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1. Dietary fatty acids and endometrial cancer risk within the European Prospective Investigation into Cancer and Nutrition

Author: Yammine, S. G., Huybrechts, I., Biessy, C., Dossus, L., Panico, S., Sánchez, M. J., Benetou, V., Turzanski-Fortner, R., Katzke, V., Idahl, A., Skeie, G., Olsen, K. Standahl, Tjønneland, A., Halkjaer, J., Colorado-Yohar, S., Heath, A. K., Sonestedt, E., Sartor, H., Schulze, M. B., Palli, D., Crous-Bou, M., Dorronsoro, A., Overvad, K., Gurrea, A. Barricarte, Severi, G., Vermeulen, R. C.H., Sandanger, T. M., Travis, R. C., Key, T., Amiano, P., Van Guelpen, B., Johansson, M., Sund, M., Tumino, R., Wareham, N., Sacerdote, C., Krogh, V., Brennan, P., Riboli, E., Weiderpass, E., Gunter, M. J., and Chajès, V.
Published: 2023
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2. Dietary intake of advanced glycation end products (AGEs) and changes in body weight in European adults

Author: Cordova, R., Knaze, V., Viallon, V., Rust, P., Schalkwijk, C. G., Weiderpass, E., Wagner, K-H., Mayen-Chacon, A-L., Aglago, E. K., Dahm, C. C., Overvad, K., Tjønneland, A., Halkjær, J., Mancini, F. R., Boutron-Ruault, M-C., Fagherazzi, G., Katzke, V., Kühn, T., Schulze, M. B., Boeing, H., Trichopoulou, A., Karakatsani, A., Thriskos, P., Masala, G., Krogh, V., Panico, S., Tumino, R., Ricceri, F., Spijkerman, A., Boer, J., Skeie, G., Rylander, C., Borch, K. B., Quirós, J. R., Agudo, A., Redondo-Sánchez, D., Amiano, P., Gómez-Gómez, J-H., Barricarte, A., Ramne, S., Sonestedt, E., Johansson, I., Esberg, A., Tong, T., Aune, D., Tsilidis, K. K., Gunter, M. J., Jenab, M., and Freisling, Heinz
Published: 2020
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3. Prediagnostic transcriptomic markers of Chronic lymphocytic leukemia reveal perturbations 10 years before diagnosis

Author: Chadeau-Hyam, M, Vermeulen, RCH, Hebels, DGAJ, Castagné, R, Campanella, G, Portengen, L, Kelly, RS, Bergdahl, IA, Melin, B, Hallmans, G, Palli, D, Krogh, V, Tumino, R, Sacerdote, C, Panico, S, de Kok, TMCM, Smith, MT, Kleinjans, JCS, Vineis, P, Kyrtopoulos, SA, consortium, on behalf of the EnviroGenoMarkers project, Georgiadis, P, Botsivali, M, Papadopoulou, C, Chatziioannou, A, Valavanis, I, Gottschalk, R, van Leeuwen, D, Timmermans, L, Keun, HC, Athersuch, TJ, Lenner, P, Bendinelli, B, Stephanou, EG, Myridakis, A, Kogevinas, M, Saberi-Hosnijeh, F, Fazzo, L, de Santis, M, Comba, P, Kiviranta, H, Rantakokko, P, Airaksinen, R, Ruokojarvi, P, Gilthorpe, MS, Fleming, S, Fleming, T, Tu, Y-K, Jonsson, B, Lundh, T, Chien, K-L, Chen, WJ, Lee, W-C, Hsiao, CK, Kuo, P-H, Hung, H, and Liao, S-F
Subjects: Genetic Testing, Lymphoma, Orphan Drug, Genetics, Hematology, Cancer, Rare Diseases, Clinical Research, 2.1 Biological and endogenous factors, Aetiology, Adult, Aged, Biomarkers, Tumor, Case-Control Studies, Female, Genome, Human, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Male, Middle Aged, Models, Genetic, Principal Component Analysis, Prospective Studies, Transcriptome, epidemiology, lymphoma, chronic lymphocytic leukemia, mRNA analyses, prospective cohort, EnviroGenoMarkers project consortium, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract: BackgroundB-cell lymphomas are a diverse group of hematological neoplasms with differential etiology and clinical trajectories. Increased insights in the etiology and the discovery of prediagnostic markers have the potential to improve the clinical course of these neoplasms.MethodsWe investigated in a prospective study global gene expression in peripheral blood mononuclear cells of 263 incident B-cell lymphoma cases, diagnosed between 1 and 17 years after blood sample collection, and 439 controls, nested within two European cohorts.ResultsOur analyses identified only transcriptomic markers for specific lymphoma subtypes; few markers of multiple myeloma (N = 3), and 745 differentially expressed genes in relation to future risk of chronic lymphocytic leukemia (CLL). The strongest of these associations were consistently found in both cohorts and were related to (B-) cell signaling networks and immune system regulation pathways. CLL markers exhibited very high predictive abilities of disease onset even in cases diagnosed more than 10 years after blood collection.ConclusionsThis is the first investigation on blood cell global gene expression and future risk of B-cell lymphomas. We mainly identified genes in relation to future risk of CLL that are involved in biological pathways, which appear to be mechanistically involved in CLL pathogenesis. Many but not all of the top hits we identified have been reported previously in studies based on tumor tissues, therefore suggesting that a mixture of preclinical and early disease markers can be detected several years before CLL clinical diagnosis.
Published: 2014

4. Dietary fatty acids and endometrial cancer risk within the European Prospective Investigation into Cancer and Nutrition

Author: IRAS OH Epidemiology Chemical Agents, Yammine, S G, Huybrechts, I, Biessy, C, Dossus, L, Panico, S, Sánchez, M J, Benetou, V, Turzanski-Fortner, R, Katzke, V, Idahl, A, Skeie, G, Olsen, K Standahl, Tjønneland, A, Halkjaer, J, Colorado-Yohar, S, Heath, A K, Sonestedt, E, Sartor, H, Schulze, M B, Palli, D, Crous-Bou, M, Dorronsoro, A, Overvad, K, Gurrea, A Barricarte, Severi, G, Vermeulen, R C H, Sandanger, T M, Travis, R C, Key, T, Amiano, P, Van Guelpen, B, Johansson, M, Sund, M, Tumino, R, Wareham, N, Sacerdote, C, Krogh, V, Brennan, P, Riboli, E, Weiderpass, E, Gunter, M J, Chajès, V, IRAS OH Epidemiology Chemical Agents, Yammine, S G, Huybrechts, I, Biessy, C, Dossus, L, Panico, S, Sánchez, M J, Benetou, V, Turzanski-Fortner, R, Katzke, V, Idahl, A, Skeie, G, Olsen, K Standahl, Tjønneland, A, Halkjaer, J, Colorado-Yohar, S, Heath, A K, Sonestedt, E, Sartor, H, Schulze, M B, Palli, D, Crous-Bou, M, Dorronsoro, A, Overvad, K, Gurrea, A Barricarte, Severi, G, Vermeulen, R C H, Sandanger, T M, Travis, R C, Key, T, Amiano, P, Van Guelpen, B, Johansson, M, Sund, M, Tumino, R, Wareham, N, Sacerdote, C, Krogh, V, Brennan, P, Riboli, E, Weiderpass, E, Gunter, M J, and Chajès, V
Published: 2023

5. Prediagnostic transcriptomic markers of Chronic lymphocytic leukemia reveal perturbations 10 years before diagnosis

Author: Georgiadis, P., Botsivali, M., Papadopoulou, C., Chatziioannou, A., Valavanis, I., Gottschalk, R., van Leeuwen, D., Timmermans, L., Keun, H.C., Athersuch, T.J., Lenner, P., Bendinelli, B., Stephanou, E.G., Myridakis, A., Kogevinas, M., Saberi-Hosnijeh, F., Fazzo, L., de Santis, M., Comba, P., Kiviranta, H., Rantakokko, P., Airaksinen, R., Ruokojarvi, P., Gilthorpe, M.S., Fleming, S., Fleming, T., Tu, Y.-K., Jonsson, B., Lundh, T., Chien, K.-L., Chen, W.J., Lee, W.-C., Hsiao, C.K., Kuo, P.-H., Hung, H., Liao, S.-F., Chadeau-Hyam, M., Vermeulen, R.C.H., Hebels, D.G.A.J., Castagné, R., Campanella, G., Portengen, L., Kelly, R.S., Bergdahl, I.A., Melin, B., Hallmans, G., Palli, D., Krogh, V., Tumino, R., Sacerdote, C., Panico, S., de Kok, T.M.C.M., Smith, M.T., Kleinjans, J.C.S., Vineis, P., and Kyrtopoulos, S.A.
Published: 2014
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6. Validity of 24-h recalls in (pre-)school aged children: Comparison of proxy-reported energy intakes with measured energy expenditure

Author: Börnhorst, C., Bel-Serrat, S., Pigeot, I., Huybrechts, I., Ottavaere, C., Sioen, I., De Henauw, S., Mouratidou, T., Mesana, M.I., Westerterp, K., Bammann, K., Lissner, L., Eiben, G., Pala, V., Rayson, M., Krogh, V., and Moreno, L.A.
Published: 2014
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7. Physical activity, sex steroid, and growth factor concentrations in pre- and post-menopausal women: a cross-sectional study within the EPIC cohort

Author: Rinaldi, S., Kaaks, R., Friedenreich, C. M., Key, T. J., Travis, R., Biessy, C., Slimani, N., Overvad, K., Østergaard, J. N., Tjønneland, A., Olsen, A., Mesrine, S., Fournier, A., Dossus, L., Lukanova, A., Johnson, T., Boeing, H., Vigl, M., Trichopoulou, A., Benetou, V., Trichopoulos, D., Masala, G., Krogh, V., Tumino, R., Ricceri, F., Panico, S., Bueno-de-Mesquita, H. B., Monninkhof, E. M., May, A. M., Weiderpass, E., Quirós, J. R., Travier, N., Molina-Montes, E., Amiano, P., Huerta, J. M., Ardanaz, E., Sund, M., Johansson, M., Khaw, K. T., Wareham, N., Scalbert, A., Gunter, M. J., Riboli, E., and Romieu, I.
Published: 2014

8. Flavonoid and lignan intake in a mediterranean population: proposal for a holistic approach in polyphenol dietary analysis, the Moli-sani study

Author: Pounis, G., Castelnuovo, A. Di, Bonaccio, M., Costanzo, S., Persichillo, M., Krogh, V., Donati, M.B., de Gaetano, G., and Iacoviello, L.
Subjects: Flavonoids -- Health aspects, Lignin -- Health aspects, Polyphenols -- Health aspects, Food/cooking/nutrition, Health
Abstract: BACKGROUND/OBJECTIVES: The objective of this study is to extract and assess data on the dietary intake of flavonoids and lignans in a healthy free-living Mediterranean population, using newly updated harmonized European Union food composition data. This work also aimed at analyzing in a holistic way the total content of the diet in major classes of polyphenols. SUBJECTS/METHODS: Six thousand nine hundred and eighty-one men and 7 048 women (aged [greater than or equal to] 35years) of the Moli-sani cohort, randomly recruited from the general population, were analyzed. The European Prospective Investigation into Cancer (EPIC) and Nutrition-Food Frequency Questionnaire was used for dietary assessment. The polyphenol content of each food group was evaluated using Eurofir BioActive Substances in Food Information System and the United States Department of Agriculture food composition tables (FCTs), when data were missing. Flavonol, flavone, flavanone, flavanol, anthocyanin, isoflavone and lignan intakes were calculated and polyphenol antioxidant content (PAC) score (-28, 28) constructed, to assess the total content of the diet in these nutrients. RESULTS: Seasonal and citrus fruits, leafy, grain, pod and root vegetables, and onions and garlic accounted for different proportions (11-70%) of the total intake of different polyphenols. Within the Moli-sani population, men or older, or no/former smokers, or physically active or obese/overweight individuals presented higher consumption of flavonoids, lignans and PAC score (P for all < 0.01). Multiple regression analysis showed that PAC score and its seven components were positively associated with Mediterranean diet (MeD) adherence in both genders ([beta]-coefficient >0, P < 0.001). In addition, 1 unit increase in PAC score was associated with 7.1-7.8% increase in the likelihood of high MeD adherence (P < 0.001). CONCLUSIONS: The intake of flavonoids and lignans in an European Union population was calculated using harmonized European Union FCT data. In addition, a holistic approach in dietary analysis of polyphenol intake was proposed. European Journal of Clinical Nutrition (2016) 70, 338-345; doi: 10.1038/ejcn.2015.178; published online 4 November 2015, INTRODUCTION According to a crude chemical definition, polyphenols are secondary metabolites of plants and are generally involved in the defense against ultraviolet radiation or aggression by pathogens. (1) Dietary polyphenols [...]
Published: 2016
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9. Methylation-based markers of aging and lifestyle-related factors and risk of breast cancer: a pooled analysis of four prospective studies

Author: Dugue, P-A, Bodelon, C, Chung, FF, Brewer, HR, Ambatipudi, S, Sampson, JN, Cuenin, C, Chajes, V, Romieu, I, Fiorito, G, Sacerdote, C, Krogh, V, Panico, S, Tumino, R, Vineis, P, Polidoro, S, Baglietto, L, English, D, Severi, G, Giles, GG, Milne, RL, Herceg, Z, Garcia-Closas, M, Flanagan, JM, Southey, MC, Dugue, P-A, Bodelon, C, Chung, FF, Brewer, HR, Ambatipudi, S, Sampson, JN, Cuenin, C, Chajes, V, Romieu, I, Fiorito, G, Sacerdote, C, Krogh, V, Panico, S, Tumino, R, Vineis, P, Polidoro, S, Baglietto, L, English, D, Severi, G, Giles, GG, Milne, RL, Herceg, Z, Garcia-Closas, M, Flanagan, JM, and Southey, MC
Abstract: BACKGROUND: DNA methylation in blood may reflect adverse exposures accumulated over the lifetime and could therefore provide potential improvements in the prediction of cancer risk. A substantial body of research has shown associations between epigenetic aging and risk of disease, including cancer. Here we aimed to study epigenetic measures of aging and lifestyle-related factors in association with risk of breast cancer. METHODS: Using data from four prospective case-control studies nested in three cohorts of European ancestry participants, including a total of 1,655 breast cancer cases, we calculated three methylation-based measures of lifestyle factors (body mass index [BMI], tobacco smoking and alcohol consumption) and seven measures of epigenetic aging (Horvath-based, Hannum-based, PhenoAge and GrimAge). All measures were regression-adjusted for their respective risk factors and expressed per standard deviation (SD). Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional or unconditional logistic regression and pooled using fixed-effects meta-analysis. Subgroup analyses were conducted by age at blood draw, time from blood sample to diagnosis, oestrogen receptor-positivity status and tumour stage. RESULTS: None of the measures of epigenetic aging were associated with risk of breast cancer in the pooled analysis: Horvath 'age acceleration' (AA): OR per SD = 1.02, 95%CI: 0.95-1.10; AA-Hannum: OR = 1.03, 95%CI:0.95-1.12; PhenoAge: OR = 1.01, 95%CI: 0.94-1.09 and GrimAge: OR = 1.03, 95%CI: 0.94-1.12, in models adjusting for white blood cell proportions, body mass index, smoking and alcohol consumption. The BMI-adjusted predictor of BMI was associated with breast cancer risk, OR per SD = 1.09, 95%CI: 1.01-1.17. The results for the alcohol and smoking methylation-based predictors were consistent with a null association. Risk did not appear to substantially vary by age at blood draw, time to diagnosis or tumour characteristics. CONCLUSION
Published: 2022

10. Epigenetic mechanisms of lung carcinogenesis involve differentially methylated CpG sites beyond those associated with smoking

Author: Petrovic, D, Bodinier, B, Dagnino, S, Whitaker, M, Karimi, M, Campanella, G, Haugdahl Nost, T, Polidoro, S, Palli, D, Krogh, V, Tumino, R, Sacerdote, C, Panico, S, Lund, E, Dugue, P-A, Giles, GG, Severi, G, Southey, M, Vineis, P, Stringhini, S, Bochud, M, Sandanger, TM, Vermeulen, RCH, Guida, F, Chadeau-Hyam, M, Petrovic, D, Bodinier, B, Dagnino, S, Whitaker, M, Karimi, M, Campanella, G, Haugdahl Nost, T, Polidoro, S, Palli, D, Krogh, V, Tumino, R, Sacerdote, C, Panico, S, Lund, E, Dugue, P-A, Giles, GG, Severi, G, Southey, M, Vineis, P, Stringhini, S, Bochud, M, Sandanger, TM, Vermeulen, RCH, Guida, F, and Chadeau-Hyam, M
Abstract: Smoking-related epigenetic changes have been linked to lung cancer, but the contribution of epigenetic alterations unrelated to smoking remains unclear. We sought for a sparse set of CpG sites predicting lung cancer and explored the role of smoking in these associations. We analysed CpGs in relation to lung cancer in participants from two nested case-control studies, using (LASSO)-penalised regression. We accounted for the effects of smoking using known smoking-related CpGs, and through conditional-independence network. We identified 29 CpGs (8 smoking-related, 21 smoking-unrelated) associated with lung cancer. Models additionally adjusted for Comprehensive Smoking Index-(CSI) selected 1 smoking-related and 49 smoking-unrelated CpGs. Selected CpGs yielded excellent discriminatory performances, outperforming information provided by CSI only. Of the 8 selected smoking-related CpGs, two captured lung cancer-relevant effects of smoking that were missed by CSI. Further, the 50 CpGs identified in the CSI-adjusted model complementarily explained lung cancer risk. These markers may provide further insight into lung cancer carcinogenesis and help improving early identification of high-risk patients.
Published: 2022

11. DNA methylation signature of chronic low-grade inflammation and its role in cardio-respiratory diseases

Author: Wielscher, M. (Matthias), Mandaviya, P. R. (Pooja R.), Kuehnel, B. (Brigitte), Joehanes, R. (Roby), Mustafa, R. (Rima), Robinson, O. (Oliver), Zhang, Y. (Yan), Bodinier, B. (Barbara), Walton, E. (Esther), Mishra, P. P. (Pashupati P.), Schlosser, P. (Pascal), Wilson, R. (Rory), Tsai, P.-C. (Pei-Chien), Palaniswamy, S. (Saranya), Marioni, R. E. (Riccardo E.), Fiorito, G. (Giovanni), Cugliari, G. (Giovanni), Karhunen, V. (Ville), Ghanbari, M. (Mohsen), Psaty, B. M. (Bruce M.), Loh, M. (Marie), Bis, J. C. (Joshua C.), Lehne, B. (Benjamin), Sotoodehnia, N. (Nona), Deary, I. J. (Ian J.), Chadeau-Hyam, M. (Marc), Brody, J. A. (Jennifer A.), Cardona, A. (Alexia), Selvin, E. (Elizabeth), Smith, A. K. (Alicia K.), Miller, A. H. (Andrew H.), Torres, M. A. (Mylin A.), Marouli, E. (Eirini), Gao, X. (Xin), van Meurs, J. B. (Joyce B. J.), Graf-Schindler, J. (Johanna), Rathmann, W. (Wolfgang), Koenig, W. (Wolfgang), Peters, A. (Annette), Weninger, W. (Wolfgang), Farlik, M. (Matthias), Zhang, T. (Tao), Chen, W. (Wei), Xia, Y. (Yujing), Teumer, A. (Alexander), Nauck, M. (Matthias), Grabe, H. J. (Hans J.), Doerr, M. (Macus), Lehtimaki, T. (Terho), Guan, W. (Weihua), Milani, L. (Lili), Tanaka, T. (Toshiko), Fisher, K. (Krista), Waite, L. L. (Lindsay L.), Kasela, S. (Silva), Vineis, P. (Paolo), Verweij, N. (Niek), van der Harst, P. (Pim), Iacoviello, L. (Licia), Sacerdote, C. (Carlotta), Panico, S. (Salvatore), Krogh, V. (Vittorio), Tumino, R. (Rosario), Tzala, E. (Evangelia), Matullo, G. (Giuseppe), Hurme, M. A. (Mikko A.), Raitakari, O. T. (Olli T.), Colicino, E. (Elena), Baccarelli, A. A. (Andrea A.), Kahonen, M. (Mika), Herzig, K.-H. (Karl-Heinz), Li, S. (Shengxu), BIOS consortium, Conneely, K. N. (Karen N.), Kooner, J. S. (Jaspal S.), Kottgen, A. (Anna), Heijmans, B. T. (Bastiaan T.), Deloukas, P. (Panos), Relton, C. (Caroline), Ong, K. K. (Ken K.), Bell, J. T. (Jordana T.), Boerwinkle, E. (Eric), Elliott, P. (Paul), Brenner, H. (Hermann), Beekman, M. (Marian), Levy, D. (Daniel), Waldenberger, M. (Melanie), Chambers, J. C. (John C.), Dehghan, A. (Abbas), Järvelin, M.-R. (Marjo-Riitta), Wielscher, M. (Matthias), Mandaviya, P. R. (Pooja R.), Kuehnel, B. (Brigitte), Joehanes, R. (Roby), Mustafa, R. (Rima), Robinson, O. (Oliver), Zhang, Y. (Yan), Bodinier, B. (Barbara), Walton, E. (Esther), Mishra, P. P. (Pashupati P.), Schlosser, P. (Pascal), Wilson, R. (Rory), Tsai, P.-C. (Pei-Chien), Palaniswamy, S. (Saranya), Marioni, R. E. (Riccardo E.), Fiorito, G. (Giovanni), Cugliari, G. (Giovanni), Karhunen, V. (Ville), Ghanbari, M. (Mohsen), Psaty, B. M. (Bruce M.), Loh, M. (Marie), Bis, J. C. (Joshua C.), Lehne, B. (Benjamin), Sotoodehnia, N. (Nona), Deary, I. J. (Ian J.), Chadeau-Hyam, M. (Marc), Brody, J. A. (Jennifer A.), Cardona, A. (Alexia), Selvin, E. (Elizabeth), Smith, A. K. (Alicia K.), Miller, A. H. (Andrew H.), Torres, M. A. (Mylin A.), Marouli, E. (Eirini), Gao, X. (Xin), van Meurs, J. B. (Joyce B. J.), Graf-Schindler, J. (Johanna), Rathmann, W. (Wolfgang), Koenig, W. (Wolfgang), Peters, A. (Annette), Weninger, W. (Wolfgang), Farlik, M. (Matthias), Zhang, T. (Tao), Chen, W. (Wei), Xia, Y. (Yujing), Teumer, A. (Alexander), Nauck, M. (Matthias), Grabe, H. J. (Hans J.), Doerr, M. (Macus), Lehtimaki, T. (Terho), Guan, W. (Weihua), Milani, L. (Lili), Tanaka, T. (Toshiko), Fisher, K. (Krista), Waite, L. L. (Lindsay L.), Kasela, S. (Silva), Vineis, P. (Paolo), Verweij, N. (Niek), van der Harst, P. (Pim), Iacoviello, L. (Licia), Sacerdote, C. (Carlotta), Panico, S. (Salvatore), Krogh, V. (Vittorio), Tumino, R. (Rosario), Tzala, E. (Evangelia), Matullo, G. (Giuseppe), Hurme, M. A. (Mikko A.), Raitakari, O. T. (Olli T.), Colicino, E. (Elena), Baccarelli, A. A. (Andrea A.), Kahonen, M. (Mika), Herzig, K.-H. (Karl-Heinz), Li, S. (Shengxu), BIOS consortium, Conneely, K. N. (Karen N.), Kooner, J. S. (Jaspal S.), Kottgen, A. (Anna), Heijmans, B. T. (Bastiaan T.), Deloukas, P. (Panos), Relton, C. (Caroline), Ong, K. K. (Ken K.), Bell, J. T. (Jordana T.), Boerwinkle, E. (Eric), Elliott, P. (Paul), Brenner, H. (Hermann), Beekman, M. (Marian), Levy, D. (Daniel), Waldenberger, M. (Melanie), Chambers, J. C. (John C.), Dehghan, A. (Abbas), and Järvelin, M.-R. (Marjo-Riitta)
Abstract: We performed a multi-ethnic Epigenome Wide Association study on 22,774 individuals to describe the DNA methylation signature of chronic low-grade inflammation as measured by C-Reactive protein (CRP). We find 1,511 independent differentially methylated loci associated with CRP. These CpG sites show correlation structures across chromosomes, and are primarily situated in euchromatin, depleted in CpG islands. These genomic loci are predominantly situated in transcription factor binding sites and genomic enhancer regions. Mendelian randomization analysis suggests altered CpG methylation is a consequence of increased blood CRP levels. Mediation analysis reveals obesity and smoking as important underlying driving factors for changed CpG methylation. Finally, we find that an activated CpG signature significantly increases the risk for cardiometabolic diseases and COPD.
Published: 2022

12. Milk intake and incident stroke and CHD in populations of European descent: A Mendelian randomisation study

Author: Cardiovasculaire Epi Team 1, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Circulatory Health, Public Health Practice, Public Health Epidemiologie, Vissers, L. E.T., Sluijs, I., Burgess, S., Forouhi, N. G., Freisling, H., Imamura, F., Nilsson, T. K., Renström, F., Weiderpass, E., Aleksandrova, K., Dahm, C. C., Perez-Cornago, A., Schulze, M. B., Tong, T. Y.N., Aune, D., Bonet, C., Boeing, H., Chirlaque, M. D., Conchi, M. I., Imaz, L., Jäger, S., Krogh, V., Kyrø, C., Masala, G., Melander, O., Overvad, K., Panico, S., Sánches, M. J., Sonestedt, E., Tjønneland, A., Tzoulaki, I., Verschuren, W. M.M., Riboli, E., Wareham, N. J., Danesh, J., Butterworth, A. S., Van Der Schouw, Y. T., Cardiovasculaire Epi Team 1, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Circulatory Health, Public Health Practice, Public Health Epidemiologie, Vissers, L. E.T., Sluijs, I., Burgess, S., Forouhi, N. G., Freisling, H., Imamura, F., Nilsson, T. K., Renström, F., Weiderpass, E., Aleksandrova, K., Dahm, C. C., Perez-Cornago, A., Schulze, M. B., Tong, T. Y.N., Aune, D., Bonet, C., Boeing, H., Chirlaque, M. D., Conchi, M. I., Imaz, L., Jäger, S., Krogh, V., Kyrø, C., Masala, G., Melander, O., Overvad, K., Panico, S., Sánches, M. J., Sonestedt, E., Tjønneland, A., Tzoulaki, I., Verschuren, W. M.M., Riboli, E., Wareham, N. J., Danesh, J., Butterworth, A. S., and Van Der Schouw, Y. T.
Published: 2022

13. Cohort Profile: The transition from childhood to adolescence in European children–how I.Family extends the IDEFICS cohort

Author: Ahrens, W, Siani, A, Adan, R, De Henauw, S, Eiben, G, Gwozdz, W, Hebestreit, A, Hunsberger, M, Kaprio, J, Krogh, V, Lissner, L, Molnár, D, Moreno, L A, Page, A, Picó, C, Reisch, L, Smith, R M, Tornaritis, M, Veidebaum, T, Williams, G, Pohlabeln, H, and Pigeot, I
Published: 2017
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14. Body size at different ages and risk of six cancers: a Mendelian randomization and prospective cohort study

Author: Mariosa, D, Smith-Byrne, K, Richardson, TG, Ferrari, P, Gunter, MJ, Papadimitriou, N, Murphy, N, Christakoudi, S, Tsilidis, KK, Riboli, E, Muller, D, Purdue, MP, Chanock, SJ, Hung, RJ, Amos, CI, O'Mara, TA, Amiano, P, Pasanisi, F, Rodriguez-Barranco, M, Krogh, V, Tjønneland, A, Halkjær, J, Perez-Cornago, A, Chirlaque, M-D, Skeie, G, Rylander, C, Borch, KB, Aune, D, Heath, AK, Ward, HA, Schulze, M, Bonet, C, Weiderpass, E, Smith, GD, Brennan, P, Johansson, M, Mariosa, Daniela, Smith-Byrne, Karl, Richardson, Tom G, Ferrari, Pietro, Gunter, Marc J, Papadimitriou, Niko, Murphy, Neil, Christakoudi, Sofia, Tsilidis, Konstantinos K, Riboli, Elio, Muller, David, Purdue, Mark P, Chanock, Stephen J, Hung, Rayjean J, Amos, Christopher I, O'Mara, Tracy A, Amiano, Pilar, Pasanisi, Fabrizio, Rodriguez-Barranco, Miguel, Krogh, Vittorio, Tjønneland, Anne, Halkjær, Jytte, Perez-Cornago, Aurora, Chirlaque, María-Dolore, Skeie, Guri, Rylander, Charlotta, Borch, Kristin Benjaminsen, Aune, Dagfinn, Heath, Alicia K, Ward, Heather A, Schulze, Matthia, Bonet, Catalina, Weiderpass, Elisabete, Smith, George Davey, Brennan, Paul, and Johansson, Mattias
Subjects: Adult, SUSCEPTIBILITY LOCI, Epidemiology, OVARIAN-CANCER, Body Mass Index, 1117 Public Health and Health Services, POOLED ANALYSIS, Cohort Studies, MASS INDEX, Neoplasms, Body Size, Humans, Obesity, Prospective Studies, Genetics & Heredity, LIFE-COURSE, 0604 Genetics, Science & Technology, IDENTIFICATION, ENDOMETRIAL CANCER, Mendelian Randomization Analysis, Oncology, ADIPOSITY, Mathematical & Computational Biology, Life Sciences & Biomedicine, ANTHROPOMETRIC FACTORS, Genome-Wide Association Study
Abstract: It is unclear if body weight in early life affects cancer risk independently of adult body weight. To investigate this question for six obesity-related cancers, we performed univariable and multivariable analyses using i) Mendelian randomization (MR) analysis and ii) longitudinal analyses in prospective cohorts. Both the MR and longitudinal analyses indicated that larger body size at age 10 was associated with higher risk of endometrial (ORMR=1.61, 95%CI = 1.23-2.11) and kidney cancer (ORMR=1.40, 95%CI = 1.09-1.80). These associations were attenuated after accounting for adult body size in both the MR and cohort analyses. Early life BMI was not consistently associated with the other investigated cancers. The lack of clear independent risk associations suggests that early life BMI influences endometrial and kidney cancer risk mainly through pathways that are common with adult BMI.
Published: 2022

15. Meat Intake and Bladder Cancer in a Prospective Study: A Role for Heterocyclic Aromatic Amines?

Author: Lumbreras, B., Garte, S., Overvad, K., Tjonneland, A., Clavel-Chapelon, F., Linseisen, J. P., Boeing, H., Trichopoulou, A., Palli, D., Peluso, M., Krogh, V., Tumino, R., Panico, S., Bueno-De-Mesquita, H. B., Peeters, P. H., Lund, E., Martinez, C., Dorronsoro, M., Barricarte, A., Chirlaque, M.-D., Quiros, J. R., Berglund, G., Hallmans, G., Day, N. E., Key, T. J., Saracci, R., Kaaks, R., Malaveille, C., Ferrari, P., Boffetta, P., Norat, T., Riboli, E., Gonzalez, C. A., and Vineis, P.
Published: 2008
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16. Milk intake and incident stroke and coronary heart disease in populations of European descent: A Mendelian Randomization study

Author: Vissers, L.E.T., Sluijs, I., Burgess, S., Forouhi, N.G., Freisling, H., Imamura, F., Nilsson, Torbjörn K., Renström, Frida, Weiderpass, E., Aleksandrova, K., Dahm, C.C., Perez-Cornago, A., Schulze, M.B., Tong, T.Y.N., Aune, D., Bonet, C., Boer, J.M.A., Boeing, H., Chirlaque, M.D., Conchi, M.I., Imaz, L., Jäger, S., Krogh, V., Kyrø, C., Masala, G., Melander, O., Overvad, K., Panico, S., Sánches, M.J., Sonestedt, E., Tjønneland, A., Tzoulaki, I., Verschuren, W.M.M., Riboli, E., Wareham, N.J., Danesh, J., Butterworth, A.S., and Van Der Schouw, Y.T.
Subjects: Näringslära, Nutrition and Dietetics, CHD, Milk, Mendelian Randomization, dairy, stroke
Abstract: Higher milk intake has been associated with a lower stroke risk, but not with risk of coronary heart disease (CHD). Residual confounding or reverse causation cannot be excluded. Therefore, we estimated the causal association of milk consumption with stroke and CHD risk through instrumental variable (IV) and gene-outcome analyses. IV analysis included 29,328 participants (4,611 stroke; 9,828 CHD) of the EPIC-CVD (8 European countries) and EPIC-NL case-cohort studies. rs4988235, a lactase persistence (LP) single nucleotide polymorphism which enables digestion of lactose in adulthood was used as genetic instrument. Intake of milk was first regressed on rs4988235 in a linear regression model. Next, associations of genetically predicted milk consumption with stroke and CHD were estimated using Prentice-weighted Cox regression. Gene-outcome analysis included 777,024 participants (50,804 cases) from MEGASTROKE (including EPIC-CVD), UK Biobank and EPIC-NL for stroke, and 483,966 participants (61,612 cases) from CARDIoGRAM, UK Biobank and EPIC-CVD and EPIC-NL for CHD. In IV analyses, each additional LP allele was associated with a higher intake of milk in EPIC-CVD (β=13.7 g/day; 95%CI: 8.4-19.1) and EPIC-NL (36.8 g/day; 20.0-53.5). Genetically predicted milk intake was not associated with stroke (HR per 25 g/day 1.05; 95%CI: 0.94-1.16) or CHD (1.02; 0.96-1.08). In gene-outcome analyses, there was no association of rs4988235 with risk of stroke (odds ratios 1.02; 0.99-1.05) or CHD (0.99; 0.95-1.03). Current Mendelian Randomization analysis does not provide evidence for a causal inverse relationship between milk consumption and stroke or CHD risk. MEGASTROKE
Published: 2021

17. Country-specific dietary patterns and associations with socioeconomic status in European children: the IDEFICS study

Author: Fernandez-Alvira, J.M., Bammann, K., Pala, V., Krogh, V., Barba, G., Eiben, G., Hebestreit, A., Veidebaum, T., Reisch, L., Tornaritis, M., Kovacs, E., Huybrechts, I., and Moreno, L.A.
Subjects: Social economics -- Research, Medical research, Medicine, Experimental, Sociological research, Children -- Health aspects, Diet -- Health aspects -- Demographic aspects, Food/cooking/nutrition, Health
Abstract: BACKGROUND/OBJECTIVES: Children from lower socioeconomic status (SES) may be at higher risk of unhealthy eating. We described country-specific dietary patterns among children aged 2-9 years from eight European countries participating in the IDEFICS study and assessed the association of dietary patterns with an additive SES indicator. SUBJECTS/METHODS: Children aged 2-9 years from eight European countries were recruited in 2007-2008. Principal component analysis was applied to identify dietary country-specific patterns. Linear regression analyses were applied to assess their association with SES. RESULTS: Two to four dietary patterns were identified in the participating regions. The existence of a 'processed' pattern was found in the eight regions. Also, a 'healthy' pattern was identified in seven of the eight regions. In addition, region-specific patterns were identified, reflecting the existing gastronomic and cultural differences in Europe. The 'processed' pattern was significantly inversely associated with the SES additive indicator in all countries except Sweden, whereas the 'healthy' pattern was positively associated with SES in the Belgian, Estonian, German and Hungarian regions, but was not significant in the Italian, Spanish and Swedish regions. CONCLUSIONS: A 'processed' pattern and a 'healthy' pattern were found in most of the participating countries in the IDEFICS study, with comparable food item profiles. The results showed a strong inverse association of SES with the 'processed' pattern, suggesting that children of parents with lower SES may be at higher risk of unhealthy eating. Therefore, special focus should be given to parents and their children from lower SES levels when developing healthy eating promotion strategies. European Journal of Clinical Nutrition (2014) 68, 811-821;doi:10.1038/ejcn.2014.78; published online 14 May 2014, INTRODUCTION Social inequalities in health are present from childhood until adult life; socioeconomic status (SES) differences in the risk of morbidity and mortality have been well documented. (1) The burden [...]
Published: 2014
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18. Associations between energy intake, daily food intake and energy density of foods and BMI z-score in 2–9-year-old European children

Author: Hebestreit, A., Börnhorst, C., Barba, G., Siani, A., Huybrechts, I., Tognon, G., Eiben, G., Moreno, L. A., Fernández Alvira, J. M., Loit, H. M., Kovacs, E., Tornaritis, M., and Krogh, V.
Published: 2014
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19. Milk intake and incident stroke and CHD in populations of European descent: a Mendelian randomisation study

Author: Vissers, L. E. T., primary, Sluijs, I., additional, Burgess, S., additional, Forouhi, N. G., additional, Freisling, H., additional, Imamura, F., additional, Nilsson, T. K., additional, Renström, F., additional, Weiderpass, E., additional, Aleksandrova, K., additional, Dahm, C. C., additional, Perez-Cornago, A., additional, Schulze, M. B., additional, Tong, T. Y. N., additional, Aune, D., additional, Bonet, C., additional, Boer, J. M. A., additional, Boeing, H., additional, Chirlaque, M. D., additional, Conchi, M. I., additional, Imaz, L., additional, Jäger, S., additional, Krogh, V., additional, Kyrø, C., additional, Masala, G., additional, Melander, O., additional, Overvad, K., additional, Panico, S., additional, Sánches, M. J., additional, Sonestedt, E., additional, Tjønneland, A., additional, Tzoulaki, I., additional, Verschuren, W. M. M., additional, Riboli, E., additional, Wareham, N. J., additional, Danesh, J., additional, Butterworth, A. S., additional, and van der Schouw, Y. T., additional
Published: 2021
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20. Dietary glycemic index and glycemic load and risk of colorectal cancer: results from the EPIC-Italy study

Author: Sieri, S., Krogh, V., Agnoli, C., Ricceri, F., Palli, D., Masala, G., Panico, S., Mattiello, A., Tumino, R., Giurdanella, M. C., Brighenti, F., Scazzina, F., Vineis, P., and Sacerdote, C.
Published: 2015
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21. Dietary patterns and longitudinal change in body mass in European children: a follow-up study on the IDEFICS multicenter cohort

Author: Pala, V., Lissner, L., Hebestreit, A., Lanfer, A., Sieri, S., Siani, A., Huybrechts, I., Kambek, L., Molnar, D., Tornaritis, M., Moreno, L., Ahrens, W., and Krogh, V.
Subjects: Obesity in children -- Prevention, Food/cooking/nutrition, Health
Abstract: BACKGROUND/OBJECTIVES: Longitudinal studies investigating dietary patterns (DPs) and their association with childhood overweight/obesity are lacking in Europe. We identified DPs and investigated their association with overweight/obesity and changes in body mass index (BMI) in a cohort of European children. SUBJECTS/METHODS: Children aged 2-10 from eight European countries were recruited in 2007-2008. Food frequency questionnaires were collected from 14989 children. BMI and BMI z-scores were derived from height and weight and were used to identify overweight/obese children. After 2 years (mean), anthropometric measurements were repeated in 9427 children. Principal component analysis was used to identify DPs. Simplified DPs (SDPs) were derived from DPs. Adjusted odds ratios (ORs) for overweight/obesity with increasing DP intake were estimated using multilevel logistic regression. Associations of BMI change with DP and SDP were assessed by multilevel mixed regression. Models were adjusted for baseline BMI, age, sex, physical activity and family income. RESULTS: Four DPs were identified that explained 25% of food intake variance: snacking, sweet and fat, vegetables and wholemeal, and protein and water. After 2 years, 849(9%) children became overweight/obese. Children in the highest vegetables and wholemeal tertile had lower risk of becoming overweight/obese (OR: 0.69, 95% confidence intervals (CIs): 0.54-0.88). Children in the highest SDP tertile of vegetables and wholemeal had similarly lower risk of becoming overweight/obese (OR: 0.64, 95% CIs: 0.51-0.82), and their BMI increased by 0.7 kg/[m.sup.2] over the study period-- significantly less than the increase in the lowest tertile (0.84 kg/[m.sup.2]). CONCLUSIONS: Our findings suggest that promoting a diet rich in vegetables and wholemeal cereals may counteract overweight/obesity in children. European Journal of Clinical Nutrition (2013) 67, 1042-1049; doi: 10.1038/ejcn.2013.145; published online 14 August 2013 Keywords: dietary patterns; simplified dietary patterns; children; body mass index; overweight; cohort study, INTRODUCTION Childhood overweight and obesity increased at an alarming rate in Europe and elsewhere up to about 2000, but now it appears to have levelled off. (1) However, childhood overweight [...]
Published: 2013
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22. Clustering of multiple lifestyle behaviours and its association to cardiovascular risk factors in children: the IDEFICS study

Author: Bel-Serrat, S., Mouratidou, T., Santaliestra-Pasias, A.M., Iacoviell, L., Kourides, Y.A., Marild, S., Molnar, D., Reisch, L., Siani, A., Stomfai, S., Vanaelst, B., Veidebaum, T., Pigeot, I., Ahrens, W., Krogh, V., and Moreno, L.A.
Subjects: Life style -- Research, Children -- Health aspects, Cardiovascular diseases -- Physiological aspects -- Risk factors, Food/cooking/nutrition, Health
Abstract: BACKGROUND/OBJECTIVES: Individual lifestyle behaviours have independently been associated with cardiovascular diseases (CVD) risk factors in children. This study aimed to identify clustered lifestyle behaviours (dietary, physical activity (PA) and sedentary indicators) and to examine their association with CVD risk factors in children aged 2-9 years. SUBJECTS/METHODS: Participants included 4619 children (51.6% boys) from eight European countries participating in the IDEFICS cross-sectional baseline survey (2007-2008). Insulin resistance, total cholesterol/high-density lipoprotein cholesterol ratio, triglycerides, sum of two skinfolds and systolic blood pressure (SBP) z-scores were summed to compute a CVD risk score. Cluster analyses stratified by sex and age groups (2 to < 6 years; 6-9 years) were performed using parental-reported data on fruit, vegetables and sugar-sweetened beverages (SSB) consumption, PA performance and television video/DVD viewing. RESULTS: Five clusters were identified. Associations between CVD risk factors and score, and clusters were obtained by multiple linear regression using cluster 5 ('low beverages consumption and low sedentary') as the reference cluster. SBP was positively associated with clusters 1 ('physically active'; β = 1.34;95% confidence interval (CI): 0.02, 2.67), 2 ('sedentary'; β = 1.84; 95% CI: 0.57, 3.11), 3 ('physically active and sedentary'; β = 1.45;95% CI: 0.15, 2.75) and 4 ('healthy diet'; β = 1.83;95% CI: 0.50, 3.17) in older boys. A positive association was observed between CVD risk score and clusters 2 (b = 0.60;95% CI: 0.20, 1.01), 3 (b = 0.55;95% CI: 0.14, 0.97) and 4 (β = 0.60, 95% CI: 0.18, 1.02) in older boys. CONCLUSIONS: Low television/video/DVD viewing levels and low SSB consumption may result in a healthier CVD profile rather than having a diet rich in fruits and vegetables or being physically active in (pre-)school children. European Journal of Clinical Nutrition (2013) 67, 848-854; doi:10.1038/ejcn.2013.84; published online 1 May 2013 Keywords: cardiovascular diseases; lifestyle; diet; exercise; sedentary lifestyle; child, INTRODUCTION Increased risk of CVD is characterized by a cluster of metabolic abnormalities, such as abdominal obesity, atherogenic dyslipemia, hypertension, insulin resistance and glucose intolerance. (1) CVD remains the leading [...]
Published: 2013
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23. Alcohol dehydrogenase and aldehyde dehydrogenase gene polymorphisms, alcohol intake and the risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition study

Author: Ferrari, P, McKay, J D, Jenab, M, Brennan, P, Canzian, F, Vogel, U, Tjønneland, A, Overvad, K, Tolstrup, J S, Boutron-Ruault, M-C, Clavel-Chapelon, F, Morois, S, Kaaks, R, Boeing, H, Bergmann, M, Trichopoulou, A, Katsoulis, M, Trichopoulos, D, Krogh, V, Panico, S, Sacerdote, C, Palli, D, Tumino, R, Peeters, P H, van Gils, C H, Bueno-de-Mesquita, B, Vrieling, A, Lund, E, Hjartåker, A, Agudo, A, Suarez, L R, Arriola, L, Chirlaque, M-D, Ardanaz, E, Sánchez, M-J, Manjer, J, Lindkvist, B, Hallmans, G, Palmqvist, R, Allen, N, Key, T, Khaw, K-T, Slimani, N, Rinaldi, S, Romieu, I, Boffetta, P, Romaguera, D, Norat, T, and Riboli, E
Published: 2012
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24. Reducing socio-economic inequalities in all-cause mortality: A counterfactual mediation approach.

Author: Laine J.E., Baltar V.T., Stringhini S., Gandini M., Chadeau-Hyam M., Kivimaki M., Severi G., Perduca V., Hodge A.M., Dugue P.-A., Giles G.G., Milne R.L., Barros H., Sacerdote C., Krogh V., Panico S., Tumino R., Goldberg M., Zins M., Delpierre C., Laine J.E., Baltar V.T., Stringhini S., Gandini M., Chadeau-Hyam M., Kivimaki M., Severi G., Perduca V., Hodge A.M., Dugue P.-A., Giles G.G., Milne R.L., Barros H., Sacerdote C., Krogh V., Panico S., Tumino R., Goldberg M., Zins M., and Delpierre C.
Abstract: Background: Socio-economic inequalities in mortality are well established, yet the contribution of intermediate risk factors that may underlie these relationships remains unclear. We evaluated the role of multiple modifiable intermediate risk factors underlying socio- economic-associated mortality and quantified the potential impact of reducing early allcause mortality by hypothetically altering socio-economic risk factors. Method(s): Data were from seven cohort studies participating in the LIFEPATH Consortium (total n 179 090). Using both socio-economic position (SEP) (based on occupation) and education, we estimated the natural direct effect on all-cause mortality and the natural indirect effect via the joint mediating role of smoking, alcohol intake, dietary patterns, physical activity, body mass index, hypertension, diabetes and coronary artery disease. Hazard ratios (HRs) were estimated, using counterfactual natural effect models under different hypothetical actions of either lower or higher SEP or education. Result(s): Lower SEP and education were associated with an increase in all-cause mortality within an average follow-up time of 17.5 years. Mortality was reduced via modelled hypothetical actions of increasing SEP or education. Through higher education, the HR was 0.85 [95% confidence interval (CI) 0.84, 0.86] for women and 0.71 (95% CI 0.70, 0.74) for men, compared with lower education. In addition, 34% and 38% of the effect was jointly mediated for women and men, respectively. The benefits from altering SEP were slightly more modest. Conclusion(s): These observational findings support policies to reduce mortality both through improving socio-economic circumstances and increasing education, and by altering intermediaries, such as lifestyle behaviours and morbidities.Copyright © The Author(s) 2019.
Published: 2021

25. Body size and weight change over adulthood and risk of breast cancer by menopausal and hormone receptor status: a pooled analysis of 20 prospective cohort studies.

Author: Sinha R., Rohan T.E., Sawada N., Schouten L.J., Stolzenberg-Solomon R.Z., Teras L.R., Tsugane S., Visvanathan K., Weiderpass E., White K.K., Willett W.C., Wolk A., Zeleniuch-Jacquotte A., Smith-Warner S.A., van den Brandt P.A., Ziegler R.G., Wang M., Hou T., Li R., Adami H.-O., Agnoli C., Bernstein L., Buring J.E., Chen Y., Connor A.E., Eliassen A.H., Genkinger J.M., Gierach G., Giles G.G., Goodman G.G., Hakansson N., Krogh V., Le Marchand L., Lee I.-M., Liao L.M., Martinez M.E., Miller A.B., Milne R.L., Neuhouser M.L., Patel A.V., Prizment A., Robien K., Sinha R., Rohan T.E., Sawada N., Schouten L.J., Stolzenberg-Solomon R.Z., Teras L.R., Tsugane S., Visvanathan K., Weiderpass E., White K.K., Willett W.C., Wolk A., Zeleniuch-Jacquotte A., Smith-Warner S.A., van den Brandt P.A., Ziegler R.G., Wang M., Hou T., Li R., Adami H.-O., Agnoli C., Bernstein L., Buring J.E., Chen Y., Connor A.E., Eliassen A.H., Genkinger J.M., Gierach G., Giles G.G., Goodman G.G., Hakansson N., Krogh V., Le Marchand L., Lee I.-M., Liao L.M., Martinez M.E., Miller A.B., Milne R.L., Neuhouser M.L., Patel A.V., Prizment A., and Robien K.
Abstract: Associations between anthropometric factors and breast cancer (BC) risk have varied inconsistently by estrogen and/or progesterone receptor (ER/PR) status. Associations between prediagnostic anthropometric factors and risk of premenopausal and postmenopausal BC overall and ER/PR status subtypes were investigated in a pooled analysis of 20 prospective cohorts, including 36,297 BC cases among 1,061,915 women, using multivariable Cox regression analyses, controlling for reproductive factors, diet and other risk factors. We estimated dose-response relationships and tested for nonlinear associations using restricted cubic splines. Height showed positive, linear associations for premenopausal and postmenopausal BC risk (6-7% RR increase per 5 cm increment), with stronger associations for receptor-positive subtypes. Body mass index (BMI) at cohort baseline was strongly inversely associated with premenopausal BC risk, and strongly positively-and nonlinearly-associated with postmenopausal BC (especially among women who never used hormone replacement therapy). This was primarily observed for receptor-positive subtypes. Early adult BMI (at 18-20 years) showed inverse, linear associations for premenopausal and postmenopausal BC risk (21% and 11% RR decrease per 5 kg/m2, respectively) with stronger associations for receptor-negative subtypes. Adult weight gain since 18-20 years was positively associated with postmenopausal BC risk, stronger for receptor-positive subtypes, and among women who were leaner in early adulthood. Women heavier in early adulthood generally had reduced premenopausal BC risk, independent of later weight gain. Positive associations between height, baseline (adult) BMI, adult weight gain and postmenopausal BC risk were substantially stronger for hormone receptor-positive versus negative subtypes. Premenopausal BC risk was positively associated with height, but inversely with baseline BMI and weight gain (mostly in receptor-positive subtypes). Inverse associ
Published: 2021

26. Dairy foods, calcium, and risk of breast cancer overall and for subtypes defined by estrogen receptor status: a pooled analysis of 21 cohort studies.

Author: Wu Y., Huang R., Wang M., Bernstein L., Bethea T.N., Chen C., Chen Y., Eliassen A.H., Freedman N.D., Gaudet M.M., Gierach G.L., Giles G.G., Krogh V., Larsson S.C., Liao L.M., Mccullough M.L., Miller A.B., Milne R.L., Monroe K.R., Neuhouser M.L., Palmer J.R., Prizment A., Reynolds P., Robien K., Rohan T.E., Sandin S., Sawada N., Sieri S., Sinha R., Stolzenberg-Solomon R.Z., Tsugane S., Van Den Brandt P.A., Visvanathan K., Weiderpass E., Wilkens L.R., Willett W.C., Wolk A., Zeleniuch-Jacquotte A., Ziegler R.G., Smith-Warner S.A., Wu Y., Huang R., Wang M., Bernstein L., Bethea T.N., Chen C., Chen Y., Eliassen A.H., Freedman N.D., Gaudet M.M., Gierach G.L., Giles G.G., Krogh V., Larsson S.C., Liao L.M., Mccullough M.L., Miller A.B., Milne R.L., Monroe K.R., Neuhouser M.L., Palmer J.R., Prizment A., Reynolds P., Robien K., Rohan T.E., Sandin S., Sawada N., Sieri S., Sinha R., Stolzenberg-Solomon R.Z., Tsugane S., Van Den Brandt P.A., Visvanathan K., Weiderpass E., Wilkens L.R., Willett W.C., Wolk A., Zeleniuch-Jacquotte A., Ziegler R.G., and Smith-Warner S.A.
Abstract: Background: Epidemiologic studies examining the relations between dairy product and calcium intakes and breast cancer have been inconclusive, especially for tumor subtypes. Objective(s): To evaluate the associations between intakes of specific dairy products and calcium and risk of breast cancer overall and for subtypes defined by estrogen receptor (ER) status. Method(s): We pooled the individual-level data of over 1 million women who were followed for a maximum of 8-20 years across studies. Associations were evaluated for dairy product and calcium intakes and risk of incident invasive breast cancer overall (n = 37,861 cases) and by subtypes defined by ER status. Study-specific multivariable hazard ratios (HRs) were estimated and then combined using random-effects models. Result(s): Overall, no clear association was observed between the consumption of specific dairy foods, dietary (from foods only) calcium, and total (from foods and supplements) calcium, and risk of overall breast cancer. Although each dairy product showed a null or very weak inverse association with risk of overall breast cancer (P, test for trend >0.05 for all), differences by ER status were suggested for yogurt and cottage/ricotta cheese with associations observed for ER-negative tumors only (pooled HR = 0.90, 95% CI: 0.83, 0.98 comparing >=60 g/d with <1 g/d of yogurt and 0.85, 95% CI: 0.76, 0.95 comparing >=25 g/d with <1 g/d of cottage/ricotta cheese). Dietary calcium intake was only weakly associated with breast cancer risk (pooled HR = 0.98, 95% CI: 0.97, 0.99 per 350 mg/d). Conclusion(s): Our study shows that adult dairy or calcium consumption is unlikely to associate with a higher risk of breast cancer and that higher yogurt and cottage/ricotta cheese intakes were inversely associated with the risk of ER-negative breast cancer, a less hormonally dependent subtype with poor prognosis. Future studies on fermented dairy products, earlier life exposures, ER-negative breast cancer, and differen
Published: 2021

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

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

28. Stochastic epigenetic mutations are associated with risk of breast cancer, lung cancer, and mature b-cell neoplasms.

Author: Gagliardi A., Dugue P.-A., Nost T.H., Southey M.C., Buchanan D.D., Schmidt D.F., Makalic E., Hodge A.M., English D.R., Doo N.W., Hopper J.L., Severi G., Baglietto L., Naccarati A., Tarallo S., Pace L., Krogh V., Palli D., Panico S., Sacerdote C., Tumino R., Lund E., Giles G.G., Pardini B., Sandanger T.M., Milne R.L., Vineis P., Polidoro S., Fiorito G., Gagliardi A., Dugue P.-A., Nost T.H., Southey M.C., Buchanan D.D., Schmidt D.F., Makalic E., Hodge A.M., English D.R., Doo N.W., Hopper J.L., Severi G., Baglietto L., Naccarati A., Tarallo S., Pace L., Krogh V., Palli D., Panico S., Sacerdote C., Tumino R., Lund E., Giles G.G., Pardini B., Sandanger T.M., Milne R.L., Vineis P., Polidoro S., and Fiorito G.
Abstract: Background: Age-related epigenetic dysregulations are associated with several diseases, including cancer. The number of stochastic epigenetic mutations (SEM) has been suggested as a biomarker of life-course accumulation of exposure-related DNA damage; however, the predictive role of SEMs in cancer has seldom been investigated. Method(s): A SEM, at a given CpG site, was defined as an extreme outlier of DNA methylation value distribution across individuals. We investigated the association of the total number of SEMs with the risk of eight cancers in 4,497 case-control pairs nested in three prospective cohorts. Furthermore, we investigated whether SEMs were randomly distributed across the genome or enriched in functional genomic regions. Result(s): In the three-study meta-analysis, the estimated ORs per one-unit increase in log(SEM) from logistic regression models adjusted for age and cancer risk factors were 1.25; 95% confidence interval (CI), 1.11-1.41 for breast cancer, and 1.23; 95% CI, 1.07-1.42 for lung cancer. In the Melbourne Collaborative Cohort Study, the OR for mature B-cell neoplasm was 1.46; 95% CI, 1.25-1.71. Enrichment analyses indicated that SEMs frequently occur in silenced genomic regions and in transcription factor binding sites regulated by EZH2 and SUZ12 (P < 0.0001 and P 1/4 0.0005, respectively): two components of the polycomb repressive complex 2 (PCR2). Finally, we showed that PCR2-specific SEMs are generally more stable over time compared with SEMs occurring in the whole genome. Conclusion(s): The number of SEMs is associated with a higher risk of different cancers in prediagnostic blood samples. Impact: We identified a candidate biomarker for cancer early detection, and we described a carcinogenesis mechanism involving PCR2 complex proteins worthy of further investigations. The authors are very thankful to Dr. Akram Ghantous (IARC, Lyon, France) for the methylation analyses of PEM-Turin study, produced within the Exposomics EC FP7 grant (gran
Published: 2021

29. Dietary Intake of Advanced Glycation End Products (AGEs) and Mortality among Individuals with Colorectal Cancer

Author: Mao, Z, Aglago, EK, Zhao, Z, Schalkwijk, C, Jiao, L, Freisling, H, Weiderpass, E, Hughes, DJ, Eriksen, AK, Tjonneland, A, Severi, G, Rothwell, J, Boutron-Ruault, M-C, Katzke, V, Kaaks, R, Schulze, MB, Birukov, A, Krogh, V, Panico, S, Tumino, R, Ricceri, F, Bueno-de-Mesquita, HB, Vermeulen, RCH, Gram, IT, Skeie, G, Sandanger, TM, Quiros, JR, Crous-Bou, M, Sanchez, M-J, Amiano, P, Chirlaque, M-D, Barricarte Gurrea, A, Manjer, J, Johansson, I, Perez-Cornago, A, Jenab, M, Fedirko, V, Mao, Z, Aglago, EK, Zhao, Z, Schalkwijk, C, Jiao, L, Freisling, H, Weiderpass, E, Hughes, DJ, Eriksen, AK, Tjonneland, A, Severi, G, Rothwell, J, Boutron-Ruault, M-C, Katzke, V, Kaaks, R, Schulze, MB, Birukov, A, Krogh, V, Panico, S, Tumino, R, Ricceri, F, Bueno-de-Mesquita, HB, Vermeulen, RCH, Gram, IT, Skeie, G, Sandanger, TM, Quiros, JR, Crous-Bou, M, Sanchez, M-J, Amiano, P, Chirlaque, M-D, Barricarte Gurrea, A, Manjer, J, Johansson, I, Perez-Cornago, A, Jenab, M, and Fedirko, V
Abstract: Advanced glycation end-products (AGEs) may promote oxidative stress and inflammation and have been linked to multiple chronic diseases, including cancer. However, the association of AGEs with mortality after colorectal cancer (CRC) diagnosis has not been previously investigated. Multivariable Cox proportional hazards models were used to calculate hazard ratios and corresponding 95% confidence intervals for associations between dietary intake of AGEs with CRC-specific and all-cause mortality among 5801 participant cases diagnosed with CRC in the European Prospective Investigation into Cancer and Nutrition study between 1993 and 2013. Dietary intakes of AGEs were estimated using country-specific dietary questionnaires, linked to an AGE database, that accounted for food preparation and processing. During a median of 58 months of follow-up, 2421 cases died (1841 from CRC). Individually or combined, dietary intakes of AGEs were not associated with all-cause and CRC-specific mortality among cases. However, there was a suggestion for a positive association between AGEs and all-cause or CRC-specific mortality among CRC cases without type II diabetes (all-cause, Pinteraction = 0.05) and CRC cases with the longest follow-up between recruitment and cancer diagnosis (CRC-specific, Pinteraction = 0.003; all-cause, Pinteraction = 0.01). Our study suggests that pre-diagnostic dietary intakes of AGEs were not associated with CRC-specific or all-cause mortality among CRC patients. Further investigations using biomarkers of AGEs and stratifying by sex, diabetes status, and timing of exposure to AGEs are warranted.
Published: 2021

30. Dairy foods, calcium, and risk of breast cancer overall and for subtypes defined by estrogen receptor status: a pooled analysis of 21 cohort studies

Author: Wu, Y., Huang, R.Y., Wang, M.L., Bernstein, L., Bethea, T.N., Chen, C., Chen, Y., Eliassen, A.H., Freedman, N.D., Gaudet, M.M., Gierach, G.L., Giles, G.G., Krogh, V., Larsson, S.C., Liao, L.M., McCullough, M.L., Miller, A.B., Milne, R.L., Monroe, K.R., Neuhouser, M.L., Palmer, J.R., Prizment, A., Reynolds, P., Robien, K., Rohan, T.E., Sandin, S., Sawada, N., Sieri, S., Sinha, R., Stolzenberg-Solomon, R.Z., Tsugane, S., van den Brandt, P.A., Visvanathan, K., Weiderpass, E., Wilkens, L.R., Willett, W.C., Wolk, A., Zeleniuch-Jacquotte, A., Ziegler, R.G., Smith-Warner, S.A., Wu, Y., Huang, R.Y., Wang, M.L., Bernstein, L., Bethea, T.N., Chen, C., Chen, Y., Eliassen, A.H., Freedman, N.D., Gaudet, M.M., Gierach, G.L., Giles, G.G., Krogh, V., Larsson, S.C., Liao, L.M., McCullough, M.L., Miller, A.B., Milne, R.L., Monroe, K.R., Neuhouser, M.L., Palmer, J.R., Prizment, A., Reynolds, P., Robien, K., Rohan, T.E., Sandin, S., Sawada, N., Sieri, S., Sinha, R., Stolzenberg-Solomon, R.Z., Tsugane, S., van den Brandt, P.A., Visvanathan, K., Weiderpass, E., Wilkens, L.R., Willett, W.C., Wolk, A., Zeleniuch-Jacquotte, A., Ziegler, R.G., and Smith-Warner, S.A.
Abstract: Background: Epidemiologic studies examining the relations between dairy product and calcium intakes and breast cancer have been inconclusive, especially for tumor subtypes.Objective: To evaluate the associations between intakes of specific dairy products and calcium and risk of breast cancer overall and for subtypes defined by estrogen receptor (ER) status.Method: We pooled the individual-level data of over 1 million women who were followed for a maximum of 8-20 years across studies. Associations were evaluated for dairy product and calcium intakes and risk of incident invasive breast cancer overall (n = 37,861 cases) and by subtypes defined by ER status. Study-specific multivariable hazard ratios (HRs) were estimated and then combined using random-effects models.Results: Overall, no clear association was observed between the consumption of specific dairy foods, dietary (from foods only) calcium, and total (from foods and supplements) calcium, and risk of overall breast cancer. Although each dairy product showed a null or very weak inverse association with risk of overall breast cancer (P, test for trend >0.05 for all), differences by ER status were suggested for yogurt and cottage/ricotta cheese with associations observed for ER-negative tumors only (pooled HR = 0.90, 95% CI: 0.83, 0.98 comparing >= 60 g/d with = 25 g/d withConclusion: Our study shows that adult dairy or calcium consumption is unlikely to associate with a higher risk of breast cancer and that higher yogurt and cottage/ricotta cheese intakes were inversely associated with the risk of ER-negative breast cancer, a less hormonally dependent subtype with poor prognosis. Future studies on fermented dairy products, earlier life exposures, ER-negative breast cancer, and different racial/ethnic populations may further elucidate the relation.
Published: 2021

31. Total dietary antioxidant capacity and lung function in an Italian population: a favorable role in premenopausal/never smoker women

Author: di Giuseppe, R, Arcari, A, Serafini, M, Di Castelnuovo, A, Zito, F, De Curtis, A, Sieri, S, Krogh, V, Pellegrini, N, Schünemann, H J, Donati, M B, de Gaetano, G, and Iacoviello, L
Published: 2012
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32. C reactive protein and its determinants in healthy men and women from European regions at different risk of coronary disease: the IMMIDIET Project

Author: ARCARI, A., ZITO, F., DI CASTELNUOVO, A., DE CURTIS, A., DIRCKX, C., ARNOUT, J., CAPPUCCIO, F.P., VAN DONGEN, M.C.J.M., DE LORGERIL, M., KROGH, V., SIANI, A., DONATI, M.B., DE GAETANO, G., and IACOVIELLO, L.
Published: 2008
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33. Usual energy and macronutrient intakes in 2-9-year-old European children

Author: Börnhorst, C, Huybrechts, I, Hebestreit, A, Krogh, V, De Decker, A, Barba, G, Moreno, L A, Lissner, L, Tornaritis, M, Loit, H-M, Molnár, D, and Pigeot, I
Published: 2014
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34. Adherence to a Mediterranean-like dietary pattern in children from eight European countries. The IDEFICS study

Author: Tognon, G, Moreno, L A, Mouratidou, T, Veidebaum, T, Molnár, D, Russo, P, Siani, A, Akhandaf, Y, Krogh, V, Tornaritis, M, Börnhorst, C, Hebestreit, A, Pigeot, I, and Lissner, L
Published: 2014
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35. Alcohol consumption patterns, diet and body weight in 10 European countries

Author: Sieri, S., Krogh, V., Saieva, C., Grobbee, D.E., Bergmann, M., Rohrmann, S., Tjonneland, A., Ferrari, P., Chloptsios, Y., Dilis, V., Jenab, M., Linseisen, J., Wallstrom, P., Johansson, I., Chirlaque, M.D., Sanchez, M.J., Niravong, M., Clavel-Chapelon, F., Welch, A.A., Allen, N.E., Bueno-de-Mesquita, H.B., van der Schouw, Y.T., Sacerdote, C., Panico, S., Parr, C.L., Braaten, T., Olsen, A., Jensen, M.K., Bingham, S., Riboli, E., and Slimani, N.
Subjects: Drinking of alcoholic beverages -- Health aspects -- Demographic aspects -- Analysis, Body weight -- Analysis -- Health aspects, Diet -- Health aspects -- Analysis, Food/cooking/nutrition, Health
Abstract: Background/objectives: Europe has the highest level of alcohol consumption in the world. As drinking patterns are important determinants of the beneficial and harmful effects of alcohol consumption, we investigated alcohol consumption in relation to nutrient intake, place of consumption, education and body weight in a sample of adults from 10 European countries. Methods: A 24-h dietary recall interview was conducted on 13 025 men and 23 009 women, aged 35-74 years, from 27 centres participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Means and standard errors of alcohol consumption, adjusted for age, were calculated, stratified by gender and centre. Results: In many centres, higher level drinkers (males consuming >24 g of ethanol/day, equivalent to 42 standard drinks and females consuming >12 g of ethanol/day equivalent to >1 standard drink) obtained more energy from fat and protein and less from sugar than did abstainers. The proportion of energy from starch tended to be higher for male and lower for female higher level drinkers than for abstainers. Female higher level drinkers had a lower body mass index than did abstainers, whereas male higher level drinkers generally weighed more. Male higher level drinkers were less educated than abstainers in Mediterranean countries, but were more educated elsewhere. Female higher level drinkers were usually more educated than were abstainers. Outside the home, consumption (both genders) tended to be at friends' homes, particularly among men in Northern and Central Europe, and in bars in Spain. Conclusions: This study reveals clear geographical differences in drinking habits across Europe, and shows that the characteristics of different alcohol consumption categories also vary. doi: 10.1038/ejcn.2009.76 Keywords: Alcohol; EPIC; 24-h dietary recall; EPIC-Soft; ENDB, Introduction Europe has the highest level of alcohol consumption in the world (Rehm et al., 2003a). Studies on drinking patterns across Europe, in terms of place of consumption, types of [...]
Published: 2009
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36. Food intake and risk of cutaneous melanoma in an Italian population

Author: Vinceti, M, Bonvicini, F, Pellacani, G, Sieri, S, Malagoli, C, Giusti, F, Krogh, V, Bergomi, M, and Seidenari, S
Published: 2008
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37. A multi-omics approach to investigate the inflammatory response to life course socioeconomic position

Author: Castagné, R., Kelly-Irving, M., Krogh, V., Palli, D., Panico, S., Sacerdote, C., Tumino, R., Hebels, D.G.A.J., Kleinjans, J.C.S., De Kok, T.M.C.M., Georgiadis, P., Kyrtopoulos, S.A., Vermeulen, R., Stringhini, S., Vineis, P., Chadeau-Hyam, M., Delpierre, C., IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, RS: MERLN - Instructive Biomaterials Engineering (IBE), CBITE, RS: MERLN - Cell Biology - Inspired Tissue Engineering (CBITE), Toxicogenomics, RS: GROW - R1 - Prevention, RS: FSE MaCSBio, RS: FPN MaCSBio, RS: FHML MaCSBio, Division Instructive Biomaterials Eng, Cancer Research UK, Commission of the European Communities, IRAS OH Epidemiology Chemical Agents, and dIRAS RA-2
Subjects: 0301 basic medicine, Male, Cancer Research, STRESS, Social Determinants of Health, Life course epidemiology, CHILDHOOD, Bioinformatics, Epigenome, 0302 clinical medicine, Gene expression, 030212 general & internal medicine, GENE-EXPRESSION, Genetics & Heredity, DNA methylation, socioeconomic position, Methylation, Middle Aged, Socioeconomic position, CpG site, Italy, life course epidemiology, symbols, Life course approach, Female, HEALTH, medicine.symptom, Life Sciences & Biomedicine, Adult, Inflammation, Biology, 03 medical and health sciences, symbols.namesake, Genetics, medicine, Humans, ddc:613, 0604 Genetics, Science & Technology, CHRONIC LYMPHOCYTIC-LEUKEMIA, Protein, Cancer, 1103 Clinical Sciences, medicine.disease, SOCIAL DETERMINANTS, 030104 developmental biology, Bonferroni correction, Social Class, inflammation, CELLS, gene expression, RISK-FACTORS, BLOOD-SAMPLES, CpG Islands, protein
Abstract: Aim: Inflammation represents a potential pathway through which socioeconomic position (SEP) is biologically embedded. Materials & methods: We analyzed inflammatory biomarkers in response to life course SEP by integrating multi-omics DNA-methylation, gene expression and protein level in 178 European Prospective Investigation into Cancer and Nutrition-Italy participants. Results & conclusion: We identified 61 potential cis acting CpG loci whose methylation levels were associated with gene expression at a Bonferroni correction. We examined the relationships between life course SEP and these 61 cis-acting regulatory methylation sites individually and jointly using several scores. Less-advantaged SEP participants exhibit, later in life, a lower inflammatory methylome score, suggesting an overall increased expression of the corresponding inflammatory genes or proteins, supporting the hypothesis that SEP impacts adult physiology through inflammation.
Published: 2020

38. Polyphenol intake and differentiated thyroid cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Author: Zamora-Ros, R., Cayssials, V., Franceschi, S., Kyrø, C., Weiderpass, E., Hennings, J., Sandström, M., Tjønneland, A., Olsen, A., Overvad, K., Boutron-Ruault, M.-C., Truong, T., Mancini, F.R., Katzke, V., Kühn, T., Boeing, H., Trichopoulou, A., Karakatsani, A., Martimianaki, G., Palli, D., Krogh, V., Panico, S., Tumino, R., Sacerdote, C., Lasheras, C., Rodríguez-Barranco, M., Amiano, P., Colorado-Yohar, S.M., Ardanaz, E., Almquist, M., Ericson, U., Bueno-de-Mesquita, H.B., Vermeulen, R., Byrnes, G., Scalbert, A., Agudo, A., Rinaldi, S., IRAS OH Epidemiology Chemical Agents, and dIRAS RA-2
Subjects: flavonoids, thyroid cancer, cohort, EPIC, intake, polyphenols
Abstract: Polyphenols are bioactive compounds with several anticarcinogenic activities; however, human data regarding associations with thyroid cancer (TC) is still negligible. Our aim was to evaluate the association between intakes of total, classes and subclasses of polyphenols and risk of differentiated TC and its main subtypes, papillary and follicular, in a European population. The European Prospective Investigation into Cancer and Nutrition cohort included 476,108 men and women from 10 European countries. During a mean follow-up of 14 years, there were 748 incident differentiated TC cases, including 601 papillary and 109 follicular tumors. Polyphenol intake was estimated at baseline using validated center/country-specific dietary questionnaires and the Phenol-Explorer database. In multivariable-adjusted Cox regression models, no association between total polyphenol and the risks of overall differentiated TC (HRQ4 vs. Q1 = 0.99, 95% confidence interval [CI] 0.77–1.29), papillary (HRQ4 vs. Q1 = 1.06, 95% CI 0.80–1.41) or follicular TC (HRQ4 vs. Q1 = 1.10, 95% CI 0.55–2.22) were found. No associations were observed either for flavonoids, phenolic acids or the rest of classes and subclasses of polyphenols. After stratification by body mass index (BMI), an inverse association between the intake of polyphenols (p-trend = 0.019) and phenolic acids (p-trend = 0.007) and differentiated TC risk in subjects with BMI ≥ 25 was observed. In conclusion, our study showed no associations between dietary polyphenol intake and differentiated TC risk; although further studies are warranted to investigate the potential protective associations in overweight and obese individuals.
Published: 2020

39. Mediating effect of soluble B-cell activation immune markers on the association between anthropometric and lifestyle factors and lymphoma development

Author: Saberi Hosnijeh, F. Kolijn, P.M. Casabonne, D. Nieters, A. Solans, M. Naudin, S. Ferrari, P. Mckay, J.D. Weiderpass, E. Perduca, V. Besson, C. Mancini, F.R. Masala, G. Krogh, V. Ricceri, F. Huerta, J.M. Petrova, D. Sala, N. Trichopoulou, A. Karakatsani, A. La Vecchia, C. Kaaks, R. Canzian, F. Aune, D. Boeing, H. Schulze, M.B. Perez-Cornago, A. Langerak, A.W. van der Velden, V.H.J. Vermeulen, R.
Subjects: immune system diseases, hemic and lymphatic diseases
Abstract: Sustained B-cell activation is an important mechanism contributing to B-cell lymphoma (BCL). We aimed to validate four previously reported B-cell activation markers predictive of BCL risk (sCD23, sCD27, sCD30, and CXCL13) and to examine their possible mediating effects on the association between anthropometric and lifestyle factors and major BCL subtypes. Pre-diagnostic serum levels were measured for 517 BCL cases and 525 controls in a nested case–control study. The odds ratios of BCL were 6.2 in the highest versus lowest quartile for sCD23, 2.6 for sCD30, 4.2 for sCD27, and 2.6 for CXCL13. Higher levels of all markers were associated with increased risk of chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL). Following mutual adjustment for the other immune markers, sCD23 remained associated with all subtypes and CXCL13 with FL and DLBCL. The associations of sCD23 with CLL and DLBCL and CXCL13 with DLBCL persisted among cases sampled > 9 years before diagnosis. sCD23 showed a good predictive ability (area under the curve = 0.80) for CLL, in particular among older, male participants. sCD23 and CXCL13 showed a mediating effect between body mass index (positive) and DLBCL risk, while CXCL13 contributed to the association between physical activity (inverse) and DLBCL. Our data suggest a role of B-cell activation in BCL development and a mediating role of the immune system for lifestyle factors. © 2020, The Author(s).
Published: 2020

40. Predicted basal metabolic rate and cancer risk in the European Prospective Investigation into Cancer and Nutrition

Author: Kliemann, N. Murphy, N. Viallon, V. Freisling, H. Tsilidis, K.K. Rinaldi, S. Mancini, F.R. Fagherazzi, G. Boutron-Ruault, M.-C. Boeing, H. Schulze, M.B. Masala, G. Krogh, V. Sacerdote, C. de Magistris, M.S. Bueno-de-Mesquita, B. Weiderpass, E. Kühn, T. Kaaks, R. Jakszyn, P. Redondo-Sánchez, D. Amiano, P. Chirlaque, M.-D. Gurrea, A.B. Ericson, U. Drake, I. Nøst, T.H. Aune, D. May, A.M. Tjønneland, A. Dahm, C.C. Overvad, K. Tumino, R. Quirós, J.R. Trichopoulou, A. Karakatsani, A. La Vecchia, C. Nilsson, L.M. Riboli, E. Huybrechts, I. Gunter, M.J.
Abstract: Emerging evidence suggests that a metabolic profile associated with obesity may be a more relevant risk factor for some cancers than adiposity per se. Basal metabolic rate (BMR) is an indicator of overall body metabolism and may be a proxy for the impact of a specific metabolic profile on cancer risk. Therefore, we investigated the association of predicted BMR with incidence of 13 obesity-related cancers in the European Prospective Investigation into Cancer and Nutrition (EPIC). BMR at baseline was calculated using the WHO/FAO/UNU equations and the relationships between BMR and cancer risk were investigated using multivariable Cox proportional hazards regression models. A total of 141,295 men and 317,613 women, with a mean follow-up of 14 years were included in the analysis. Overall, higher BMR was associated with a greater risk for most cancers that have been linked with obesity. However, among normal weight participants, higher BMR was associated with elevated risks of esophageal adenocarcinoma (hazard ratio per 1-standard deviation change in BMR [HR1-SD]: 2.46; 95% CI 1.20; 5.03) and distal colon cancer (HR1-SD: 1.33; 95% CI 1.001; 1.77) among men and with proximal colon (HR1-SD: 1.16; 95% CI 1.01; 1.35), pancreatic (HR1-SD: 1.37; 95% CI 1.13; 1.66), thyroid (HR1-SD: 1.65; 95% CI 1.33; 2.05), postmenopausal breast (HR1-SD: 1.17; 95% CI 1.11; 1.22) and endometrial (HR1-SD: 1.20; 95% CI 1.03; 1.40) cancers in women. These results indicate that higher BMR may be an indicator of a metabolic phenotype associated with risk of certain cancer types, and may be a useful predictor of cancer risk independent of body fatness. © 2019 International Agency for Research on Cancer (IARC/WHO); licensed by UICC
Published: 2020

41. A nutrient-wide association study for risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition and the Netherlands Cohort Study

Author: Papadimitriou, N. Muller, D. van den Brandt, P.A. Geybels, M. Patel, C.J. Gunter, M.J. Lopez, D.S. Key, T.J. Perez-Cornago, A. Ferrari, P. Vineis, P. Weiderpass, E. Boeing, H. Agudo, A. Sánchez, M.-J. Overvad, K. Kühn, T. Fortner, R.T. Palli, D. Drake, I. Bjartell, A. Santiuste, C. Bueno-de-Mesquita, B.H. Krogh, V. Tjønneland, A. Lauritzen, D.F. Gurrea, A.B. Quirós, J.R. Stattin, P. Trichopoulou, A. Martimianaki, G. Karakatsani, A. Thysell, E. Johansson, I. Ricceri, F. Tumino, R. Larrañaga, N. Khaw, K.T. Riboli, E. Tzoulaki, I. Tsilidis, K.K.
Abstract: Purpose: The evidence from the literature regarding the association of dietary factors and risk of prostate cancer is inconclusive. Methods: A nutrient-wide association study was conducted to systematically and comprehensively evaluate the associations between 92 foods or nutrients and risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC). Cox proportional hazard regression models adjusted for total energy intake, smoking status, body mass index, physical activity, diabetes and education were used to estimate hazard ratios and 95% confidence intervals for standardized dietary intakes. As in genome-wide association studies, correction for multiple comparisons was applied using the false discovery rate (FDR ' 5%) method and suggested results were replicated in an independent cohort, the Netherlands Cohort Study (NLCS). Results: A total of 5916 and 3842 incident cases of prostate cancer were diagnosed during a mean follow-up of 14 and 20 years in EPIC and NLCS, respectively. None of the dietary factors was associated with the risk of total prostate cancer in EPIC (minimum FDR-corrected P, 0.37). Null associations were also observed by disease stage, grade and fatality, except for positive associations observed for intake of dry cakes/biscuits with low-grade and butter with aggressive prostate cancer, respectively, out of which the intake of dry cakes/biscuits was replicated in the NLCS. Conclusions: Our findings provide little support for an association for the majority of the 92 examined dietary factors and risk of prostate cancer. The association of dry cakes/biscuits with low-grade prostate cancer warrants further replication given the scarcity in the literature. © 2019, The Author(s).
Published: 2020

42. Menstrual factors, reproductive history, hormone use, and urothelial carcinoma risk: a prospective study in the EPIC cohort

Author: Lujan-Barroso, L. Botteri, E. Caini, S. Ljungberg, B.F. Roswall, N. Tjønneland, A. Bueno-De-Mesquita, B. Gram, I.T. Tumino, R. Kiemeney, L.A. Liedberg, F. Stocks, T. Gunter, M.J. Murphy, N. Cervenka, I. Fournier, A. Kvaskoff, M. Haggstrom, C. Overvad, K. Lund, E. Waaseth, M. Fortner, R.T. Kuhn, T. Menendez, V. Sanchez, M.-J. Santiuste, C. Perez-Cornago, A. Zamora-Ros, R. Cross, A.J. Trichopoulou, A. Karakatsani, A. Peppa, E. Palli, D. Krogh, V. Sciannameo, V. Mattiello, A. Panico, S. van Gils, C.H. Charlotte Onland-Moret, N. Barricarte, A. Amiano, P. Khaw, K.-T. Boeing, H. Weiderpass, E. Duell, E.J.
Abstract: Background: Urothelial carcinoma is the predominant (95%) bladder cancer subtype in industrialized nations. Animal and epidemiologic human studies suggest that hormonal factors may influence urothelial carcinoma risk. Methods: We used an analytic cohort of 333,919 women from the European Prospective Investigation into Cancer and Nutrition Cohort. Associations between hormonal factors and incident urothelial carcinoma (overall and by tumor grade, tumor aggressiveness, and non–muscle-invasive urothelial carcinoma) risk were evaluated using Cox proportional hazards models. Results: During a mean of 15 years of follow-up, 529 women developed urothelial carcinoma. In a model including number of full-term pregnancies (FTP), menopausal status, and menopausal hormone therapy (MHT), number of FTP was inversely associated with urothelial carcinoma risk (HR≥5vs1 ¼ 0.48; 0.25–0.90; Ptrend in parous women ¼ 0.010) and MHT use (compared with nonuse) was positively associated with urothelial carcinoma risk (HR ¼ 1.27; 1.03–1.57), but no dose response by years of MHT use was observed. No modification of HRs by smoking status was observed. Finally, sensitivity analyses in never smokers showed similar HR patterns for the number of FTP, while no association between MHT use and urothelial carcinoma risk was observed. Association between MHT use and urothelial carcinoma risk remained significant only in current smokers. No heterogeneity of the risk estimations in the final model was observed by tumor aggressiveness or by tumor grade. A positive association between MTH use and non–muscle-invasive urothelial carcinoma risk was observed. Conclusions: Our results support that increasing the number of FTP may reduce urothelial carcinoma risk. Impact: More detailed studies on parity are needed to understand the possible effects of perinatal hormone changes in urothelial cells. © 2020 American Association for Cancer Research.
Published: 2020

43. Polyphenol intake and differentiated thyroid cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Author: Zamora-Ros, R. Cayssials, V. Franceschi, S. Kyrø, C. Weiderpass, E. Hennings, J. Sandström, M. Tjønneland, A. Olsen, A. Overvad, K. Boutron-Ruault, M.-C. Truong, T. Mancini, F.R. Katzke, V. Kühn, T. Boeing, H. Trichopoulou, A. Karakatsani, A. Martimianaki, G. Palli, D. Krogh, V. Panico, S. Tumino, R. Sacerdote, C. Lasheras, C. Rodríguez-Barranco, M. Amiano, P. Colorado-Yohar, S.M. Ardanaz, E. Almquist, M. Ericson, U. Bueno-de-Mesquita, H.B. Vermeulen, R. Schmidt, J.A. Byrnes, G. Scalbert, A. Agudo, A. Rinaldi, S.
Subjects: food and beverages
Abstract: Polyphenols are bioactive compounds with several anticarcinogenic activities; however, human data regarding associations with thyroid cancer (TC) is still negligible. Our aim was to evaluate the association between intakes of total, classes and subclasses of polyphenols and risk of differentiated TC and its main subtypes, papillary and follicular, in a European population. The European Prospective Investigation into Cancer and Nutrition cohort included 476,108 men and women from 10 European countries. During a mean follow-up of 14 years, there were 748 incident differentiated TC cases, including 601 papillary and 109 follicular tumors. Polyphenol intake was estimated at baseline using validated center/country-specific dietary questionnaires and the Phenol-Explorer database. In multivariable-adjusted Cox regression models, no association between total polyphenol and the risks of overall differentiated TC (HRQ4 vs. Q1 = 0.99, 95% confidence interval [CI] 0.77–1.29), papillary (HRQ4 vs. Q1 = 1.06, 95% CI 0.80–1.41) or follicular TC (HRQ4 vs. Q1 = 1.10, 95% CI 0.55–2.22) were found. No associations were observed either for flavonoids, phenolic acids or the rest of classes and subclasses of polyphenols. After stratification by body mass index (BMI), an inverse association between the intake of polyphenols (p-trend = 0.019) and phenolic acids (p-trend = 0.007) and differentiated TC risk in subjects with BMI ≥ 25 was observed. In conclusion, our study showed no associations between dietary polyphenol intake and differentiated TC risk; although further studies are warranted to investigate the potential protective associations in overweight and obese individuals. © 2019 UICC
Published: 2020

44. Dietary and circulating fatty acids and ovarian cancer risk in the European Prospective Investigation into Cancer and Nutrition

Author: Yammine, S. Huybrechts, I. Biessy, C. Dossus, L. Aglago, E.K. Naudin, S. Ferrari, P. Weiderpass, E. Tjønneland, A. Hansen, L. Overvad, K. Mancini, F.R. Boutron-Ruault, M.-C. Kvaskoff, M. Fortner, R.T. Kaaks, R. Schulze, M.B. Boeing, H. Trichopoulou, A. Karakatsani, A. Vecchia, C.L. Benetou, V. Masala, G. Krogh, V. Mattiello, A. Macciotta, A. Gram, I.T. Skeie, G. Quiros, J.R. Agudo, A. Sanchez, M.-J. Chirlaque, M.-D. Ardanaz, E. Gil, L. Sartor, H. Drake, I. Idahl, A. Lundin, E. Aune, D. Ward, H. Merritt, M.A. Allen, N.E. Gunter, M.J. Chajes, V.
Abstract: Background: Fatty acids impact obesity, estrogens, and inflammation, which are risk factors for ovarian cancer. Few epidemiologic studies have investigated the association of fatty acids with ovarian cancer. Methods: Within the European Prospective Investigation into Cancer and Nutrition (EPIC), 1,486 incident ovarian cancer cases were identified. Cox proportional hazard models with adjustment for ovarian cancer risk factors were used to estimate HRs of ovarian cancer across quintiles of intake of fatty acids. False discovery rate was computed to control for multiple testing. Multivariable conditional logistic regression models were used to estimate ORs of ovarian cancer across tertiles of plasma fatty acids among 633 cases and two matched controls in a nested case–control analysis. Results: A positive association was found between ovarian cancer and intake of industrial trans elaidic acid [HR comparing fifth with first quintileQ5-Q1 ¼ 1.29; 95% confidence interval (CI) ¼ 1.03–1.62; Ptrend ¼ 0.02, q-value ¼ 0.06]. Dietary intakes of n-6 linoleic acid (HRQ5-Q1 ¼ 1.10; 95% CI ¼ 1.01–1.21; Ptrend ¼ 0.03) and n-3 a-linolenic acid (HRQ5-Q1 ¼ 1.18; 95% CI ¼ 1.05–1.34; Ptrend ¼ 0.007) from deep-frying fats were also positively associated with ovarian cancer. Suggestive associations were reported for circulating elaidic (OR comparing third with first tertileT3-T1 ¼ 1.39; 95% CI ¼ 0.99–1.94; Ptrend ¼ 0.06) and a-linolenic acids (ORT3-T1 ¼ 1.30; 95% CI ¼ 0.98–1.72; Ptrend ¼ 0.06). Conclusions: Our results suggest that higher intakes and circulating levels of industrial trans elaidic acid, and higher intakes of linoleic acid and a-linolenic acid from deep-frying fat, may be associated with greater risk of ovarian cancer. Impact: If causal, eliminating industrial trans-fatty acids could offer a straightforward public health action for reducing ovarian cancer risk. © 2020 American Association for Cancer Research.
Published: 2020

45. Dietary intake of advanced glycation end products (AGEs) and changes in body weight in European adults

Author: Cordova, R. Knaze, V. Viallon, V. Rust, P. Schalkwijk, C.G. Weiderpass, E. Wagner, K.-H. Mayen-Chacon, A.-L. Aglago, E.K. Dahm, C.C. Overvad, K. Tjønneland, A. Halkjær, J. Mancini, F.R. Boutron-Ruault, M.-C. Fagherazzi, G. Katzke, V. Kühn, T. Schulze, M.B. Boeing, H. Trichopoulou, A. Karakatsani, A. Thriskos, P. Masala, G. Krogh, V. Panico, S. Tumino, R. Ricceri, F. Spijkerman, A. Boer, J. Skeie, G. Rylander, C. Borch, K.B. Quirós, J.R. Agudo, A. Redondo-Sánchez, D. Amiano, P. Gómez-Gómez, J.-H. Barricarte, A. Ramne, S. Sonestedt, E. Johansson, I. Esberg, A. Tong, T. Aune, D. Tsilidis, K.K. Gunter, M.J. Jenab, M. Freisling, H.
Abstract: Purpose: Advanced glycation end products (AGEs) can be formed in foods by the reaction of reducing sugars with proteins, and have been shown to induce insulin resistance and obesity in experimental studies. We examined the association between dietary AGEs intake and changes in body weight in adults over an average of 5 years of follow-up. Methods: A total of 255,170 participants aged 25–70 years were recruited in ten European countries (1992–2000) in the PANACEA study (Physical Activity, Nutrition, Alcohol, Cessation of smoking, Eating out of home in relation to Anthropometry), a sub-cohort of the EPIC (European Prospective Investigation into Cancer and Nutrition). Body weight was measured at recruitment and self-reported between 2 and 11 years later depending on the study center. A reference database for AGEs was used containing UPLC–MS/MS-measured Nε-(carboxymethyl)-lysine (CML), Nε-(1-carboxyethyl)-lysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) in 200 common European foods. This reference database was matched to foods and decomposed recipes obtained from country-specific validated dietary questionnaires in EPIC and intake levels of CEL, CML, and MG-H1 were estimated. Associations between dietary AGEs intake and body weight change were estimated separately for each of the three AGEs using multilevel mixed linear regression models with center as random effect and dietary AGEs intake and relevant confounders as fixed effects. Results: A one-SD increment in CEL intake was associated with 0.111 kg (95% CI 0.087–0.135) additional weight gain over 5 years. The corresponding additional weight gain for CML and MG-H1 was 0.065 kg (0.041–0.089) and 0.034 kg (0.012, 0.057), respectively. The top six food groups contributing to AGEs intake, with varying proportions across the AGEs, were cereals/cereal products, meat/processed meat, cakes/biscuits, dairy, sugar and confectionary, and fish/shellfish. Conclusion: In this study of European adults, higher intakes of AGEs were associated with marginally greater weight gain over an average of 5 years of follow-up. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature.
Published: 2020

46. Glycemic index, glycemic load, and risk of coronary heart disease: A pan-European cohort study

Author: Sieri, S. Agnoli, C. Grioni, S. Weiderpass, E. Mattiello, A. Sluijs, I. Sanchez, M.J. Jakobsen, M.U. Sweeting, M. van der Schouw, Y.T. Nilsson, L.M. Wennberg, P. Katzke, V.A. Kühn, T. Overvad, K. Tong, T.Y.N. Conchi, M.-I. Quirós, J.R. García-Torrecillas, J.M. Mokoroa, O. Gómez, J.-H. Tjønneland, A. Sonestedt, E. Trichopoulou, A. Karakatsani, A. Valanou, E. Boer, J.M.A. Monique Verschuren, W.M. Boutron-Ruault, M.-C. Fagherazzi, G. Madika, A.-L. Bergmann, M.M. Schulze, M.B. Ferrari, P. Freisling, H. Lennon, H. Sacerdote, C. Masala, G. Tumino, R. Riboli, E. Wareham, N.J. Danesh, J. Forouhi, N.G. Butterworth, A.S. Krogh, V.
Abstract: Background: High carbohydrate intake raises blood triglycerides, glucose, and insulin; reduces HDLs; and may increase risk of coronary heart disease (CHD). Epidemiological studies indicate that high dietary glycemic index (GI) and glycemic load (GL) are associated with increased CHD risk. Objectives: The aim of this study was to determine whether dietary GI, GL, and available carbohydrates are associated with CHD risk in both sexes. Methods: This large prospective study-the European Prospective Investigation into Cancer and Nutrition-consisted of 338,325 participants who completed a dietary questionnaire. HRs with 95% CIs for a CHD event, in relation to intake of GI, GL, and carbohydrates, were estimated using covariate-adjusted Cox proportional hazard models. Results: After 12.8 y (median), 6378 participants had experienced a CHD event. High GL was associated with greater CHD risk [HR 1.16 (95% CI: 1.02, 1.31) highest vs. lowest quintile, p-trend 0.035; HR 1.18 (95% CI: 1.07, 1.29) per 50 g/day of GL intake]. The association between GL and CHD risk was evident in subjects with BMI (in kg/m2) =25 [HR: 1.22 (95% CI: 1.11, 1.35) per 50 g/d] but not in those with BMI
Published: 2020

47. Mediating effect of soluble B-cell activation immune markers on the association between anthropometric and lifestyle factors and lymphoma development

Author: Saberi Hosnijeh, F. (Fatemeh), Kolijn, P.M. (Pieter M.), Casabonne, D. (Delphine), Nieters, A. (Alexandra), Solans, M. (Marta), Naudin, S. (Sabine), Ferrari, P. (Pietro), Mckay, J.D. (James D.), Weiderpass, E. (Elisabete), Perduca, V. (Vittorio), Besson, C. (Caroline), Mancini, F.R. (Francesca Romana), Masala, G. (Giovanna), Krogh, V. (Vittorio), Ricceri, F. (Fulvio), Huerta, J.M. (José M.), Petrova, D. (Dafina), Sala, N. (Núria), Trichopoulou, A. (Antonia), Karakatsani, A. (Anna), La Vecchia, C. (Carlo), Kaaks, R. (Rudolf), Canzian, F. (Federico), Aune, D. (Dagfinn), Boeing, H. (Heiner), Schulze, M.B. (Matthias), Perez-Cornago, A. (Aurora), Langerak, A.W. (Anton), Velden, V.H.J. (Vincent) van der, Vermeulen, R. (Roel), Saberi Hosnijeh, F. (Fatemeh), Kolijn, P.M. (Pieter M.), Casabonne, D. (Delphine), Nieters, A. (Alexandra), Solans, M. (Marta), Naudin, S. (Sabine), Ferrari, P. (Pietro), Mckay, J.D. (James D.), Weiderpass, E. (Elisabete), Perduca, V. (Vittorio), Besson, C. (Caroline), Mancini, F.R. (Francesca Romana), Masala, G. (Giovanna), Krogh, V. (Vittorio), Ricceri, F. (Fulvio), Huerta, J.M. (José M.), Petrova, D. (Dafina), Sala, N. (Núria), Trichopoulou, A. (Antonia), Karakatsani, A. (Anna), La Vecchia, C. (Carlo), Kaaks, R. (Rudolf), Canzian, F. (Federico), Aune, D. (Dagfinn), Boeing, H. (Heiner), Schulze, M.B. (Matthias), Perez-Cornago, A. (Aurora), Langerak, A.W. (Anton), Velden, V.H.J. (Vincent) van der, and Vermeulen, R. (Roel)
Abstract: Sustained B-cell activation is an important mechanism contributing to B-cell lymphoma (BCL). We aimed to validate four previously reported B-cell activation markers predictive of BCL risk (sCD23, sCD27, sCD30, and CXCL13) and to examine their possible mediating effects on the association between anthropometric and lifestyle factors and major BCL subtypes. Pre-diagnostic serum levels were measured for 517 BCL cases and 525 controls in a nested case–control study. The odds ratios of BCL were 6.2 in the highest versus lowest quartile for sCD23, 2.6 for sCD30, 4.2 for sCD27, and 2.6 for CXCL13. Higher levels of all markers were associated with increased risk of chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), and diffuse large B-cell lymphoma (DLBCL). Following mutual adjustment for the other immune markers, sCD23 remained associated with all subtypes and CXCL13 with FL and DLBCL. The associations of sCD23 with CLL and DLBCL and CXCL13 with DLBCL persisted among cases sampled > 9 years before diagnosis. sCD23 showed a good predictive ability (area under the curve = 0.80) for CLL, in particular among older, male participants. sCD23 and CXCL13 showed a mediating effect between body mass index (positive) and DLBCL risk, while CXCL13 contributed to the association between physical activity (inverse) and DLBCL. Our data suggest a role of B-cell activation in BCL development and a mediating role of the immune system for lifestyle factors.
Published: 2020
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48. Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length

Author: Li, C. (Chen), Stoma, S. (Svetlana), Lotta, L.A. (Luca A.), Warner, S. (Sophie), Albrecht, E. (Eva), Allione, A. (Alessandra), Arp, P.P. (Pascal), Broer, L. (Linda), Buxton, J.L. (Jessica L.), Da Silva Couto Alves, A. (Alexessander), Deelen, J. (Joris), Fedko, I.O. (Iryna O.), Gordon, S.D. (Scott D.), Jiang, T. (Tao), Karlsson, R. (Robert), Kerrison, N. (Nicola), Loe, T.K. (Taylor K.), Mangino, M. (Massimo), Milaneschi, Y. (Yuri), Miraglio, B. (Benjamin), Pervjakova, N. (Natalia), Russo, A. (Alessia), Surakka, I. (Ida), Spek, A. (Ashley) van der, Verhoeven, J.E. (Josine E.), Amin, N. (Najaf), Beekman, M. (Marian), Blakemore, A.I. (Alexandra I.), Canzian, F. (Federico), Hamby, S.E. (Stephen E.), Hottenga, J.J. (Jouke Jan), Jones, P.D. (Peter D.), Jousilahti, P. (Pekka), Mägi, R. (Reedik), Medland, S.E. (Sarah), Montgomery, G.W. (Grant), Nyholt, D.R. (Dale), Perola, M. (Markus), Pietilainen, K.H. (Kirsi Hannele), Salomaa, V. (Veikko), Sillanpää, E. (Elina), Suchiman, H.E. (H. Eka), Heemst, D. (Diana) van, Willemsen, G. (Gonneke), Agudo, A. (Antonio), Boeing, H. (Heiner), Boomsma, D.I. (Dorret), Chirlaque, M.D. (M.), Fagherazzi, G. (Guy), Ferrari, P. (Pietro), Franks, P. (Paul), Gieger, C. (Christian), Hagen, K. (Knut), Gunter, M.J. (Marc J.), Hägg, S. (Sara), Hovatta, I. (Iiris), Imaz, L. (Liher), Kaprio, J. (Jaakko), Kaaks, R. (Rudolf), Key, T. (Tim), Krogh, V. (Vittorio), Martin, N.G. (Nicholas), Melander, O. (Olle), Metspalu, A. (Andres), Moreno, C. (Concha), Onland-Moret, N.C. (N. Charlotte), Nilsson, P. (Peter), Ong, K.K. (Ken K.), Overvad, K. (Kim), Palli, D. (Domenico), Panico, S. (Salvatore), Pedersen, N.L. (Nancy), Penninx, B.W.J.H. (Brenda), Quirós, J.R., Jarvelin, M.R. (Marjo Riitta), Rodríguez-Barranco, M. (Miguel), Scott, R.A. (Robert A.), Severi, G. (Gianluca), Slagboom, P.E. (Eline), Spector, T.D. (Timothy), Tjønneland, A. (Anne), Trichopoulou, A. (Antonia), Tumino, R. (Rosario), Uitterlinden, A.G. (André G.), Schouw, Y.T. (Yvonne) van der, Duijn, C.M. (Cornelia) van, Weiderpass, E. (Elisabete), Denchi, E.L. (Eros Lazzerini), Matullo, G., Butterworth, A.S. (Adam S.), Danesh, J. (John), Samani, N.J. (Nilesh), Wareham, N.J. (Nick), Nelson, C.P. (Christopher P.), Langenberg, C. (Claudia), Codd, V. (Veryan), Li, C. (Chen), Stoma, S. (Svetlana), Lotta, L.A. (Luca A.), Warner, S. (Sophie), Albrecht, E. (Eva), Allione, A. (Alessandra), Arp, P.P. (Pascal), Broer, L. (Linda), Buxton, J.L. (Jessica L.), Da Silva Couto Alves, A. (Alexessander), Deelen, J. (Joris), Fedko, I.O. (Iryna O.), Gordon, S.D. (Scott D.), Jiang, T. (Tao), Karlsson, R. (Robert), Kerrison, N. (Nicola), Loe, T.K. (Taylor K.), Mangino, M. (Massimo), Milaneschi, Y. (Yuri), Miraglio, B. (Benjamin), Pervjakova, N. (Natalia), Russo, A. (Alessia), Surakka, I. (Ida), Spek, A. (Ashley) van der, Verhoeven, J.E. (Josine E.), Amin, N. (Najaf), Beekman, M. (Marian), Blakemore, A.I. (Alexandra I.), Canzian, F. (Federico), Hamby, S.E. (Stephen E.), Hottenga, J.J. (Jouke Jan), Jones, P.D. (Peter D.), Jousilahti, P. (Pekka), Mägi, R. (Reedik), Medland, S.E. (Sarah), Montgomery, G.W. (Grant), Nyholt, D.R. (Dale), Perola, M. (Markus), Pietilainen, K.H. (Kirsi Hannele), Salomaa, V. (Veikko), Sillanpää, E. (Elina), Suchiman, H.E. (H. Eka), Heemst, D. (Diana) van, Willemsen, G. (Gonneke), Agudo, A. (Antonio), Boeing, H. (Heiner), Boomsma, D.I. (Dorret), Chirlaque, M.D. (M.), Fagherazzi, G. (Guy), Ferrari, P. (Pietro), Franks, P. (Paul), Gieger, C. (Christian), Hagen, K. (Knut), Gunter, M.J. (Marc J.), Hägg, S. (Sara), Hovatta, I. (Iiris), Imaz, L. (Liher), Kaprio, J. (Jaakko), Kaaks, R. (Rudolf), Key, T. (Tim), Krogh, V. (Vittorio), Martin, N.G. (Nicholas), Melander, O. (Olle), Metspalu, A. (Andres), Moreno, C. (Concha), Onland-Moret, N.C. (N. Charlotte), Nilsson, P. (Peter), Ong, K.K. (Ken K.), Overvad, K. (Kim), Palli, D. (Domenico), Panico, S. (Salvatore), Pedersen, N.L. (Nancy), Penninx, B.W.J.H. (Brenda), Quirós, J.R., Jarvelin, M.R. (Marjo Riitta), Rodríguez-Barranco, M. (Miguel), Scott, R.A. (Robert A.), Severi, G. (Gianluca), Slagboom, P.E. (Eline), Spector, T.D. (Timothy), Tjønneland, A. (Anne), Trichopoulou, A. (Antonia), Tumino, R. (Rosario), Uitterlinden, A.G. (André G.), Schouw, Y.T. (Yvonne) van der, Duijn, C.M. (Cornelia) van, Weiderpass, E. (Elisabete), Denchi, E.L. (Eros Lazzerini), Matullo, G., Butterworth, A.S. (Adam S.), Danesh, J. (John), Samani, N.J. (Nilesh), Wareham, N.J. (Nick), Nelson, C.P. (Christopher P.), Langenberg, C. (Claudia), and Codd, V. (Veryan)
Abstract: Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1, PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.
Published: 2020
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49. Polyphenol intake and differentiated thyroid cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Author: IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Zamora-Ros, R., Cayssials, V., Franceschi, S., Kyrø, C., Weiderpass, E., Hennings, J., Sandström, M., Tjønneland, A., Olsen, A., Overvad, K., Boutron-Ruault, M.-C., Truong, T., Mancini, F.R., Katzke, V., Kühn, T., Boeing, H., Trichopoulou, A., Karakatsani, A., Martimianaki, G., Palli, D., Krogh, V., Panico, S., Tumino, R., Sacerdote, C., Lasheras, C., Rodríguez-Barranco, M., Amiano, P., Colorado-Yohar, S.M., Ardanaz, E., Almquist, M., Ericson, U., Bueno-de-Mesquita, H.B., Vermeulen, R., Byrnes, G., Scalbert, A., Agudo, A., Rinaldi, S., IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Zamora-Ros, R., Cayssials, V., Franceschi, S., Kyrø, C., Weiderpass, E., Hennings, J., Sandström, M., Tjønneland, A., Olsen, A., Overvad, K., Boutron-Ruault, M.-C., Truong, T., Mancini, F.R., Katzke, V., Kühn, T., Boeing, H., Trichopoulou, A., Karakatsani, A., Martimianaki, G., Palli, D., Krogh, V., Panico, S., Tumino, R., Sacerdote, C., Lasheras, C., Rodríguez-Barranco, M., Amiano, P., Colorado-Yohar, S.M., Ardanaz, E., Almquist, M., Ericson, U., Bueno-de-Mesquita, H.B., Vermeulen, R., Byrnes, G., Scalbert, A., Agudo, A., and Rinaldi, S.
Published: 2020

50. Agnostic Cys34-albumin adductomics and DNA methylation: Implication of N-acetylcysteine in lung carcinogenesis years before diagnosis

Author: IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Dagnino, S., Bodinier, B., Grigoryan, H., Rappaport, S.M., Karimi, M., Guida, F., Polidoro, S., Edmands, W.B., Naccarati, A., Fiorito, G., Sacerdote, C., Krogh, V., Vermeulen, R., Vineis, P., Chadeau-Hyam, M., IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Dagnino, S., Bodinier, B., Grigoryan, H., Rappaport, S.M., Karimi, M., Guida, F., Polidoro, S., Edmands, W.B., Naccarati, A., Fiorito, G., Sacerdote, C., Krogh, V., Vermeulen, R., Vineis, P., and Chadeau-Hyam, M.
Published: 2020

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