Kaaks, Rudolf, additional, Tjønneland, Anne, additional, Olsen, Anja, additional, Sánchez, Maria-Jose, additional, Crous-Bou, Marta, additional, Pasanisi, Fabrizio, additional, Tin Tin, Sandar, additional, Perez-Cornago, Aurora, additional, Aune, Dagfinn, additional, Christakoudi, Sofia, additional, Heath, Alicia K., additional, Colorado-Yohar, Sandra M., additional, Grioni, Sara, additional, Skeie, Guri, additional, Sartor, Hanna, additional, Idahl, Annika, additional, Rylander, Charlotta, additional, May, Anne M., additional, Weiderpass, Elisabete, additional, Freisling, Heinz, additional, Playdon, Mary C., additional, Rinaldi, Sabina, additional, Murphy, Neil, additional, Huybrechts, Inge, additional, Dossus, Laure, additional, and Gunter, Marc J., additional
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- 2022
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38. Multi-omics Analysis Reveals Adipose-tumor Crosstalk in Patients with Colorectal Cancer
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Hans-Ulrich Kauczor, Johanna Nattenmüller, Martin Schneider, Stephen D. Hursting, Christy A. Warby, Biljana Gigic, Caroline Himbert, Alexis Ulrich, Peter Schirmacher, Jennifer Ose, Clare Abbenhardt-Martin, Richard Viskochil, Thomas Simon, Nina Habermann, Audrey Gicquiau, Magnus von Knebel-Doeberitz, Andrea Gsur, Juergen Boehm, Dieuwertje E. Kok, Augustin Scalbert, Tengda Lin, Pekka Keski-Rahkonen, David Achaintre, Matty P. Weijenberg, Kenneth M. Boucher, Cornelia M. Ulrich, Mariam Haffa, Esther Herpel, Andreana N. Holowatyj, Laura W. Bowers, Per M. Ueland, Dominique Scherer, Petra Schrotz-King, Matthias Kloor, RS: GROW - R1 - Prevention, and Epidemiologie
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0301 basic medicine ,tissue macrophages ,EXPRESSION ,Cancer Research ,Peroxisome proliferator-activated receptor gamma ,obesity ,Nutrition and Disease ,Carcinogenesis ,Colorectal cancer ,INHIBITION ,Adipose tissue ,Intra-Abdominal Fat ,serum c-peptide ,03 medical and health sciences ,0302 clinical medicine ,INFLAMMATION ,Fibrosis ,Voeding en Ziekte ,Tumor Microenvironment ,medicine ,Life Science ,Humans ,Serum amyloid A ,Receptor ,VLAG ,RISK ,colon ,business.industry ,medicine.disease ,modulation ,030104 developmental biology ,Adipose Tissue ,Oncology ,Adipogenesis ,FAT ,030220 oncology & carcinogenesis ,Cancer research ,GPVI ,Colorectal Neoplasms ,business - Abstract
Obesity and obesity-driven cancer rates are continuing to rise worldwide. We hypothesize that adipocyte–colonocyte interactions are a key driver of obesity-associated cancers. To understand the clinical relevance of visceral adipose tissue in advancing tumor growth, we analyzed paired tumor-adjacent visceral adipose, normal mucosa, and colorectal tumor tissues as well as presurgery blood samples from patients with sporadic colorectal cancer. We report that high peroxisome proliferator-activated receptor gamma (PPARG) visceral adipose tissue expression is associated with glycoprotein VI (GPVI) signaling—the major signaling receptor for collagen—as well as fibrosis and adipogenesis pathway signaling in colorectal tumors. These associations were supported by correlations between PPARG visceral adipose tissue expression and circulating levels of plasma 4-hydroxyproline and serum intercellular adhesion molecule 1 (ICAM1), as well as gene set enrichment analysis and joint gene-metabolite pathway results integration that yielded significant enrichment of genes defining epithelial-to-mesenchymal transition—as in fibrosis and metastasis—and genes involved in glycolytic metabolism, confirmed this association. We also reveal that elevated prostaglandin-endoperoxide synthase 2 (PTGS2) colorectal tumor expression is associated with a fibrotic signature in adipose–tumor crosstalk via GPVI signaling and dendritic cell maturation in visceral adipose tissue. Systemic metabolite and biomarker profiling confirmed that high PTGS2 expression in colorectal tumors is significantly associated with higher concentrations of serum amyloid A and glycine, and lower concentrations of sphingomyelin, in patients with colorectal cancer. This multi-omics study suggests that adipose–tumor crosstalk in patients with colorectal cancer is a critical microenvironment interaction that could be therapeutically targeted. See related spotlight by Colacino et al., p. 803
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- 2020
39. Circulating Sex Hormone Levels and Colon Cancer Risk in Men: A Nested Case–Control Study and Meta-Analysis
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Harbs, Justin, primary, Rinaldi, Sabina, additional, Gicquiau, Audrey, additional, Keski-Rahkonen, Pekka, additional, Mori, Nagisa, additional, Liu, Xijia, additional, Kaaks, Rudolf, additional, Katzke, Verena, additional, Schulze, Matthias B., additional, Agnoli, Claudia, additional, Tumino, Rosario, additional, Bueno-de-Mesquita, Bas, additional, Crous-Bou, Marta, additional, Sánchez, Maria-Jose, additional, Aizpurua, Amaia, additional, Chirlaque, María-Dolores, additional, Gurrea, Aurelio Barricarte, additional, Travis, Ruth C., additional, Watts, Eleanor L., additional, Christakoudi, Sofia, additional, Tsilidis, Konstantinos K., additional, Weiderpass, Elisabete, additional, Gunter, Marc J., additional, Van Guelpen, Bethany, additional, Murphy, Neil, additional, and Harlid, Sophia, additional
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- 2022
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40. Endogenous Circulating Sex Hormone Concentrations and Colon Cancer Risk in Postmenopausal Women: a Prospective Study and Meta-Analysis
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Matthias B. Schulze, Ruth C. Travis, Rosario Tumino, Rudolf Kaaks, Agnès Fournier, Niki Dimou, Pekka Keski-Rahkonen, Amanda J. Cross, Salvatore Panico, Marina Kvaskoff, Renée T. Fortner, María José Sánchez, Gianluca Severi, Dagfinn Aune, Carlotta Sacerdote, Marc J. Gunter, Konstantinos K. Tsilidis, Bas Bueno-de-Mesquita, Inger T. Gram, Eva Ardanaz, Sandra Colorado-Yohar, Marit Waaseth, Audrey Gicquiau, Vittorio Krogh, Paula Jakszyn, Sabina Rinaldi, Nagisa Mori, Justin Harbs, Neil Murphy, Sophia Harlid, Giovanna Masala, Eleanor L. Watts, and Bethany Van Guelpen
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Cancer Research ,Colorectal cancer ,Physiology ,chemistry.chemical_compound ,Sex hormone-binding globulin ,Sex Hormone-Binding Globulin ,Odds Ratio ,Testosterone ,Prospective Studies ,Prospective cohort study ,Gonadal Steroid Hormones ,Progesterone ,biology ,Estradiol ,VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801 ,Dehydroepiandrosterone Sulfate ,Middle Aged ,Europe ,Postmenopause ,Oncology ,Colonic Neoplasms ,Female ,Menopause ,AcademicSubjects/MED00010 ,Menopausa ,Estrone ,Dehydroepiandrosterone ,Article ,Càncer colorectal ,medicine ,Confidence Intervals ,Humans ,Androstenedione ,Cancer och onkologi ,business.industry ,Rectal Neoplasms ,Estrogens ,Odds ratio ,medicine.disease ,Logistic Models ,chemistry ,Cancer and Oncology ,Case-Control Studies ,biology.protein ,VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801 ,business - Abstract
This work was supported by the French National Cancer Institute (INCa SHSESP17, grant No. 2017-127 to N. Murphy). The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by: Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition PotsdamRehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (the Netherlands); Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology-ICO (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Ska degrees ne and V_asterbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C8221/A29017 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford) (United Kingdom)., Background: Observational studies have consistently reported that postmenopausal hormone therapy use is associated with lower colon cancer risk, but epidemiologic studies examining the associations between circulating concentrations of endogenous estrogens and colorectal cancer have reported inconsistent results. Methods: We investigated the associations between circulating concentrations of estrone, estradiol, free estradiol, testosterone, free testosterone, androstenedione, dehydroepiandrosterone (DHEA), progesterone, and sex hormone–binding globulin (SHBG) with colon cancer risk in a nested case-control study of 1028 postmenopausal European women (512 colon cancer cases, 516 matched controls) who were noncurrent users of exogenous hormones at blood collection. Multivariable conditional logistic regression models were used to compute odds ratios and 95% confidence intervals to evaluate the association between circulating sex hormones and colon cancer risk. We also conducted a dose-response meta-analysis of prospective studies of circulating estrone and estradiol with colorectal, colon, and rectal cancer risk in postmenopausal women. All statistical tests were 2-sided. Results: In the multivariable model, a nonstatistically significantly positive relationship was found between circulating estrone and colon cancer risk (odds ratio per log2 1-unit increment¼1.17 [95% confidence interval¼1.00 to 1.38]; odds ratioquartile4-quartile1¼1.33 [95% confidence interval¼0.89 to 1.97], Ptrend¼.20). Circulating concentrations of estradiol, free estradiol, testosterone, free testosterone, androstenedione, DHEA, progesterone, and SHBG were not associated with colon cancer risk. In the doseresponse meta-analysis, no clear evidence of associations were found between circulating estradiol and estrone concentrations with colorectal, colon, and rectal cancer risk. Conclusion: Our observational and meta-analysis results do not support an association between circulating concentrations of endogenous sex hormones and colon or rectal cancer in postmenopausal women., French National Cancer Institute (INCa SHSESP17) 2017-127, World Health Organization, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Danish Cancer Society, Ligue Contre le Cancer (France), Institut Gustave Roussy (France), Mutuelle Generale de l'Education Nationale (France), Institut National de la Sante et de la Recherche Medicale (Inserm), Deutsche Krebshilfe German Cancer Research Center (DKFZ) (Germany) German Institute of Human Nutrition Potsdam Rehbruecke (DIfE) (Germany), Federal Ministry of Education & Research (BMBF), Fondazione AIRC per la ricerca sul cancro, Compagnia di San Paolo Consiglio Nazionale delle Ricerche (CNR), Netherlands Government, World Cancer Research Fund International (WCRF), Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII) (Spain) Junta de Andalucia Regional Government of Asturias (Spain) Regional Government of Basque Country (Spain) Regional Government of Murcia (Spain) Regional Government of Navarra (Spain) Catalan Institute of Oncology-ICO (Spain), Swedish Cancer Society Swedish Research Council County Council of Skane (Sweden) County Council of Vasterbotten (Sweden), Cancer Research UK 14136 C8221/A29017 UK Research & Innovation (UKRI) Medical Research Council UK (MRC) 1000143 MR/M012190/1
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- 2021
41. A new pipeline for the normalization and pooling of metabolomics data
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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, IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, and Sub Inorganic Chemistry and Catalysis
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Normalization (statistics) ,Pooling ,Computer science ,Pipeline (computing) ,Endocrinology, Diabetes and Metabolism ,computer.software_genre ,Microbiology ,Biochemistry ,Generalized linear mixed model ,Statistical power ,Article ,03 medical and health sciences ,Endocrinology ,0302 clinical medicine ,Cancer epidemiology ,Metabolites ,Metabolomics ,Imputation (statistics) ,Càncer ,Molecular Biology ,030304 developmental biology ,Cancer ,0303 health sciences ,Cancer och onkologi ,Bioinformatics (Computational Biology) ,Normalization ,Technical variability ,VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801 ,Missing data ,QR1-502 ,3. Good health ,Diabetes and Metabolism ,Metabolòmica ,030220 oncology & carcinogenesis ,Cancer and Oncology ,Outlier ,Bioinformatik (beräkningsbiologi) ,Data mining ,VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801 ,computer - 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.
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- 2021
42. Longitudinal associations of plasma metabolites with persistent fatigue among colorectal cancer survivors up to 2 years after treatment.
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van Roekel, Eline H., Bours, Martijn J. L., Breukink, Stéphanie O., Aquarius, Michèl, Keulen, Eric T. P., Gicquiau, Audrey, Rinaldi, Sabina, Vineis, Paolo, Arts, Ilja C. W., Gunter, Marc J., Leitzmann, Michael F., Scalbert, Augustin, and Weijenberg, Matty P.
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COLORECTAL cancer ,CANCER survivors ,TANDEM mass spectrometry ,FALSE discovery rate ,METABOLITES - Abstract
The underlying biological mechanisms causing persistent fatigue complaints after colorectal cancer treatment need further investigation. We investigated longitudinal associations of circulating concentrations of 138 metabolites with total fatigue and subdomains of fatigue between 6 weeks and 2 years after colorectal cancer treatment. Among stage I‐III colorectal cancer survivors (n = 252), blood samples were obtained at 6 weeks, and 6, 12 and 24 months posttreatment. Total fatigue and fatigue subdomains were measured using a validated questionnaire. Tandem mass spectrometry was applied to measure metabolite concentrations (BIOCRATES AbsoluteIDQp180 kit). Confounder‐adjusted longitudinal associations were analyzed using linear mixed models, with false discovery rate (FDR) correction. We assessed interindividual (between‐participant differences) and intraindividual longitudinal associations (within‐participant changes over time). In the overall longitudinal analysis, statistically significant associations were observed for 12, 32, 17 and three metabolites with total fatigue and the subscales "fatigue severity," "reduced motivation" and "reduced activity," respectively. Specifically, higher concentrations of several amino acids, lysophosphatidylcholines, diacylphosphatidylcholines, acyl‐alkylphosphatidylcholines and sphingomyelins were associated with less fatigue, while higher concentrations of acylcarnitines were associated with more fatigue. For "fatigue severity," associations appeared mainly driven by intraindividual associations, while for "reduced motivation" stronger interindividual associations were found. We observed longitudinal associations of several metabolites with total fatigue and fatigue subscales, and that intraindividual changes in metabolites over time were associated with fatigue severity. These findings point toward inflammation and an impaired energy metabolism due to mitochondrial dysfunction as underlying mechanisms. Mechanistic studies are necessary to determine whether these metabolites could be targets for intervention. [ABSTRACT FROM AUTHOR]
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- 2023
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43. A new pipeline for the normalization and pooling of metabolomics data
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Reza M. Salek, Kim Overvad, Charlotte Onland, Matthias B. Schulze, Rudolf Kaaks, Sabina Rinaldi, Domenico Palli, Gianluca Severi, Vivian Viallon, Filip Ottoson, Mathilde His, Salvatore Panico, Ruth C. Travis, José María Huerta, Joseph A. Rothwell, Claudia Agnoli, Pekka Keski-Rahkonen, Elisabete Weiderpass, Theron Johnson, Audrey Gicquiau, Monique Verschuren, Peter M. Engelfriet, Julie A. Schmidt, Ilona Urbarova, Pilar Amiano, Mattias Johansson, Rosario Tumino, Agnetha Linn Rostgaard-Hansen, Eva Ardanaz, Roel Vermeulen, Lucie Lecuyer, Mazda Jenab, Matilda Rentoft, Fulvio Ricceri, Raul Zamora-Ros, Bertrand Hémon, Linda Vidman, Pietro Ferrari, Anne Tjønneland, Laure Dossus, Marc J. Gunter, Olle Melander, Miguel Rodríguez-Barranco, Therese Haugdahl Nøst, Dominique Scherer, Lorenzo Bermejo, and Marie Breeur
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Normalization (statistics) ,Computer science ,Pipeline (computing) ,Pooling ,Outlier ,Data mining ,Imputation (statistics) ,computer.software_genre ,Missing data ,computer ,Statistical power ,Generalized linear mixed model - 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 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.
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- 2021
44. Longitudinal associations of physical activity with plasma metabolites among colorectal cancer survivors up to 2 years after treatment
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Marc J. Gunter, Ilja C. W. Arts, Stephanie O. Breukink, Eline H. van Roekel, Michel Aquarius, Vivian Viallon, Linda van Delden, Augustin Scalbert, Michael F. Leitzmann, Sabina Rinaldi, Eric T.P. Keulen, Matty P. Weijenberg, Paolo Vineis, Audrey Gicquiau, Martijn J.L. Bours, Epidemiologie, RS: GROW - R1 - Prevention, RS: CAPHRI - R3 - Functioning, Participating and Rehabilitation, Surgery, MUMC+: MA Heelkunde (9), RS: NUTRIM - R2 - Liver and digestive health, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Maastricht Centre for Systems Biology, RS: FHML MaCSBio, RS: FPN MaCSBio, RS: FSE MaCSBio, and RS: Carim - V01 Vascular complications of diabetes and metabolic syndrome
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Male ,0301 basic medicine ,Arginine ,Epidemiology ,Colorectal cancer ,Metabolite ,SERUM ,chemistry.chemical_compound ,0302 clinical medicine ,Cancer Survivors ,Tandem Mass Spectrometry ,QUALITY-OF-LIFE ,Interquartile range ,REPRODUCIBILITY ,Citrulline ,Longitudinal Studies ,Multidisciplinary ,Middle Aged ,Sphingomyelins ,030220 oncology & carcinogenesis ,TARGETED METABOLOMICS ,Plasma concentration ,Metabolome ,Medicine ,Female ,HEALTH ,Colorectal Neoplasms ,After treatment ,medicine.medical_specialty ,Science ,BIOMARKERS ,QUESTIONNAIRE ,Physical activity ,Article ,CLASSIFICATION ,Gastrointestinal cancer ,03 medical and health sciences ,Cancer epidemiology ,Carnitine ,Internal medicine ,medicine ,Humans ,Metabolomics ,Histidine ,Exercise ,SIGNATURES ,Aged ,business.industry ,MORTALITY ,Lysophosphatidylcholines ,medicine.disease ,030104 developmental biology ,Endocrinology ,Risk factors ,chemistry ,Quality of Life ,Self Report ,business - Abstract
We investigated longitudinal associations of moderate-to-vigorous physical activity (MVPA) and light-intensity physical activity (LPA) with plasma concentrations of 138 metabolites after colorectal cancer (CRC) treatment. Self-reported physical activity data and blood samples were obtained at 6 weeks, and 6, 12 and 24 months post-treatment in stage I-III CRC survivors (n = 252). Metabolite concentrations were measured by tandem mass spectrometry (BIOCRATES AbsoluteIDQp180 kit). Linear mixed models were used to evaluate confounder-adjusted longitudinal associations. Inter-individual (between-participant differences) and intra-individual associations (within-participant changes over time) were assessed as percentage difference in metabolite concentration per 5 h/week of MVPA or LPA. At 6 weeks post-treatment, participants reported a median of 6.5 h/week of MVPA (interquartile range:2.3,13.5) and 7.5 h/week of LPA (2.0,15.8). Inter-individual associations were observed with more MVPA being related (FDR-adjusted q-value
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- 2021
45. Biomarkers of mammographic density in premenopausal women
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Audrey Gicquiau, Vivian Viallon, Liliana Gómez-Flores-Ramos, Adriana Monge, Sabina Rinaldi, Mathilde His, Martin Lajous, Carine Biessy, Laure Dossus, and Marc J. Gunter
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0301 basic medicine ,Oncology ,Adult ,medicine.medical_specialty ,Breast Neoplasms ,Body Mass Index ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Breast cancer ,Risk Factors ,Internal medicine ,Linear regression ,Medicine ,Humans ,Metabolomics ,Breast ,Mammographic density ,Mexico ,RC254-282 ,Mexican women ,Breast Density ,Premenopausal ,business.industry ,Cholesterol ,MAMMOGRAPHIC DENSITY ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Targeted metabolomics ,Middle Aged ,medicine.disease ,Sphingomyelins ,030104 developmental biology ,Cross-Sectional Studies ,chemistry ,Premenopause ,Risk factors for breast cancer ,030220 oncology & carcinogenesis ,Cohort ,Phosphatidylcholines ,Female ,Metabolic syndrome ,business ,Body mass index ,Biomarkers ,Research Article ,Mammography - Abstract
Background While mammographic density is one of the strongest risk factors for breast cancer, little is known about its determinants, especially in young women. We applied targeted metabolomics to identify circulating metabolites specifically associated with mammographic density in premenopausal women. Then, we aimed to identify potential correlates of these biomarkers to guide future research on potential modifiable determinants of mammographic density. Methods A total of 132 metabolites (acylcarnitines, amino acids, biogenic amines, glycerophospholipids, sphingolipids, hexose) were measured by tandem liquid chromatography/mass spectrometry in plasma samples from 573 premenopausal participants in the Mexican Teachers’ Cohort. Associations between metabolites and percent mammographic density were assessed using linear regression models, adjusting for breast cancer risk factors and accounting for multiple tests. Mean concentrations of metabolites associated with percent mammographic density were estimated across levels of several lifestyle and metabolic factors. Results Sphingomyelin (SM) C16:1 and phosphatidylcholine (PC) ae C30:2 were inversely associated with percent mammographic density after correction for multiple tests. Linear trends with percent mammographic density were observed for SM C16:1 only in women with body mass index (BMI) below the median (27.4) and for PC ae C30:2 in women with a BMI over the median. SM C16:1 and PC ae C30:2 concentrations were positively associated with cholesterol (total and HDL) and inversely associated with number of metabolic syndrome components. Conclusions We identified new biomarkers associated with mammographic density in young women. The association of these biomarkers with mammographic density and metabolic parameters may provide new perspectives to support future preventive actions for breast cancer.
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- 2021
46. Endogenous Circulating Sex Hormone Concentrations and Colon Cancer Risk in Postmenopausal Women: A Prospective Study and Meta-Analysis
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Mori, Nagisa, primary, Keski-Rahkonen, Pekka, additional, Gicquiau, Audrey, additional, Rinaldi, Sabina, additional, Dimou, Niki, additional, Harlid, Sophia, additional, Harbs, Justin, additional, Van Guelpen, Bethany, additional, Aune, Dagfinn, additional, Cross, Amanda J, additional, Tsilidis, Konstantinos K, additional, Severi, Gianluca, additional, Kvaskoff, Marina, additional, Fournier, Agnès, additional, Kaaks, Rudolf, additional, Fortner, Renée Turzanski, additional, Schulze, Matthias B, additional, Jakszyn, Paula, additional, Sánchez, Maria-Jose, additional, Colorado-Yohar, Sandra M, additional, Ardanaz, Eva, additional, Travis, Ruth, additional, Watts, Eleanor L, additional, Masala, Giovanna, additional, Krogh, Vittorio, additional, Tumino, Rosario, additional, Sacerdote, Carlotta, additional, Panico, Salvatore, additional, Bueno-de-Mesquita, Bas, additional, Gram, Inger Torhild, additional, Waaseth, Marit, additional, Gunter, Marc J, additional, and Murphy, Neil, additional
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- 2021
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47. Metabolic signatures of greater body size and their associations with risk of colorectal and endometrial cancers in the European Prospective Investigation into Cancer and Nutrition
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Augustin Scalbert, Salvatore Panico, Pietro Ferrari, Bas Bueno-de-Mesquita, Mattias Johansson, Matthias B. Schulze, Krasimira Aleksandrova, Claudia Agnoli, Sabina Rinaldi, Hector C. Keun, José María Huerta, Rebecca J. Beeken, Joseph A. Rothwell, David Achaintre, Julie A. Schmidt, Marc J. Gunter, Eline H. van Roekel, Vivian Viallon, Nathalie Kliemann, Giovanna Masala, Renée T. Fortner, Neil Murphy, Ann H. Rosendahl, Hanna Sartor, Alicia K Heath, Audrey Gicquiau, Kristin Benjaminsen Borch, Anne Tjønneland, Konstantinos K. Tsilidis, Laure Dossus, Ruth C. Travis, Mazda Jenab, Nada Assi, Bethany Van Guelpen, Rudolf Kaaks, Jytte Halkjær, Centre international de Recherche sur le Cancer (CIRC), University of Leeds, University College of London [London] (UCL), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Gustave Roussy (IGR), Maastricht University [Maastricht], University of Oxford [Oxford], The Arctic University of Norway (UiT), Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], Skane University Hospital [Lund], Lund University [Lund], CIBER de Epidemiología y Salud Pública (CIBERESP), Murcia Regional Health Council [Murcia], Danish Cancer Society Research Center [Copenhagen, Denmark] (DCSRC), National Institute for Public Health and the Environment [Bilthoven] (RIVM), University of Potsdam, German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Imperial College London, University of Ioannina, Istituto per lo Studio, la Prevenzione e la rete Oncologica [Florence, Italy] (ISPRO), Université de Naples, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Umeå University, Cancer Research UK, Epidemiologie, RS: GROW - R1 - Prevention, University of Oxford, The Arctic University of Norway [Tromsø, Norway] (UiT), University of Potsdam = Universität Potsdam, and Malbec, Odile
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0301 basic medicine ,Oncology ,Weight loss ,Colorectal cancer ,[SDV]Life Sciences [q-bio] ,Body Mass Index ,0302 clinical medicine ,Risk Factors ,Medicine ,Body Size ,Mass index ,Prospective Studies ,OXIDATIVE STRESS ,11 Medical and Health Sciences ,Cancer ,2. Zero hunger ,INSULIN-RESISTANCE ,Public Health, Global Health, Social Medicine and Epidemiology ,General Medicine ,European Prospective Investigation into Cancer and Nutrition ,[SDV] Life Sciences [q-bio] ,030220 oncology & carcinogenesis ,OBESITY ,Female ,medicine.symptom ,Waist Circumference ,Colorectal Neoplasms ,Life Sciences & Biomedicine ,Research Article ,medicine.medical_specialty ,BIOMARKERS ,Context (language use) ,03 medical and health sciences ,Medicine, General & Internal ,MASS INDEX ,LUNG-CANCER ,Internal medicine ,General & Internal Medicine ,Humans ,Metabolomics ,BREAST-CANCER ,Obesity ,VALIDITY ,BARIATRIC SURGERY ,Cancer och onkologi ,Science & Technology ,business.industry ,Endometrial cancer ,medicine.disease ,Endometrial Neoplasms ,Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi ,030104 developmental biology ,Logistic Models ,Cancer and Oncology ,WEIGHT ,business ,Body mass index - Abstract
Background The mechanisms underlying the obesity-cancer relationship are incompletely understood. This study aimed to characterise metabolic signatures of greater body size and to investigate their association with two obesity-related malignancies, endometrial and colorectal cancers, and with weight loss within the context of an intervention study. Methods Targeted mass spectrometry metabolomics data from 4326 participants enrolled in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort and 17 individuals from a single-arm pilot weight loss intervention (Intercept) were used in this analysis. Metabolic signatures of body size were first determined in discovery (N = 3029) and replication (N = 1297) sets among EPIC participants by testing the associations between 129 metabolites and body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) using linear regression models followed by partial least squares analyses. Conditional logistic regression models assessed the associations between the metabolic signatures with endometrial (N = 635 cases and 648 controls) and colorectal (N = 423 cases and 423 controls) cancer risk using nested case-control studies in EPIC. Pearson correlation between changes in the metabolic signatures and weight loss was tested among Intercept participants. Results After adjustment for multiple comparisons, greater BMI, WC, and WHR were associated with higher levels of valine, isoleucine, glutamate, PC aa C38:3, and PC aa C38:4 and with lower levels of asparagine, glutamine, glycine, serine, lysoPC C17:0, lysoPC C18:1, lysoPC C18:2, PC aa C42:0, PC ae C34:3, PC ae C40:5, and PC ae C42:5. The metabolic signature of BMI (OR1-sd 1.50, 95% CI 1.30–1.74), WC (OR1-sd 1.46, 95% CI 1.27–1.69), and WHR (OR1-sd 1.54, 95% CI 1.33–1.79) were each associated with endometrial cancer risk. Risk of colorectal cancer was positively associated with the metabolic signature of WHR (OR1-sd: 1.26, 95% CI 1.07–1.49). In the Intercept study, a positive correlation was observed between weight loss and changes in the metabolic signatures of BMI (r = 0.5, 95% CI 0.06–0.94, p = 0.03), WC (r = 0.5, 95% CI 0.05–0.94, p = 0.03), and WHR (r = 0.6, 95% CI 0.32–0.87, p = 0.01). Conclusions Obesity is associated with a distinct metabolic signature comprising changes in levels of specific amino acids and lipids which is positively associated with both colorectal and endometrial cancer and is potentially reversible following weight loss.
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- 2021
48. Targeted Plasma Metabolic Profiles and Risk of Recurrence in Stage II and III Colorectal Cancer Patients: Results from an International Cohort Consortium
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Nivonirina Robinot, Andreana N. Holowatyj, Alexis Ulrich, Audrey Gicquiau, Annaleen Koole, Arve Ulvik, Augustin Scalbert, Tengda Lin, Jennifer Ose, Pekka Keski-Rahkonen, Per-Magne Ueland, Martin Schneider, Biljana Gigic, Matty P. Weijenberg, David Achaintre, Eline van van Roekel, Cornelia M. Ulrich, Anne J.M.R. Geijsen, Tanja Gumpenberger, Fränzel J.B. Van Duijnhoven, Andreas Baierl, Andrea Gsur, Dieuwertje E. Kok, Petra Schrotz-King, Stefanie Brezina, Nina Habermann, RS: GROW - R1 - Prevention, and Epidemiologie
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0301 basic medicine ,False discovery rate ,Oncology ,medicine.medical_specialty ,recurrence ,Nutrition and Disease ,Colorectal cancer ,Endocrinology, Diabetes and Metabolism ,lcsh:QR1-502 ,colorectal cancer ,Stage ii ,Biochemistry ,lcsh:Microbiology ,Article ,03 medical and health sciences ,0302 clinical medicine ,Metabolomics ,Recurrence ,Internal medicine ,Voeding en Ziekte ,COLON ,medicine ,targeted metabolomics ,Prospective cohort study ,Molecular Biology ,business.industry ,Targeted metabolomics ,medicine.disease ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cohort ,Multiple comparisons problem ,SURVIVAL ,LIFE-STYLE ,business ,Body mass index - Abstract
The identification of patients at high-risk for colorectal cancer (CRC) recurrence remains an unmet clinical need. The aim of this study was to investigate associations of metabolites with risk of recurrence in stage II/III CRC patients. A targeted metabolomics assay (128 metabolites measured) was performed on pre-surgery collected EDTA plasma samples from n = 440 newly diagnosed stage II/III CRC patients. Patients have been recruited from four prospective cohort studies as part of an international consortium: Metabolomic profiles throughout the continuum of CRC (MetaboCCC). Cox proportional hazard models were computed to investigate associations of metabolites with recurrence, adjusted for age, sex, tumor stage, tumor site, body mass index, and cohort, false discovery rate (FDR) was used to account for multiple testing. Sixty-nine patients (15%) had a recurrence after a median follow-up time of 20 months. We identified 13 metabolites that were nominally associated with a reduced risk of recurrence. None of the associations were statistically significant after controlling for multiple testing. Pathway topology analyses did not reveal statistically significant associations between recurrence and alterations in metabolic pathways (e.g., sphingolipid metabolism p = 0.04, pFDR = 1.00). To conclude, we did not observe statistically significant associations between metabolites and CRC recurrence using a well-established metabolomics assay. The observed results require follow-up in larger studies.
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- 2021
49. A new pipeline for the normalization and pooling of metabolomics data
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Viallon, Vivian, primary, His, Mathilde, additional, Rinaldi, Sabina, additional, Breeur, Marie, additional, Gicquiau, Audrey, additional, Hemon, Bertrand, additional, Overvad, Kim, additional, Tjønneland, Anne, additional, Rostgaard-Hansen, Agnetha Linn, additional, Rothwell, Joseph A., additional, Lecuyer, Lucie, additional, Severi, Gianluca, additional, Kaaks, Rudolf, additional, Johnson, Theron, additional, Schulze, Matthias B., additional, Palli, Domenico, additional, Agnoli, Claudia, additional, Panico, Salvatore, additional, Tumino, Rosario, additional, Ricceri, Fulvio, additional, Verschuren, Monique, additional, Engelfriet, Peter, additional, Onland, Charlotte, additional, Vermeulen, Roel, additional, Nøst, Therese Haugdahl, additional, Urbarova, Ilona, additional, Zamora-Ros, Raul, additional, Rodriguez-Barranco, Miguel, additional, Amiano, Pilar, additional, Huerta, José Maria, additional, Ardanaz, Eva, additional, Melander, Olle, additional, Ottoson, Filip, additional, Vidman, Linda, additional, Rentoft, Matilda, additional, Schmidt, Julie A, additional, Travis, Ruth C, additional, Weiderpass, Elisabete, additional, Johansson, Mattias, additional, Dossus, Laure, additional, Jenab, Mazda, additional, Gunter, Marc J, additional, Bermejo, Lorenzo, additional, Scherer, Dominique, additional, Salek, Reza M, additional, Keski-Rahkonen, Pekka, additional, and Ferrari, Pietro, additional
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- 2021
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50. Circulating tryptophan metabolites and risk of colon cancer: Results from case‐control and prospective cohort studies
- Author
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Papadimitriou, Nikos, primary, Gunter, Marc J., additional, Murphy, Neil, additional, Gicquiau, Audrey, additional, Achaintre, David, additional, Brezina, Stefanie, additional, Gumpenberger, Tanja, additional, Baierl, Andreas, additional, Ose, Jennifer, additional, Geijsen, Anne J. M. R., additional, van Roekel, Eline H., additional, Gsur, Andrea, additional, Gigic, Biljana, additional, Habermann, Nina, additional, Ulrich, Cornelia M., additional, Kampman, Ellen, additional, Weijenberg, Matty P., additional, Ueland, Per Magne, additional, Kaaks, Rudolf, additional, Katzke, Verena, additional, Krogh, Vittorio, additional, Bueno‐de‐Mesquita, Bas, additional, Ardanaz, Eva, additional, Travis, Ruth C., additional, Schulze, Matthias B., additional, Sánchez, Maria‐José, additional, Colorado‐Yohar, Sandra M., additional, Weiderpass, Elisabete, additional, Scalbert, Augustin, additional, and Keski‐Rahkonen, Pekka, additional
- Published
- 2021
- Full Text
- View/download PDF
Catalog
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