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259 results on '"Barricarte Gurrea, A"'

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

Author: S. G. Yammine, I. Huybrechts, C. Biessy, L. Dossus, S. Panico, M. J. Sánchez, V. Benetou, R. Turzanski-Fortner, V. Katzke, A. Idahl, G. Skeie, K. Standahl Olsen, A. Tjønneland, J. Halkjaer, S. Colorado-Yohar, A. K. Heath, E. Sonestedt, H. Sartor, M. B. Schulze, D. Palli, M. Crous-Bou, A. Dorronsoro, K. Overvad, A. Barricarte Gurrea, G. Severi, R. C.H. Vermeulen, T. M. Sandanger, R. C. Travis, T. Key, P. Amiano, B. Van Guelpen, M. Johansson, M. Sund, R. Tumino, N. Wareham, C. Sacerdote, V. Krogh, P. Brennan, E. Riboli, E. Weiderpass, M. J. Gunter, and V. Chajès
Subjects: Fatty acids, Endometrial cancer, Epidemiology, Diet, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Abstract Background Diet may impact important risk factors for endometrial cancer such as obesity and inflammation. However, evidence on the role of specific dietary factors is limited. We investigated associations between dietary fatty acids and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods This analysis includes 1,886 incident endometrial cancer cases and 297,432 non-cases. All participants were followed up for a mean of 8.8 years. Multivariable Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of endometrial cancer across quintiles of individual fatty acids estimated from various food sources quantified through food frequency questionnaires in the entire EPIC cohort. The false discovery rate (q-values) was computed to control for multiple comparisons. Results Consumption of n-6 γ-linolenic acid was inversely associated with endometrial cancer risk (HR comparing 5th with 1st quintileQ5−Q1=0.77, 95% CI = 0.64; 0.92, ptrend=0.01, q-value = 0.15). This association was mainly driven by γ-linolenic acid derived from plant sources (HRper unit increment=0.94, 95%CI= (0.90;0.98), p = 0.01) but not from animal sources (HRper unit increment= 1.00, 95%CI = (0.92; 1.07), p = 0.92). In addition, an inverse association was found between consumption of n-3 α-linolenic acid from vegetable sources and endometrial cancer risk (HRper unit increment= 0.93, 95%CI = (0.87; 0.99), p = 0.04). No significant association was found between any other fatty acids (individual or grouped) and endometrial cancer risk. Conclusion Our results suggest that higher consumption of γ-linolenic acid and α-linoleic acid from plant sources may be associated with lower risk of endometrial cancer.
Published: 2023
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2. Pre-diagnostic C-reactive protein concentrations, CRP genetic variation and mortality among individuals with colorectal cancer in Western European populations

Author: Katharina Nimptsch, Krasimira Aleksandrova, Veronika Fedirko, Mazda Jenab, Marc J. Gunter, Peter D. Siersema, Kana Wu, Verena Katzke, Rudolf Kaaks, Salvatore Panico, Domenico Palli, Anne M May, Sabina Sieri, Bas Bueno-de-Mesquita, Karina Standahl, Maria-Jose Sánchez, Aurora Perez-Cornago, Anja Olsen, Anne Tjønneland, Catalina Bonet Bonet, Christina C. Dahm, María-Dolores Chirlaque, Valentina Fiano, Rosario Tumino, Aurelio Barricarte Gurrea, Marie-Christine Boutron-Ruault, Florence Menegaux, Gianluca Severi, Bethany van Guelpen, Young-Ae Lee, and Tobias Pischon
Subjects: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Abstract Background The role of elevated pre-diagnostic C-reactive protein (CRP) concentrations on mortality in individuals with colorectal cancer (CRC) remains unclear. Methods We investigated the association between pre-diagnostic high-sensitivity CRP concentrations and CRP genetic variation associated with circulating CRP and CRC-specific and all-cause mortality based on data from 1,235 individuals with CRC within the European Prospective Investigation into Cancer and Nutrition cohort using multivariable-adjusted Cox proportional hazards regression. Results During a median follow-up of 9.3 years, 455 CRC-specific deaths were recorded, out of 590 deaths from all causes. Pre-diagnostic CRP concentrations were not associated with CRC-specific (hazard ratio, HR highest versus lowest quintile 0.92, 95% confidence interval, CI 0.66, 1.28) or all-cause mortality (HR 0.91, 95% CI 0.68, 1.21). Genetic predisposition to higher CRP (weighted score based on alleles of four CRP SNPs associated with higher circulating CRP) was not significantly associated with CRC-specific mortality (HR per CRP-score unit 0.95, 95% CI 0.86, 1.05) or all-cause mortality (HR 0.98, 95% CI 0.90, 1.07). Among four investigated CRP genetic variants, only SNP rs1205 was significantly associated with CRC-specific (comparing the CT and CC genotypes with TT genotype, HR 0.54, 95% CI 0.35, 0.83 and HR 0.58, 95% CI 0.38, 0.88, respectively) and all-cause mortality (HR 0.58, 95% CI 0.40, 0.85 and 0.64, 95% CI 0.44, 0.92, respectively). Conclusions The results of this prospective cohort study do not support a role of pre-diagnostic CRP concentrations on mortality in individuals with CRC. The observed associations with rs1205 deserve further scientific attention.
Published: 2022
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3. Development and validation of a lifestyle-based model for colorectal cancer risk prediction: the LiFeCRC score

Author: Krasimira Aleksandrova, Robin Reichmann, Rudolf Kaaks, Mazda Jenab, H. Bas Bueno-de-Mesquita, Christina C. Dahm, Anne Kirstine Eriksen, Anne Tjønneland, Fanny Artaud, Marie-Christine Boutron-Ruault, Gianluca Severi, Anika Hüsing, Antonia Trichopoulou, Anna Karakatsani, Eleni Peppa, Salvatore Panico, Giovanna Masala, Sara Grioni, Carlotta Sacerdote, Rosario Tumino, Sjoerd G. Elias, Anne M. May, Kristin B. Borch, Torkjel M. Sandanger, Guri Skeie, Maria-Jose Sánchez, José María Huerta, Núria Sala, Aurelio Barricarte Gurrea, José Ramón Quirós, Pilar Amiano, Jonna Berntsson, Isabel Drake, Bethany van Guelpen, Sophia Harlid, Tim Key, Elisabete Weiderpass, Elom K. Aglago, Amanda J. Cross, Konstantinos K. Tsilidis, Elio Riboli, and Marc J. Gunter
Subjects: Colorectal cancer, Risk prediction, Lifestyle behaviour, Risk screening, Cancer prevention, Medicine
Abstract: Abstract Background Nutrition and lifestyle have been long established as risk factors for colorectal cancer (CRC). Modifiable lifestyle behaviours bear potential to minimize long-term CRC risk; however, translation of lifestyle information into individualized CRC risk assessment has not been implemented. Lifestyle-based risk models may aid the identification of high-risk individuals, guide referral to screening and motivate behaviour change. We therefore developed and validated a lifestyle-based CRC risk prediction algorithm in an asymptomatic European population. Methods The model was based on data from 255,482 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study aged 19 to 70 years who were free of cancer at study baseline (1992–2000) and were followed up to 31 September 2010. The model was validated in a sample comprising 74,403 participants selected among five EPIC centres. Over a median follow-up time of 15 years, there were 3645 and 981 colorectal cancer cases in the derivation and validation samples, respectively. Variable selection algorithms in Cox proportional hazard regression and random survival forest (RSF) were used to identify the best predictors among plausible predictor variables. Measures of discrimination and calibration were calculated in derivation and validation samples. To facilitate model communication, a nomogram and a web-based application were developed. Results The final selection model included age, waist circumference, height, smoking, alcohol consumption, physical activity, vegetables, dairy products, processed meat, and sugar and confectionary. The risk score demonstrated good discrimination overall and in sex-specific models. Harrell’s C-index was 0.710 in the derivation cohort and 0.714 in the validation cohort. The model was well calibrated and showed strong agreement between predicted and observed risk. Random survival forest analysis suggested high model robustness. Beyond age, lifestyle data led to improved model performance overall (continuous net reclassification improvement = 0.307 (95% CI 0.264–0.352)), and especially for young individuals below 45 years (continuous net reclassification improvement = 0.364 (95% CI 0.084–0.575)). Conclusions LiFeCRC score based on age and lifestyle data accurately identifies individuals at risk for incident colorectal cancer in European populations and could contribute to improved prevention through motivating lifestyle change at an individual level.
Published: 2021
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4. Lifestyle factors and risk of multimorbidity of cancer and cardiometabolic diseases: a multinational cohort study

Author: Heinz Freisling, Vivian Viallon, Hannah Lennon, Vincenzo Bagnardi, Cristian Ricci, Adam S. Butterworth, Michael Sweeting, David Muller, Isabelle Romieu, Pauline Bazelle, Marina Kvaskoff, Patrick Arveux, Gianluca Severi, Christina Bamia, Tilman Kühn, Rudolf Kaaks, Manuela Bergmann, Heiner Boeing, Anne Tjønneland, Anja Olsen, Kim Overvad, Christina C. Dahm, Virginia Menéndez, Antonio Agudo, Maria-Jose Sánchez, Pilar Amiano, Carmen Santiuste, Aurelio Barricarte Gurrea, Tammy Y. N. Tong, Julie A. Schmidt, Ioanna Tzoulaki, Konstantinos K. Tsilidis, Heather Ward, Domenico Palli, Claudia Agnoli, Rosario Tumino, Fulvio Ricceri, Salvatore Panico, H. Susan J. Picavet, Marije Bakker, Evelyn Monninkhof, Peter Nilsson, Jonas Manjer, Olov Rolandsson, Elin Thysell, Elisabete Weiderpass, Mazda Jenab, Elio Riboli, Paolo Vineis, John Danesh, Nick J. Wareham, Marc J. Gunter, and Pietro Ferrari
Subjects: Healthy lifestyle, Obesity, Cancer and cardiometabolic multimorbidity, Cancer, Cardiovascular disease, Diabetes, Medicine
Abstract: Abstract Background Although lifestyle factors have been studied in relation to individual non-communicable diseases (NCDs), their association with development of a subsequent NCD, defined as multimorbidity, has been scarcely investigated. The aim of this study was to investigate associations between five lifestyle factors and incident multimorbidity of cancer and cardiometabolic diseases. Methods In this prospective cohort study, 291,778 participants (64% women) from seven European countries, mostly aged 43 to 58 years and free of cancer, cardiovascular disease (CVD), and type 2 diabetes (T2D) at recruitment, were included. Incident multimorbidity of cancer and cardiometabolic diseases was defined as developing subsequently two diseases including first cancer at any site, CVD, and T2D in an individual. Multi-state modelling based on Cox regression was used to compute hazard ratios (HR) and 95% confidence intervals (95% CI) of developing cancer, CVD, or T2D, and subsequent transitions to multimorbidity, in relation to body mass index (BMI), smoking status, alcohol intake, physical activity, adherence to the Mediterranean diet, and their combination as a healthy lifestyle index (HLI) score. Cumulative incidence functions (CIFs) were estimated to compute 10-year absolute risks for transitions from healthy to cancer at any site, CVD (both fatal and non-fatal), or T2D, and to subsequent multimorbidity after each of the three NCDs. Results During a median follow-up of 11 years, 1910 men and 1334 women developed multimorbidity of cancer and cardiometabolic diseases. A higher HLI, reflecting healthy lifestyles, was strongly inversely associated with multimorbidity, with hazard ratios per 3-unit increment of 0.75 (95% CI, 0.71 to 0.81), 0.84 (0.79 to 0.90), and 0.82 (0.77 to 0.88) after cancer, CVD, and T2D, respectively. After T2D, the 10-year absolute risks of multimorbidity were 40% and 25% for men and women, respectively, with unhealthy lifestyle, and 30% and 18% for men and women with healthy lifestyles. Conclusion Pre-diagnostic healthy lifestyle behaviours were strongly inversely associated with the risk of cancer and cardiometabolic diseases, and with the prognosis of these diseases by reducing risk of multimorbidity.
Published: 2020
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5. Dietary Intake of Advanced Glycation End Products (AGEs) and Mortality among Individuals with Colorectal Cancer

Author: Ziling Mao, Elom K. Aglago, Zhiwei Zhao, Casper Schalkwijk, Li Jiao, Heinz Freisling, Elisabete Weiderpass, David J. Hughes, Anne Kirstine Eriksen, Anne Tjønneland, Gianluca Severi, Joseph Rothwell, Marie-Christine Boutron-Ruault, Verena Katzke, Rudolf Kaaks, Matthias B. Schulze, Anna Birukov, Vittorio Krogh, Salvatore Panico, Rosario Tumino, Fulvio Ricceri, H. Bas Bueno-de-Mesquita, Roel C. H. Vermeulen, Inger T. Gram, Guri Skeie, Torkjel M. Sandanger, J. Ramón Quirós, Marta Crous-Bou, Maria-Jose Sánchez, Pilar Amiano, María-Dolores Chirlaque, Aurelio Barricarte Gurrea, Jonas Manjer, Ingegerd Johansson, Aurora Perez-Cornago, Mazda Jenab, and Veronika Fedirko
Subjects: advanced glycation end-products, dietary advanced glycation end-products, all-cause mortality, colorectal cancer mortality, Nutrition. Foods and food supply, TX341-641
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
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6. A Body Shape Index (ABSI) achieves better mortality risk stratification than alternative indices of abdominal obesity: results from a large European cohort

Author: Christakoudi, Sofia, Tsilidis, Konstantinos K., Muller, David C., Freisling, Heinz, Weiderpass, Elisabete, Overvad, Kim, Söderberg, Stefan, Häggström, Christel, Pischon, Tobias, Dahm, Christina C., Zhang, Jie, Tjønneland, Anne, Halkjær, Jytte, MacDonald, Conor, Boutron-Ruault, Marie-Christine, Mancini, Francesca Romana, Kühn, Tilman, Kaaks, Rudolf, Schulze, Matthias B., Trichopoulou, Antonia, Karakatsani, Anna, Peppa, Eleni, Masala, Giovanna, Pala, Valeria, Panico, Salvatore, Tumino, Rosario, Sacerdote, Carlotta, Quirós, J. Ramón, Agudo, Antonio, Sánchez, Maria-Jose, Cirera, Lluís, Barricarte-Gurrea, Aurelio, Amiano, Pilar, Memarian, Ensieh, Sonestedt, Emily, Bueno-de-Mesquita, Bas, May, Anne M., Khaw, Kay-Tee, Wareham, Nicholas J., Tong, Tammy Y. N., Huybrechts, Inge, Noh, Hwayoung, Aglago, Elom K., Ellingjord-Dale, Merete, Ward, Heather A., Aune, Dagfinn, and Riboli, Elio
Published: 2020
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7. Evidence Update on the Relationship between Diet and the Most Common Cancers from the European Prospective Investigation into Cancer and Nutrition (EPIC) Study: A Systematic Review

Author: Esther Ubago-Guisado, Miguel Rodríguez-Barranco, Ana Ching-López, Dafina Petrova, Esther Molina-Montes, Pilar Amiano, Aurelio Barricarte-Gurrea, María-Dolores Chirlaque, Antonio Agudo, and María-José Sánchez
Subjects: colorectal cancer, breast cancer, lung cancer, prostate cancer, intake, alcohol, Nutrition. Foods and food supply, TX341-641
Abstract: The European Prospective Investigation into Cancer and Nutrition (EPIC) is a multicentre prospective study conducted in 23 centres in 10 European countries. Here we review the findings from EPIC on the relationship between diet-related exposures and incidence or mortality from the four most frequent cancers in the European population: colorectal, breast, lung, and prostate cancer. We conducted a systematic review following PRISMA guidelines and identified 110 high-quality studies based on the EPIC cohort. Fruit and vegetable consumption had a protective effect against colorectal, breast, and lung cancer, whereas only fruit had a protective effect against prostate cancer. A higher consumption of fish and lower consumption of red and processed meat were related with a lower risk of colorectal cancer; and higher consumption of fatty fish with lower risk of breast cancer. Calcium and yogurt intake were found to protect against colorectal and prostate cancer. Alcohol consumption increased the risk for colorectal and breast cancer. Finally, adherence to the Mediterranean diet emerged as a protective factor for colorectal and breast cancer. The EPIC study results are in agreement with the latest evidence from leading authorities on cancer prevention and help to inform public prevention policies and strategies.
Published: 2021
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8. Dietary Advanced Glycation End-Products and Colorectal Cancer Risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study

Author: Elom K. Aglago, Ana-Lucia Mayén, Viktoria Knaze, Heinz Freisling, Veronika Fedirko, David J. Hughes, Li Jiao, Anne Kirstine Eriksen, Anne Tjønneland, Marie-Christine Boutron-Ruault, Joseph A. Rothwell, Gianluca Severi, Rudolf Kaaks, Verena Katzke, Matthias B. Schulze, Anna Birukov, Domenico Palli, Sabina Sieri, Maria Santucci de Magistris, Rosario Tumino, Fulvio Ricceri, Bas Bueno-de-Mesquita, Jeroen W. G. Derksen, Guri Skeie, Inger Torhild Gram, Torkjel Sandanger, J. Ramón Quirós, Leila Luján-Barroso, Maria-Jose Sánchez, Pilar Amiano, María-Dolores Chirlaque, Aurelio Barricarte Gurrea, Ingegerd Johansson, Jonas Manjer, Aurora Perez-Cornago, Elisabete Weiderpass, Marc J. Gunter, Alicia K. Heath, Casper G. Schalkwijk, and Mazda Jenab
Subjects: advanced glycation end-products, dietary glycation compounds, colorectal cancer, dietary exposure, Nutrition. Foods and food supply, TX341-641
Abstract: Dietary advanced glycation end-products (dAGEs) have been hypothesized to be associated with a higher risk of colorectal cancer (CRC) by promoting inflammation, metabolic dysfunction, and oxidative stress in the colonic epithelium. However, evidence from prospective cohort studies is scarce and inconclusive. We evaluated CRC risk associated with the intake of dAGEs in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Dietary intakes of three major dAGEs: Nε-carboxy-methyllysine (CML), Nε-carboxyethyllysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) were estimated in 450,111 participants (median follow-up = 13 years, with 6162 CRC cases) by matching to a detailed published European food composition database. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of dAGEs with CRC were computed using multivariable-adjusted Cox regression models. Inverse CRC risk associations were observed for CML (HR comparing extreme quintiles: HRQ5vs.Q1 = 0.92, 95% CI = 0.85–1.00) and MG-H1 (HRQ5vs.Q1 = 0.92, 95% CI = 0.85–1.00), but not for CEL (HRQ5vs.Q1 = 0.97, 95% CI = 0.89–1.05). The associations did not differ by sex or anatomical location of the tumor. Contrary to the initial hypothesis, our findings suggest an inverse association between dAGEs and CRC risk. More research is required to verify these findings and better differentiate the role of dAGEs from that of endogenously produced AGEs and their precursor compounds in CRC development.
Published: 2021
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9. High adherence to Western dietary pattern and prostate cancer risk: findings from the EPIC‐Spain cohort

Author: Castelló, Adela, primary, Rodríguez‐Barranco, Miguel, additional, Pérez‐Gómez, Beatriz, additional, Chirlaque, Maria Dolores, additional, Bonet, Catalina, additional, Amiano, Pilar, additional, Ardanaz, Eva, additional, Huerta, José María, additional, Zamora‐Ros, Raúl, additional, Quirós, José Ramon, additional, Barricarte‐Gurrea, Aurelio, additional, Pollán, Marina, additional, and Sanchez, María‐José, additional
Published: 2023
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10. Development and validation of a lifestyle-based model for colorectal cancer risk prediction: the LiFeCRC score

Author: Amanda J. Cross, Kristin Benjaminsen Borch, Anne Kirstine Eriksen, Elio Riboli, José María Huerta, H. Bas Bueno-de-Mesquita, Giovanna Masala, Núria Sala, Anne Tjønneland, Anika Hüsing, Rudolf Kaaks, Sara Grioni, Anne M. May, Fanny Artaud, Antonia Trichopoulou, Pilar Amiano, Eleni Peppa, Marc J. Gunter, Timothy J. Key, Aurelio Barricarte Gurrea, Jonna Berntsson, Anna Karakatsani, Mazda Jenab, Elisabete Weiderpass, Isabel Drake, Christina C. Dahm, Torkjel M. Sandanger, Bethany Van Guelpen, Robin Reichmann, María José Sánchez, Guri Skeie, Konstantinos K. Tsilidis, Gianluca Severi, Carlotta Sacerdote, Sjoerd G. Elias, José Ramón Quirós, Marie-Christine Boutron-Ruault, Salvatore Panico, Krasimira Aleksandrova, Rosario Tumino, Sophia Harlid, Elom K. Aglago, [Aleksandrova,K, Reichmann,R] Nutrition, Immunity and Metabolism Senior Scientist Group, Department of Nutrition and Gerontology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany. [Aleksandrova,K, Reichmann,R] Institute of Nutritional Science, University of Potsdam, Potsdam, Germany. [Aleksandrova,K] Department of Epidemiological Methods and Etiological Research, Leibniz Institute for Prevention Research and Epidemiology - BIPS, Bremen, Germany. [Kaaks,R, Hüsing,A] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Jenab,M, Weiderpass,E, Aglago,EK, Gunter,MJ] International Agency for Research on Cancer, World Health Organization, Lyon, France. [Bueno-de-Mesquita,HB] National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. [Bueno-de-Mesquita,HB, Cross,AJ, Tsilidis,KK, Riboli,E] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Dahm,CC] Department of Public Health, Aarhus University, Aarhus, Denmark. [Eriksen,AK, Tjønneland,A] Danish Cancer Society Research Center, Copenhagen, Denmark. [Artaud,F, Boutron-Ruault,MC, Severi,G] CESP, Faculté de Medicine, Université Paris-Saclay, Villejuif, France. [Artaud,F, Severi,G] Institut Gustave Roussy, Villejuif, France. [Severi,G] Dipartimento di Statistica, Informatica e Applicazioni 'G. Parenti' (DISIA), University of Florence, Florence, Italy. [Trichopoulou,A, Karakatsani,A, Peppa,E] Hellenic Health Foundation, Athens, Greece. [Karakatsani,A] 2nd Pulmonary Medicine Department, School of Medicine, National and Kapodistrian University of Athens, 'ATTIKON' University Hospital, Haidari, Greece. [Panico,S] EPIC Centre of Naples, Dipartimento di Medicina Clinica e Chirurgia, University of Naples Federico II, Naples, Italy. [Masala,G] 1Cancer Risk Factors and Lifestyle Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network – ISPRO, Florence, Italy. [Grioni,S] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy. [Sacerdote,C] Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention (CPO), Turin, Italy. [Tumino,R] Cancer Registry and Histopathology Department, Provincial Health Authority (ASP), Ragusa, Italy. [Elias,SG, May,AM] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands. [Borch,KB, Sandanger,TM, Skeie,G] Department of Community Medicine, Health Faculty, UiT-the Arctic university of Norway, Tromsø, Norway. [Sánchez,MJ] Escuela Andaluza de Salud Pública (EASP), Granada, Spain. [Sánchez,MJ] Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain. [Sánchez,MJ, Huerta,JM, Gurrea,AB, Amiano,P] Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. [Sánchez,MJ] Universidad de Granada, Granada, Spain. [Huerta,JM] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. [Sala,N] Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Translational Research Laboratory, Catalan Institute of Oncology (ICO), Barcelona, Spain. [Sala,N] Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain. [Gurrea,AB] Navarra Public Health Institute, Pamplona, Spain. [Gurrea,AB] Navarra Institute for Health Research (IdiSNA), Pamplona, Spain. [Quirós,JR] Public Health Directorate, Asturias, Spain. [Amiano,P] Ministry of Health of the Basque Government, Public Health Division of Gipuzkoa, Biodonostia Health Research Institute, Donostia-San Sebastian, Spain. [Berntsson,J] Department of Clinical Sciences, Division of Oncology and Pathology, Lund University, Lund, Sweden. [Drake,I] Department of Clinical Sciences in Malmö, Lund University, Lund, Sweden. [van Guelpen,B, Harlid,S] Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden. [van Guelpen,B] Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden. [Key,T] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK. [Tsilidis,KK] Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece., This work was supported by the German Research Foundation (DFG) (grant AL 1784/3-1), which funded the research position of Dr. Aleksandrova for organizing study conduct and analysis. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum (DKFZ) and Federal Ministry of Education and Research (BMBF) (Germany), Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), Health Research Fund (FIS), Instituto de salud Carlos III PI13/00061 to Granada, PI13/ 01162 to EPIC-Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236), Navarra and Catalonia (Catalan Institute of Oncology – ICO-IDIBELL) (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), and Cancer Research UK (C864/A14136 to EPIC-Norfolk and C8221/A19170 to EPICOxford), Medical Research Council (MR/N003284/1 and MC-UU_12015/1 to EPIC-Norfolk and MR/M012190/1 to EPIC-Oxford) (United Kingdom). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Open Access funding enabled and organized by Projekt DEAL.
Subjects: Male, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Statistics as Topic::Probability::Risk::Risk Assessment [Medical Subject Headings], lcsh:Medicine, Cancer prevention, Cohort Studies, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Calibration [Medical Subject Headings], 0302 clinical medicine, Risk Factors, Neoplasias colorrectales, Medicine, 030212 general & internal medicine, Prospective Studies, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Nutritional Status [Medical Subject Headings], 10. No inequality, Prospective cohort study, 11 Medical and Health Sciences, Framingham Risk Score, Risk screening, Lifestyle behaviour, Risk prediction, Colorectal cancer, Public Health, Global Health, Social Medicine and Epidemiology, General Medicine, Middle Aged, 3. Good health, European Prospective Investigation into Cancer and Nutrition, 030220 oncology & carcinogenesis, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Prospective Studies [Medical Subject Headings], Female, Risk assessment, Colorectal Neoplasms, Research Article, Cohort study, Estils de vida, Waist, Lifestyles, Nutritional Status, Check Tags::Male [Medical Subject Headings], Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings], Estil de vida, Risk Assessment, Riesgo, Estilo de vida, 03 medical and health sciences, Càncer colorectal, General & Internal Medicine, Humans, Life Style, business.industry, lcsh:R, Health Care::Health Care Quality, Access, and Evaluation::Quality of Health Care::Health Care Evaluation Mechanisms::Statistics as Topic::Probability::Risk [Medical Subject Headings], Technology and Food and Beverages::Food and Beverages::Food::Vegetables [Medical Subject Headings], Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings], Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [Medical Subject Headings], Psychiatry and Psychology::Behavior and Behavior Mechanisms::Psychology, Social::Life Style [Medical Subject Headings], Nomogram, Lifestyle, Diet, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Check Tags::Female [Medical Subject Headings], Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Musculoskeletal Physiological Phenomena::Musculoskeletal Physiological Processes::Movement::Motor Activity::Exercise [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], business, Prevención de Enfermedades, Demography
Abstract: Background: Nutrition and lifestyle have been long established as risk factors for colorectal cancer (CRC). Modifiable lifestyle behaviours bear potential to minimize long-term CRC risk; however, translation of lifestyle information into individualized CRC risk assessment has not been implemented. Lifestyle-based risk models may aid the identification of high-risk individuals, guide referral to screening and motivate behaviour change. We therefore developed and validated a lifestyle-based CRC risk prediction algorithm in an asymptomatic European population. Methods: The model was based on data from 255,482 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study aged 19 to 70 years who were free of cancer at study baseline (1992–2000) and were followed up to 31 September 2010. The model was validated in a sample comprising 74,403 participants selected among five EPIC centres. Over a median follow-up time of 15 years, there were 3645 and 981 colorectal cancer cases in the derivation and validation samples, respectively. Variable selection algorithms in Cox proportional hazard regression and random survival forest (RSF) were used to identify the best predictors among plausible predictor variables. Measures of discrimination and calibration were calculated in derivation and validation samples. To facilitate model communication, a nomogram and a web-based application were developed. Results: The final selection model included age, waist circumference, height, smoking, alcohol consumption, physical activity, vegetables, dairy products, processed meat, and sugar and confectionary. The risk score demonstrated good discrimination overall and in sex-specific models. Harrell’s C-index was 0.710 in the derivation cohort and 0.714 in the validation cohort. The model was well calibrated and showed strong agreement between predicted and observed risk. Random survival forest analysis suggested high model robustness. Beyond age, lifestyle data led to improved model performance overall (continuous net reclassification improvement = 0.307 (95% CI 0.264–0.352)), and especially for young individuals below 45 years (continuous net reclassification improvement = 0.364 (95% CI 0.084–0.575)). Conclusions: LiFeCRC score based on age and lifestyle data accurately identifies individuals at risk for incident colorectal cancer in European populations and could contribute to improved prevention through motivating lifestyle change at an individual level., German Research Foundation (DFG) AL 1784/3-1, European Commission European Commission Joint Research Centre, International Agency for Research on Cancer, Danish Cancer Society, Ligue Contre le Cancer (France), Institut Gustave Roussy (France), Mutuelle Generale de l'Education Nationale (France), Institut National de la Sante et de la Recherche Medicale (Inserm), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum (DKFZ) (Germany), Federal Ministry of Education & Research (BMBF), Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro (AIRC), Consiglio Nazionale delle Ricerche (CNR), Netherlands Government, World Cancer Research Fund International (WCRF), Instituto de Salud Carlos III PI13/00061 PI13/01162, Junta de Andalucia, Regional Government of Asturias (Spain), Regional Government of Basque Country (Spain), Regional Government of Murcia (Spain) 6236, Regional Government of Navarra (Spain), Regional Government of Catalonia (Catalan Institute of Oncology -ICO-IDIBELL) (Spain), Swedish Cancer Society, Swedish Research Council, County Council of Skane (Sweden), County Council of Vasterbotten (Sweden), Cancer Research UK C864/A14136 C8221/A19170, UK Research & Innovation (UKRI) Medical Research Council UK (MRC) MR/N003284/1 MC-UU_12015/1 MR/M012190/1, Projekt DEAL
Published: 2021

11. Dietary Folate Intake and Breast Cancer Risk: European Prospective Investigation Into Cancer and Nutrition

Author: de Batlle, J., Ferrari, P., Chajes, V., Park, J. Y., Slimani, N., McKenzie, F., Overvad, K., Roswall, N., Tjønneland, A., Boutron-Ruault, M. C., Clavel-Chapelon, F., Fagherazzi, G., Katzke, V., Kaaks, R., Bergmann, M. M., Trichopoulou, A., Lagiou, P., Trichopoulos, D., Palli, D., Sieri, S., Panico, S., Tumino, R., Vineis, P., Bueno-de-Mesquita, H. B., Peeters, P. H., Hjartåker, A., Engeset, D., Weiderpass, E., Sánchez, S., Travier, N., Sánchez, M. J., Amiano, P., Chirlaque, M. D., Barricarte Gurrea, A., Khaw, K. T., Key, T. J., Bradbury, K. E., Ericson, U., Sonestedt, E., Van Guelpen, B., Schneede, J., Riboli, E., and Romieu, I.
Published: 2015
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12. Fatal pneumonia by Legionella in a farmer with hypersensitivity pneumonitis Neumonía por Legionella con desenlace fatal en un granjero con neumonitis por hipersensibilidad

Author: Vega García López, Elena Ordoqui García, Teresa Ferrer Gimeno, Jacinto Irisarri Orta, Marta García Esteban, and Aurelio Barricarte Gurrea
Subjects: Alveolitis alérgica extrínseca, factores de riesgo, Enfermedad del Legionario, subdeclaración, enfermedad relacionada con el trabajo, Allergic extrinsic alveolitis, risk factors, Legionnaires' disease, underreport, work-related disease, Medicine, Internal medicine, RC31-1245, Industrial medicine. Industrial hygiene, RC963-969
Abstract: Background: The retrospective investigation of a fatal sporadic Legionnaires' disease identified an unknown case of occupational hypersensitivity pneumonitis in a swine breeder. Methods: Chest high-resolution computed tomography, bronchoalveolar lavage, lung biopsy, arterial gasometry, pulmonary function tests and autopsy were performed. It was studied the presence of Legionella by serology and risk water samples were analyzed to identify the Legionella's source. Results: HP and Legionella pneumophila pneumonia diagnostics were confirmed. Lung fibrosis, a restrictive functional pattern, decreased diffusion, hypoxemia and bronchoalveolar lavage lymphocytosis were evidenced. Legionella´s source was detected in a shower and a positive serology in the patient. Autopsy verified pulmonary fibrosis and the septic shock leaded to Legionella causing the death. Conclusions: Chronic cough and pulmonary infiltrates in a farmer should suspect the presence of hypersensitivity pneumonitis. Later diagnosis carries a worse prognosis, the offending antigens exposure can't be avoided and fibrotic stage enhanced opportunity infection disease.Introducción: La investigación retrospectiva sobre un fallecimiento aislado por Legionelosis, hizo aflorar un caso de neumonitis por hipersensibilidad en un granjero cuidador de cerdos. Métodos: Se realizaron las siguientes pruebas: tomografía axial computerizada de alta resolución, lavado broncoalveolar, biopsia pulmonar, gasometría arterial, pruebas de función respiratoria y autopsia. Se estudió la presencia de Legionella por serología y se analizaron las muestras de fuentes de riesgo para identificar el foco de Legionella. Resultados: El estudio confirmó los diagnósticos de neumonitis por hipersensibilidad y neumonía por Legionella pneumophila. Las pruebas realizadas objetivaron la fibrosis pulmonar, un patrón respiratorio funcional restrictivo, un descenso de la difusión pulmonar, hipoxemia y la presencia de linfocitosis en el lavado broncoalveolar. Se detectó el foco de Legionella en una ducha y la serología fue positiva en el paciente. La autopsia confirmó la fibrosis pulmonar y el shock séptico por Legionella que causó la muerte. Conclusiones: La presencia de tos crónica e infiltrados pulmonares en un granjero debería hacer sospechar la existencia de una neumonitis por hipersensibilidad. Retrasar su diagnóstico conlleva un peor pronóstico, impide evitar la exposición a los antígenos causantes del cuadro y permite el avance de la fibrosis pulmonar facilitando la aparición de infecciones oportunistas.
Published: 2009

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

Author: Mao, Ziling, primary, Aglago, Elom K., additional, Zhao, Zhiwei, additional, Schalkwijk, Casper, additional, Jiao, Li, additional, Freisling, Heinz, additional, Weiderpass, Elisabete, additional, Hughes, David J., additional, Eriksen, Anne Kirstine, additional, Tjønneland, Anne, additional, Severi, Gianluca, additional, Rothwell, Joseph, additional, Boutron-Ruault, Marie-Christine, additional, Katzke, Verena, additional, Kaaks, Rudolf, additional, Schulze, Matthias B., additional, Birukov, Anna, additional, Krogh, Vittorio, additional, Panico, Salvatore, additional, Tumino, Rosario, additional, Ricceri, Fulvio, additional, Bueno-de-Mesquita, H. Bas, additional, Vermeulen, Roel C. H., additional, Gram, Inger T., additional, Skeie, Guri, additional, Sandanger, Torkjel M., additional, Quirós, J. Ramón, additional, Crous-Bou, Marta, additional, Sánchez, Maria-Jose, additional, Amiano, Pilar, additional, Chirlaque, María-Dolores, additional, Barricarte Gurrea, Aurelio, additional, Manjer, Jonas, additional, Johansson, Ingegerd, additional, Perez-Cornago, Aurora, additional, Jenab, Mazda, additional, and Fedirko, Veronika, additional
Published: 2021
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14. Evidence Update on the Relationship between Diet and the Most Common Cancers from the European Prospective Investigation into Cancer and Nutrition (EPIC) Study: A Systematic Review

Author: Miguel Rodríguez-Barranco, Dafina Petrova, Antonio Agudo, Ana Ching-López, María Dolores Chirlaque, Esther Molina-Montes, Pilar Amiano, Aurelio Barricarte-Gurrea, Esther Ubago-Guisado, and María José Sánchez
Subjects: vegetables, Oncology, medicine.medical_specialty, Meat, Mediterranean diet, Colorectal cancer, colorectal cancer, fruits, Fruits, meat, Prostate cancer, breast cancer, Breast cancer, Neoplasms, Internal medicine, Vegetables, medicine, Humans, TX341-641, Nutritional Physiological Phenomena, Prospective Studies, Lung cancer, Prospective cohort study, Càncer, Cancer, fish, Nutrition and Dietetics, Cancer prevention, Nutrition. Foods and food supply, alcohol, business.industry, prostate cancer, medicine.disease, European Prospective Investigation into Cancer and Nutrition, Diet, Europe, Alimentació, lung cancer, Fish, Intake, Systematic Review, Alcohol, business, intake, Food Science
Abstract: FundingE.U.-G. is supported by the Programa Operativo Fondo Social Europeo (FSE) de Andalucia (20142020) and Junta de Andalucia (reference DOC_01618)., The European Prospective Investigation into Cancer and Nutrition (EPIC) is a multicentre prospective study conducted in 23 centres in 10 European countries. Here we review the findings from EPIC on the relationship between diet-related exposures and incidence or mortality from the four most frequent cancers in the European population: colorectal, breast, lung, and prostate cancer. We conducted a systematic review following PRISMA guidelines and identified 110 high-quality studies based on the EPIC cohort. Fruit and vegetable consumption had a protective effect against colorectal, breast, and lung cancer, whereas only fruit had a protective effect against prostate cancer. A higher consumption of fish and lower consumption of red and processed meat were related with a lower risk of colorectal cancer; and higher consumption of fatty fish with lower risk of breast cancer. Calcium and yogurt intake were found to protect against colorectal and prostate cancer. Alcohol consumption increased the risk for colorectal and breast cancer. Finally, adherence to the Mediterranean diet emerged as a protective factor for colorectal and breast cancer. The EPIC study results are in agreement with the latest evidence from leading authorities on cancer prevention and help to inform public prevention policies and strategies., Programa Operativo Fondo Social Europeo (FSE) de Andalucia (20142020), Junta de Andalucia DOC_01618
Published: 2021

15. Evidence Update on the Relationship between Diet and the Most Common Cancers from the European Prospective Investigation into Cancer and Nutrition (EPIC) Study: A Systematic Review

Author: Ubago-Guisado, Esther, Rodríguez-Barranco, Miguel, Ching-López, Ana, Petrova, Dafina, Molina-Montes, Esther, Amiano, Pilar, Barricarte-Gurrea, Aurelio, Chirlaque, María-Dolores, Agudo, Antonio, Sánchez, María-José, [Ubago-Guisado,E, Rodríguez-Barranco,M, Ching-López,A, Petrova,D, Sánchez,MJ] Cancer Registry of Granada, Escuela Andaluza de Salud Pública, Granada, Spain. [Ubago-Guisado,E, Molina-Montes,E, Amiano,P, Barricarte-Gurrea,A, Chirlaque,MD, Sánchez,MJ] Epidemiology and Control of Chronic Diseases, CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain. [Ubago-Guisado,E, Sánchez,MJ] Cancer Epidemiology Group, Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain. [Petrova,D] Department of Experimental Psychology, Mind, Brain and Behavior Research Center (CIMCYC), University of Granada, Granada, Spain. [Molina-Montes,E] Department of Nutrition and Food Science, Campus of Cartuja, University of Granada, Granada, Spain. [Molina-Montes,E] Institute of Nutrition and Food Technology (INYTA) ‘José Mataix’, Biomedical Research Centre, University of Granada, Granada, Spain. [Amiano,P] Public Health Division of Gipuzkoa, BioDonostia Research Institute, Donostia-San Sebastian, Spain. [Barricarte-Gurrea,A] Navarra Public Health Institute, Pamplona, Spain. [Barricarte-Gurrea,A] Navarra Institute for Health Research (IdiSNA), Pamplona, Spain. [Chirlaque,MD] Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia University, Murcia, Spain. [Agudo,A] Unit of Nutrition and Cancer, Catalan Institute of Oncology, L’Hospitalet de Llobregat, Spain. [Agudo,A] Nutrition and Cancer Group, Epidemiology, Public Health, Cancer Prevention and Palliative Care Program, Bellvitge Biomedical Research Institute—IDIBELL, L’Hospitalet de Llobregat, Spain. [Sánchez,MJ] Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain., and E.U.-G. is supported by the Programa Operativo Fondo Social Europeo (FSE) de Andalucía (2014–2020) and Junta de Andalucía (reference DOC_01618).
Subjects: Metaanalisis, Frutas, Meat, Neoplasias de la próstata, Neoplasias pulmonares, Etanol, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings], Diseases::Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms [Medical Subject Headings], Carne, Fruits, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Ingestión de alimentos, Diseases::Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Genital Neoplasms, Male::Prostatic Neoplasms [Medical Subject Headings], Breast cancer, Neoplasias colorrectales, Vegetables, Prospective Studies, Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings], Prostate cancer, Revisión sistemática, Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [Medical Subject Headings], Diseases::Neoplasms [Medical Subject Headings], Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena [Medical Subject Headings], Colorectal cancer, Fish, Verduras, Neoplasias de la mama, Intake, Geographical Locations::Geographic Locations::Europe [Medical Subject Headings], Lung cancer, Alcohol
Abstract: The European Prospective Investigation into Cancer and Nutrition (EPIC) is a multicentre prospective study conducted in 23 centres in 10 European countries. Here we review the findings from EPIC on the relationship between diet-related exposures and incidence or mortality from the four most frequent cancers in the European population: colorectal, breast, lung, and prostate cancer. We conducted a systematic review following PRISMA guidelines and identified 110 high-quality studies based on the EPIC cohort. Fruit and vegetable consumption had a protective effect against colorectal, breast, and lung cancer, whereas only fruit had a protective effect against prostate cancer. A higher consumption of fish and lower consumption of red and processed meat were related with a lower risk of colorectal cancer; and higher consumption of fatty fish with lower risk of breast cancer. Calcium and yogurt intake were found to protect against colorectal and prostate cancer. Alcohol consumption increased the risk for colorectal and breast cancer. Finally, adherence to the Mediterranean diet emerged as a protective factor for colorectal and breast cancer. The EPIC study results are in agreement with the latest evidence from leading authorities on cancer prevention and help to inform public prevention policies and strategies. Yes
Published: 2021

16. Dietary advanced glycation end-products and colorectal cancer risk in the European prospective investigation into cancer and nutrition (EPIC) study

Author: J. Ramón Quirós, Elom K. Aglago, Marie-Christine Boutron-Ruault, Sabina Sieri, Bas Bueno-de-Mesquita, Rosario Tumino, Ingegerd Johansson, Maria Santucci de Magistris, Anne Kirstine Eriksen, Viktoria Knaze, Alicia K Heath, Aurora Perez-Cornago, Pilar Amiano, Anne Tjønneland, Joseph A. Rothwell, Verena Katzke, Elisabete Weiderpass, Casper G. Schalkwijk, Guri Skeie, Matthias B. Schulze, Ana Lucia Mayén, Rudolf Kaaks, Li Jiao, Anna Birukov, Jeroen W.G. Derksen, Jonas Manjer, María Dolores Chirlaque, Fulvio Ricceri, Leila Lujan-Barroso, Veronika Fedirko, Mazda Jenab, Aurelio Barricarte Gurrea, Gianluca Severi, Heinz Freisling, Torkjel M. Sandanger, Domenico Palli, Marc J. Gunter, Inger T. Gram, David J. Hughes, María José Sánchez, Interne Geneeskunde, and RS: Carim - V01 Vascular complications of diabetes and metabolic syndrome
Subjects: Oncology, Glycation End Products, Advanced, Male, Colorectal cancer, Eating, Glycation, Medicine, Advanced glycation end-products, Dietary exposure, Dietary glycation compounds, Adult, Aged, Colorectal Neoplasms, Diet, Diet Surveys, Europe, Female, Humans, Middle Aged, Proportional Hazards Models, Prospective Studies, Risk Assessment, TX341-641, Prospective cohort study, FOODS, Nutrition and Dietetics, Hazard ratio, European Prospective Investigation into Cancer and Nutrition, Näringslära, dietary exposure, Avaluació de l'estat nutricional, Epic study, Nutritional status measurement, SOLUBLE RECEPTOR, medicine.medical_specialty, DATABASE, Glycation End Products, colorectal cancer, ENDPRODUCTS, GUIDE, Article, dietary glycation compounds, advanced glycation end-products, Càncer colorectal, Internal medicine, Cancer och onkologi, Proportional hazards model, business.industry, Nutrition. Foods and food supply, medicine.disease, Confidence interval, Cancer and Oncology, CASEIN, Advanced, 1111 Nutrition and Dietetics, business, 0908 Food Sciences, Food Science
Abstract: This work was funded by the Wereld Kanker Onderzoek Fonds (WKOF), as part of the World Cancer Research Fund (WCRF) International grant program (WCRF 2015-1391, P.I. Mazda Jenab, International Agency for Research on Cancer). This work was partially financially supported by the Fondation de France (FDF grant no. 00081166 to H. Freisling and FDF grant no. 00089811 to A.-L. Mayen). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., The authors would like to thank the EPIC study participants and staff for their valuable contribution to this research. The authors would also like to thank Bertrand Hemon for the preparation of the databases. The coordination of EPIC is financially supported by the Inter national Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by: Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), German Insti tute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany); Associazione Italiana per la Ricerca sul Cancro (AIRC), Compagnia di San Paolo, and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS), Instituto de Salud Carlos III (ISCIII), Regional Govern ments of Andalucía, Asturias, the Basque Country, Murcia, and Navarra, and the Catalan Institute of Oncology (ICO) (Spain); Swedish Cancer Society, Swedish Research Council, and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C8221/A29017 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford) (United Kingdom). We are grateful to all of the participants who have been part of the project and to the many members of the study teams at the University of Cambridge who have enabled this research. We acknowledge the use of data from the EPIC-Aarhus cohort, PI Kim Overvad. We thank the CERCA Programme/Generalitat de Catalunya for institutional support., Dietary advanced glycation end-products (dAGEs) have been hypothesized to be associated with a higher risk of colorectal cancer (CRC) by promoting inflammation, metabolic dysfunction, and oxidative stress in the colonic epithelium. However, evidence from prospective cohort studies is scarce and inconclusive. We evaluated CRC risk associated with the intake of dAGEs in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Dietary intakes of three major dAGEs: N-epsilon-carboxy-methyllysine (CML), N-epsilon-carboxyethyllysine (CEL), and N-delta-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) were estimated in 450,111 participants (median follow-up = 13 years, with 6162 CRC cases) by matching to a detailed published European food composition database. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of dAGEs with CRC were computed using multivariable-adjusted Cox regression models. Inverse CRC risk associations were observed for CML (HR comparing extreme quintiles: HRQ5vs.(Q1) = 0.92, 95% CI = 0.85-1.00) and MG-H1 (HRQ5vs.(Q1) = 0.92, 95% CI = 0.85-1.00), but not for CEL (HRQ5vs.(Q1) = 0.97, 95% CI = 0.89-1.05). The associations did not differ by sex or anatomical location of the tumor. Contrary to the initial hypothesis, our findings suggest an inverse association between dAGEs and CRC risk. More research is required to verify these findings and better differentiate the role of dAGEs from that of endogenously produced AGEs and their precursor compounds in CRC development., Wereld Kanker Onderzoek Fonds (WKOF), World Cancer Research Fund (WCRF) International grant program (WCRF) 2015-1391, Fondation de France 00081166- 00089811
Published: 2021

17. Soft Drink and Juice Consumption and Renal Cell Carcinoma Incidence and Mortality in the European Prospective Investigation into Cancer and Nutrition

Author: Guri Skeie, Leila Lujan-Barroso, Inge Huybrechts, Bernard Srour, Nick P Jayanth, David C. Muller, Vittorio Krogh, Pilar Amiano, Rosario Tumino, Stina Ramne, Matthias B. Schulze, Kim Overvad, Anne Tjønneland, Alberto Catalano, Fabrizio Pasanisi, Mazda Jenab, Aurelio Barricarte Gurrea, Karina Standahl Olsen, Carmen Santiuste, Håkan Axelson, Giovanna Masala, Kristina E.N. Petersen, Elio Riboli, Eleanor L. Watts, Verena Katzke, Joanna L Clasen, Miguel Rodríguez-Barranco, Alicia K Heath, Magritt Brustad, Manuela M. Bergmann, Börje Ljungberg, Elisabete Weiderpass, Cancer Research UK, Heath, A. K., Clasen, J. L., Jayanth, N. P., Jenab, M., Tjonneland, A., Petersen, K. E. N., Overvad, K., Srour, B., Katzke, V., Bergmann, M. M., Schulze, M. B., Masala, G., Krogh, V., Tumino, R., Catalano, A., Pasanisi, F., Brustad, M., Olsen, K. S., Skeie, G., Lujan-Barroso, L., Rodriguez-Barranco, M., Amiano, P., Santiuste, C., Gurrea, A. B., Axelson, H., Ramne, S., Ljungberg, B., Watts, E. L., Huybrechts, I., Weiderpass, E., Riboli, E., and Muller, D. C.
Subjects: Male, 0301 basic medicine, Epidemiology, Carbonated Beverages, urologic and male genital diseases, Carbonated Beverages/adverse effects, Body Mass Index, 0302 clinical medicine, soft drinks, Risk Factors, Renal cell carcinoma, sweetened beverages, Medicine, Prospective Studies, 11 Medical and Health Sciences, Diet Surveys/statistics & numerical data, RISK, Kidney Neoplasms/epidemiology, Incidence, Incidence (epidemiology), kidney cancer, Middle Aged, Kidney Neoplasms, European Prospective Investigation into Cancer and Nutrition, Europe, Fruit and Vegetable Juices, Oncology, 030220 oncology & carcinogenesis, Female, Adult, renal cell carcinoma, medicine.medical_specialty, Diet Surveys, juice, Article, Europe/epidemiology, 03 medical and health sciences, Internal medicine, Humans, Obesity, Risk factor, Carcinoma, Renal Cell, Aged, Carcinoma, Renal Cell/epidemiology, Proportional hazards model, business.industry, Sweetening Agents/adverse effects, Feeding Behavior, Obesity/epidemiology, medicine.disease, Confidence interval, Fruit and Vegetable Juices/adverse effects, 030104 developmental biology, Sweetening Agents, business, Body mass index, Follow-Up Studies
Abstract: Background: Renal cell carcinoma (RCC) accounts for more than 80% of kidney cancers in adults, and obesity is a known risk factor. Regular consumption of sweetened beverages has been linked to obesity and several chronic diseases, including some types of cancer. It is uncertain whether soft drink and juice consumption is associated with risk of RCC. We investigated the associations of soft drink and juice consumption with RCC incidence and mortality in the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods: A total of 389,220 EPIC participants with median age of 52 years at recruitment (1991–2000) were included. Cox regression yielded adjusted HRs and 95% confidence intervals (CI) for RCC incidence and mortality in relation to intakes of juices and total, sugar-sweetened, and artificially sweetened soft drinks. Results: A total of 888 incident RCCs and 356 RCC deaths were identified. In models including adjustment for body mass index and energy intake, there was no higher risk of incident RCC associated with consumption of juices (HR per 100 g/day increment = 1.03; 95% CI, 0.97–1.09), total soft drinks (HR = 1.01; 95% CI, 0.98–1.05), sugar-sweetened soft drinks (HR = 0.99; 95% CI, 0.94–1.05), or artificially sweetened soft drinks (HR = 1.02; 95% CI, 0.96–1.08). In these fully adjusted models, none of the beverages was associated with RCC mortality (HR, 95% CI per 100 g/day increment 1.06, 0.97–1.16; 1.03, 0.98–1.09; 0.97, 0.89–1.07; and 1.06, 0.99–1.14, respectively). Conclusions: Consumption of juices or soft drinks was not associated with RCC incidence or mortality after adjusting for obesity. Impact: Soft drink and juice intakes are unlikely to play an independent role in RCC development or mortality.
Published: 2021

18. Plasma concentrations of advanced glycation end-products and colorectal cancer risk in the EPIC study

Author: Vittorio Simeon, Ana-Lucia Mayén, Anne Tjønneland, Aurora Perez-Cornago, Giovanna Masala, Christina C. Dahm, Sabina Sieri, Elisabete Weiderpass, Heinz Freisling, Paula Jakszyn, Alicia K Heath, Li Jiao, Mazda Jenab, Pilar Amiano, Aurelio Barricarte Gurrea, Theron Johnson, Alessandra Macciotta, David J. Hughes, Anja Olsen, Guri Skeie, Torkjel M. Sandanger, Matthias B. Schulze, Veronika Fedirko, Krasimira Aleksandrova, Rosario Tumino, Verena Katzke, Sandra Colorado-Yohar, Elom K. Aglago, Casper G. Schalkwijk, Bas Bueno-de-Mesquita, María José Sánchez, Marc J. Gunter, Inger T. Gram, Interne Geneeskunde, RS: Carim - V01 Vascular complications of diabetes and metabolic syndrome, Aglago, E. K., Schalkwijk, C. G., Freisling, H., Fedirko, V., Hughes, D. J., Jiao, L., Dahm, C. C., Olsen, A., Tjonneland, A., Katzke, V., Johnson, T., Schulze, M. B., Aleksandrova, K., Masala, G., Sieri, S., Simeon, V., Tumino, R., Macciotta, A., Bueno-De-Mesquita, B., Skeie, G., Gram, I. T., Sandanger, T., Jakszyn, P., Sanchez, M. -J., Amiano, P., Colorado-Yohar, S. M., Gurrea, A. B., Perez-Cornago, A., Mayen, A. -L., Weiderpass, E., Gunter, M. J., Heath, A. K., and Jenab, M.
Subjects: 0301 basic medicine, Glycation End Products, Advanced, Male, Ornithine, Cancer Research, STRESS, Colorectal cancer, Gastroenterology, Cohort Studies, chemistry.chemical_compound, 0302 clinical medicine, Glycation, Tandem Mass Spectrometry, Odds Ratio, Medicine, Cancer Biomarkers and Molecular Epidemiology, Imidazoles, General Medicine, Middle Aged, glycotoxin, 030220 oncology & carcinogenesis, METHYLGLYOXAL, Plasma concentration, Cohort, Advanced glycation end-product, Epic study, Female, Colorectal Neoplasms, Adult, SOLUBLE RECEPTOR, EXPRESSION, medicine.medical_specialty, colorectal cancer, 03 medical and health sciences, AGE, FOOD, Internal medicine, Humans, Genetic Predisposition to Disease, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, Genetic Association Studies, Aged, business.industry, Lysine, RECOGNITION, advanced glycation end-product, Odds ratio, medicine.disease, Confidence interval, 030104 developmental biology, chemistry, business, Chromatography, Liquid
Abstract: This is a pre-copyedited, author-produced version of an article accepted for publication in Carcinogenesis following peer review. The version of record Aglago, Schalkwijk, Freisling, Fedirko, Hughes, Jiao, Dahm, Olsen, Tjønneland, Katzke, Johnson, Schulze, Aleksandrova, Masala, Sieri, Simeon, Tumino, Macciotta, Bueno-De-Mesquita, Skeie, Gram, Sandanger, Jakszyn, Sánchez, Amiano, Colorado-Yohar, Barricarte, Perez-Cornago, Mayén, Weiderpass, Gunter, Heath, Jenab. Plasma concentrations of advanced glycation end-products and colorectal cancer risk in the EPIC study. Carcinogenesis. 2021;42(5):705-713 is available online at: https://doi.org/10.1093/carcin/bgab026. Advanced glycation end-products (AGEs) are a heterogeneous group of compounds formed by the non-enzymatic reaction between amino acids and reducing sugars, or dicarbonyls as intermediate compounds. Experimental studies suggest that AGEs may promote colorectal cancer, but prospective epidemiologic studies are inconclusive. We conducted a case–control study nested within a large European cohort. Plasma concentrations of three protein-bound AGEs—Nε-(carboxy-methyl)lysine (CML), Nε-(carboxy-ethyl)lysine (CEL) and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1)—were measured by ultra-performance liquid chromatography–tandem mass spectrometry in baseline samples collected from 1378 incident primary colorectal cancer cases and 1378 matched controls. Multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were computed using conditional logistic regression for colorectal cancer risk associated with CML, CEL, MG-H1, total AGEs, and [CEL+MG-H1: CML] and [CEL:MG-H1] ratios. Inverse colorectal cancer risk associations were observed for CML (OR comparing highest to lowest quintile, ORQ5 versus Q1 = 0.40, 95% CI: 0.27–0.59), MG-H1 (ORQ5 versus Q1 = 0.73, 95% CI: 0.53–1.00) and total AGEs (OR Q5 versus Q1 = 0.52, 95% CI: 0.37–0.73), whereas no association was observed for CEL. A higher [CEL+MG-H1: CML] ratio was associated with colorectal cancer risk (ORQ5 versus Q1 = 1.91, 95% CI: 1.31–2.79). The associations observed did not differ by sex, or by tumour anatomical sub-site. Although individual AGEs concentrations appear to be inversely associated with colorectal cancer risk, a higher ratio of methylglyoxal-derived AGEs versus those derived from glyoxal (calculated by [CEL+MG-H1: CML] ratio) showed a strong positive risk association. Further insight on the metabolism of AGEs and their dicarbonyls precursors, and their roles in colorectal cancer development is needed.
Published: 2021

19. Evidence Update on the Relationship between Diet and the Most Common Cancers from the European Prospective Investigation into Cancer and Nutrition (EPIC) Study: A Systematic Review

Author: Ubago-Guisado, Esther, primary, Rodríguez-Barranco, Miguel, additional, Ching-López, Ana, additional, Petrova, Dafina, additional, Molina-Montes, Esther, additional, Amiano, Pilar, additional, Barricarte-Gurrea, Aurelio, additional, Chirlaque, María-Dolores, additional, Agudo, Antonio, additional, and Sánchez, María-José, additional
Published: 2021
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20. Nutrient patterns and their food sources in an International Study Setting: report from the EPIC study.

Author: Aurelie Moskal, Pedro T Pisa, Pietro Ferrari, Graham Byrnes, Heinz Freisling, Marie-Christine Boutron-Ruault, Claire Cadeau, Laura Nailler, Andrea Wendt, Tilman Kühn, Heiner Boeing, Brian Buijsse, Anne Tjønneland, Jytte Halkjær, Christina C Dahm, Stephanie E Chiuve, Jose R Quirós, Genevieve Buckland, Esther Molina-Montes, Pilar Amiano, José M Huerta Castaño, Aurelio Barricarte Gurrea, Kay-Tee Khaw, Marleen A Lentjes, Timothy J Key, Dora Romaguera, Anne-Claire Vergnaud, Antonia Trichopoulou, Christina Bamia, Philippos Orfanos, Domenico Palli, Valeria Pala, Rosario Tumino, Carlotta Sacerdote, Maria Santucci de Magistris, H Bas Bueno-de-Mesquita, Marga C Ocké, Joline W J Beulens, Ulrika Ericson, Isabel Drake, Lena M Nilsson, Anna Winkvist, Elisabete Weiderpass, Anette Hjartåker, Elio Riboli, and Nadia Slimani
Subjects: Medicine, Science
Abstract: BACKGROUND:Compared to food patterns, nutrient patterns have been rarely used particularly at international level. We studied, in the context of a multi-center study with heterogeneous data, the methodological challenges regarding pattern analyses. METHODOLOGY/PRINCIPAL FINDINGS:We identified nutrient patterns from food frequency questionnaires (FFQ) in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study and used 24-hour dietary recall (24-HDR) data to validate and describe the nutrient patterns and their related food sources. Associations between lifestyle factors and the nutrient patterns were also examined. Principal component analysis (PCA) was applied on 23 nutrients derived from country-specific FFQ combining data from all EPIC centers (N = 477,312). Harmonized 24-HDRs available for a representative sample of the EPIC populations (N = 34,436) provided accurate mean group estimates of nutrients and foods by quintiles of pattern scores, presented graphically. An overall PCA combining all data captured a good proportion of the variance explained in each EPIC center. Four nutrient patterns were identified explaining 67% of the total variance: Principle component (PC) 1 was characterized by a high contribution of nutrients from plant food sources and a low contribution of nutrients from animal food sources; PC2 by a high contribution of micro-nutrients and proteins; PC3 was characterized by polyunsaturated fatty acids and vitamin D; PC4 was characterized by calcium, proteins, riboflavin, and phosphorus. The nutrients with high loadings on a particular pattern as derived from country-specific FFQ also showed high deviations in their mean EPIC intakes by quintiles of pattern scores when estimated from 24-HDR. Center and energy intake explained most of the variability in pattern scores. CONCLUSION/SIGNIFICANCE:The use of 24-HDR enabled internal validation and facilitated the interpretation of the nutrient patterns derived from FFQs in term of food sources. These outcomes open research opportunities and perspectives of using nutrient patterns in future studies particularly at international level.
Published: 2014
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21. 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

22. Soft drink and juice consumption and renal cell carcinoma incidence and mortality in the european prospective investigation into cancer and nutrition

Author: Heath, Alicia K., Clasen, Joanna L., Jayanth, Nick P., Jenab, Mazda, Tjønneland, Anne, Petersen, Kristina Elin Nielsen, Overvad, Kim, Srour, Bernard, Katzke, Verena, Bergmann, Manuela M., Schulze, Matthias B., Masala, Giovanna, Krogh, Vittorio, Tumino, Rosario, Catalano, Alberto, Pasanisi, Fabrizio, Brustad, Magritt, Standahl Olsen, Karina, Skeie, Guri, Lujan-Barroso, Leila, Rodríguez-Barranco, Miguel, Amiano, Pilar, Santiuste, Carmen, Barricarte Gurrea, Aurelio, Axelson, Hakan, Ramne, Stina, Ljungberg, Börje, Watts, Eleanor L., Huybrechts, Inge, Weiderpass, Elisabete, Riboli, Elio, Muller, David C., Heath, Alicia K., Clasen, Joanna L., Jayanth, Nick P., Jenab, Mazda, Tjønneland, Anne, Petersen, Kristina Elin Nielsen, Overvad, Kim, Srour, Bernard, Katzke, Verena, Bergmann, Manuela M., Schulze, Matthias B., Masala, Giovanna, Krogh, Vittorio, Tumino, Rosario, Catalano, Alberto, Pasanisi, Fabrizio, Brustad, Magritt, Standahl Olsen, Karina, Skeie, Guri, Lujan-Barroso, Leila, Rodríguez-Barranco, Miguel, Amiano, Pilar, Santiuste, Carmen, Barricarte Gurrea, Aurelio, Axelson, Hakan, Ramne, Stina, Ljungberg, Börje, Watts, Eleanor L., Huybrechts, Inge, Weiderpass, Elisabete, Riboli, Elio, and Muller, David C.
Abstract: Background: Renal cell carcinoma (RCC) accounts for more than 80% of kidney cancers in adults, and obesity is a known risk factor. Regular consumption of sweetened beverages has been linked to obesity and several chronic diseases, including some types of cancer. It is uncertain whether soft drink and juice consumption is associated with risk of RCC. We investigated the associations of soft drink and juice consumption with RCC incidence and mortality in the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods: A total of 389,220 EPIC participants with median age of 52 years at recruitment (1991-2000) were included. Cox regression yielded adjusted HRs and 95% confidence intervals (CI) for RCC incidence and mortality in relation to intakes of juices and total, sugar-sweetened, and artificially sweetened soft drinks. Results: A total of 888 incident RCCs and 356 RCC deaths were identified. In models including adjustment for body mass index and energy intake, there was no higher risk of incident RCC associated with consumption of juices (HR per 100 g/day increment ¼ 1.03; 95% CI, 0.97-1.09), total soft drinks (HR ¼ 1.01; 95% CI, 0.98-1.05), sugar-sweetened soft drinks (HR ¼ 0.99; 95% CI, 0.94-1.05), or artificially sweetened soft drinks (HR ¼ 1.02; 95% CI, 0.96-1.08). In these fully adjusted models, none of the beverages was associated with RCC mortality (HR, 95% CI per 100 g/day increment 1.06, 0.97-1.16; 1.03, 0.98-1.09; 0.97, 0.89-1.07; and 1.06, 0.99-1.14, respectively). Conclusions: Consumption of juices or soft drinks was not associated with RCC incidence or mortality after adjusting for obesity. Impact: Soft drink and juice intakes are unlikely to play an independent role in RCC development or mortality.
Published: 2021
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23. A Prospective Diet-Wide Association Study for Risk of Colorectal Cancer in EPIC

Author: Ingegerd Johansson, David S. Lopez, Alicia K Heath, Amanda J. Cross, Anne Tjønneland, J. Ramón Quirós, Melissa A. Merritt, Paula Jakszyn, Bas Bueno-de-Mesquita, Pilar Amiano, Anne Kirstine Eriksen, Manuela M. Bergmann, Marc J. Gunter, Bernard Srour, David C. Muller, Piet A. van den Brandt, Matthias B. Schulze, Salvatore Panico, Claudia Agnoli, Pietro Ferrari, Marco Lukic, José María Huerta, Christina C. Dahm, Therese Haugdahl Nøst, Areti Papadopoulou, Aurelio Barricarte Gurrea, Rosario Tumino, María José Sánchez, Fulvio Ricceri, Nadia Bastide, Paolo Vineis, Ulrika Ericson, Eva Ardanaz, Gianluca Severi, Guri Skeie, Aurora Perez-Cornago, Nikos Papadimitriou, Emmanouil Bouras, Elisabete Weiderpass, Ellio Riboli, Ioanna Tzoulaki, Heiner Boeing, Stina Bodén, Giovanna Masala, Jeroen W.G. Derksen, Jonna Berntsson, Verena Katzke, Elena Critselis, Konstantinos K. Tsilidis, University of Ioannina, Maastricht University [Maastricht], Imperial College London, Biomedical Research Foundation of the Academy of Athens (BRFAA), International Agency for Cancer Research (IACR), German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, University of Hawai'i [Honolulu] (UH), The University of Texas Health Science Center at Houston (UTHealth), University of Oxford [Oxford], University of Potsdam, The Arctic University of Norway (UiT), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Umeå University, Università degli studi di Torino = University of Turin (UNITO), Lund University [Lund], Instituto de Salud Carlos III [Madrid] (ISC), Aarhus University [Aarhus], IRCCS Istituto Nazionale dei Tumori [Milano], University of Copenhagen = Københavns Universitet (KU), National Institute for Public Health and the Environment [Bilthoven] (RIVM), University of Naples Federico II, La Salle [Ramon Llull University], Utrecht University [Utrecht], Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), Kræftens Bekæmpelse, DCS, Deutsches Krebsforschungszentrum, DKFZ, Centre International de Recherche sur le Cancer, CIRC, International Council of Ophthalmology, ICO, National Research Council, NRC, University of Maryland School of Public Health, SPH, Medical Research Council, MRC: MR/M012190/1, Cancer Research UK, CRUK: C8221/A29017, World Cancer Research Fund, WCRF: WCRF 2014/1180, Institut National de la Santé et de la Recherche Médicale, Inserm, Bundesministerium für Bildung und Forschung, BMBF, Cancerfonden, Ministerie van Volksgezondheid, Welzijn en Sport, VWS, Ligue Contre le Cancer, Vetenskapsrådet, VR, Instituto de Salud Carlos III, ISCIII, Associazione Italiana per la Ricerca sul Cancro, AIRC, Deutsche Krebshilfe, Institut Gustave-Roussy, Mutuelle Générale de l'Education Nationale, MGEN, Funding This work was supported by the World Cancer Research Fund International Regular Grant Programme (WCRF 2014/1180 to Konstantinos K. Tsilidis). The coordination of EPIC is financially supported by International Agency for Research on Cancer and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the National Institute for Health Research Imperial Biomedical Research Centre. The national cohorts are supported by the Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle G?n?rale de l'Education Nationale, Institut National de la Sant? et de la Recherche M?dicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), Health Research Fund (FIS)?Instituto de Salud Carlos III (ISCIII), Regional Governments of Andaluc?a, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology (ICO) (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Sk?ne and V?sterbotten (Sweden), and Cancer Research UK (14136 to EPIC-Norfolk, C8221/A29017 to EPIC-Oxford) and Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (United Kingdom). Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy, or views of the International Agency for Research on Cancer/World Health Organization., Funding This work was supported by the World Cancer Research Fund International Regular Grant Programme ( WCRF 2014/1180 to Konstantinos K. Tsilidis). The coordination of EPIC is financially supported by International Agency for Research on Cancer and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the National Institute for Health Research Imperial Biomedical Research Centre . The national cohorts are supported by the Danish Cancer Society (Denmark), Ligue Contre le Cancer , Institut Gustave Roussy , Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid , German Cancer Research Center ( DKFZ ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research ( BMBF ) (Germany), Dutch Ministry of Public Health , Welfare and Sports ( VWS ), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund ( WCRF ), Statistics Netherlands (The Netherlands), Health Research Fund (FIS)– Instituto de Salud Carlos III ( ISCIII ), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology ( ICO ) (Spain), Swedish Cancer Society , Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), Epidemiologie, and RS: GROW - R1 - Prevention
Subjects: medicine.medical_specialty, [SDV]Life Sciences [q-bio], Riboflavin, colorectal cancer, Lower risk, Cohort Studies, Animal science, beta-Carotene, Risk Factors, Epidemiology, medicine, cohort study, Humans, Prospective Studies, Hepatology, Gastroenterology & Hepatology, business.industry, Hazard ratio, Gastroenterology, food and beverages, 1103 Clinical Sciences, Confidence interval, European Prospective Investigation into Cancer and Nutrition, Diet, epidemiology, nutrition, business, Colorectal Neoplasms, Cohort study
Abstract: Background & Aims: Evidence regarding the association of dietary exposures with colorectal cancer (CRC) risk is not consistent with a few exceptions. Therefore, we conducted a diet-wide association study (DWAS) in the European Prospective Investigation into Cancer and Nutrition (EPIC) to evaluate the associations between several dietary exposures with CRC risk. Methods: The association of 92 food and nutrient intakes with CRC risk was assessed in 386,792 participants, 5069 of whom developed incident CRC. Correction for multiple comparisons was performed using the false discovery rate, and emerging associations were examined in the Netherlands Cohort Study (NLCS). Multiplicative gene-nutrient interactions were also tested in EPIC based on known CRC-associated loci. Results: In EPIC, alcohol, liquor/spirits, wine, beer/cider, soft drinks, and pork were positively associated with CRC, whereas milk, cheese, calcium, phosphorus, magnesium, potassium, riboflavin, vitamin B6, beta carotene, fruit, fiber, nonwhite bread, banana, and total protein intakes were inversely associated. Of these 20 associations, 13 were replicated in the NLCS, for which a meta-analysis was performed, namely alcohol (summary hazard ratio [HR] per 1-SD increment in intake: 1.07; 95% confidence interval [CI], 1.04–1.09), liquor/spirits (HR per 1-SD increment in intake, 1.04; 95% CI, 1.02–1.06), wine (HR per 1-SD increment in intake, 1.04; 95% CI, 1.02–1.07), beer/cider (HR per 1-SD increment in intake, 1.06; 95% CI, 1.04–1.08), milk (HR per 1-SD increment in intake, 0.95; 95% CI, 0.93–0.98), cheese (HR per 1-SD increment in intake, 0.96; 95% CI, 0.94–0.99), calcium (HR per 1-SD increment in intake, 0.93; 95% CI, 0.90–0.95), phosphorus (HR per 1-SD increment in intake, 0.92; 95% CI, 0.90–0.95), magnesium (HR per 1-SD increment in intake, 0.95; 95% CI, 0.92–0.98), potassium (HR per 1-SD increment in intake, 0.96; 95% CI, 0.94–0.99), riboflavin (HR per 1-SD increment in intake, 0.94; 95% CI, 0.92–0.97), beta carotene (HR per 1-SD increment in intake, 0.96; 95% CI, 0.93–0.98), and total protein (HR per 1-SD increment in intake, 0.94; 95% CI, 0.92–0.97). None of the gene-nutrient interactions were significant after adjustment for multiple comparisons. Conclusions: Our findings confirm a positive association for alcohol and an inverse association for dairy products and calcium with CRC risk, and also suggest a lower risk at higher dietary intakes of phosphorus, magnesium, potassium, riboflavin, beta carotene, and total protein.
Published: 2020

24. Lifestyle factors and serum androgens among 636 middle aged men from seven countries in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Author: Suzuki, Reiko, Allen, Naomi E., Appleby, Paul N., Key, Timothy J., Dossus, Laure, Tjønneland, Anne, Føns Johnsen, Nina, Overvad, Kim, Sacerdote, Carlotta, Palli, Domenico, Krogh, Vittorio, Tumino, Rosario, Rohrmann, Sabine, Linseisen, Jakob, Boeing, Heiner, Trichopoulou, Antonia, Makrygiannis, Georgios, Misirli, Gesthimani, Bueno-de-Mesquita, H. Bas, May, Anne M., Díaz, María José Tormo, Sánchez, Maria-José, Barricarte Gurrea, Aurelio, Rodríguez Suárez, Laudina, Buckland, Genevieve, Larrañaga, Nerea, Bingham, Sheila, Khaw, Kay-Tee, Rinaldi, Sabina, Slimani, Nadia, Jenab, Mazda, Riboli, Elio, and Kaaks, Rudolf
Published: 2009
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25. Ethanol intake and the risk of pancreatic cancer in the European prospective investigation into cancer and nutrition (EPIC)

Author: Rohrmann, Sabine, Linseisen, Jakob, Vrieling, Alina, Boffetta, Paolo, Stolzenberg-Solomon, Rachael Z., Lowenfels, Albert B., Jensen, Majken K., Overvad, Kim, Olsen, Anja, Tjonneland, Anne, Boutron-Ruault, Marie-Christine, Clavel-Chapelon, Francoise, Fagherazzi, G., Misirli, Gesthimani, Lagiou, Pagona, Trichopoulou, Antonia, Kaaks, Rudolf, Bergmann, Manuela M., Boeing, Heiner, Bingham, Sheila, Khaw, Kay-Tee, Allen, Naomi, Roddam, Andrew, Palli, Domenico, Pala, Valeria, Panico, Salvatore, Tumino, Rosario, Vineis, Paolo, Peeters, Petra H. M., Hjartåker, Anette, Lund, Eiliv, Cornejo, Ma Luisa Redondo, Agudo, Antonio, Arriola, Larraitz, Sánchez, Maria-José, Tormo, María-José, Barricarte Gurrea, Aurelio, Lindkvist, Björn, Manjer, Jonas, Johansson, Ingegerd, Ye, Weimin, Slimani, Nadia, Duell, Eric J., Jenab, Mazda, Michaud, Dominique S., Mouw, Traci, Riboli, Elio, and Bueno-de-Mesquita, H. Bas
Published: 2009
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26. Soft Drink and Juice Consumption and Renal Cell Carcinoma Incidence and Mortality in the European Prospective Investigation into Cancer and Nutrition

Author: Heath, Alicia K., primary, Clasen, Joanna L., additional, Jayanth, Nick P., additional, Jenab, Mazda, additional, Tjønneland, Anne, additional, Petersen, Kristina Elin Nielsen, additional, Overvad, Kim, additional, Srour, Bernard, additional, Katzke, Verena, additional, Bergmann, Manuela M., additional, Schulze, Matthias B., additional, Masala, Giovanna, additional, Krogh, Vittorio, additional, Tumino, Rosario, additional, Catalano, Alberto, additional, Pasanisi, Fabrizio, additional, Brustad, Magritt, additional, Olsen, Karina Standahl, additional, Skeie, Guri, additional, Luján-Barroso, Leila, additional, Rodríguez-Barranco, Miguel, additional, Amiano, Pilar, additional, Santiuste, Carmen, additional, Barricarte Gurrea, Aurelio, additional, Axelson, Håkan, additional, Ramne, Stina, additional, Ljungberg, Börje, additional, Watts, Eleanor L., additional, Huybrechts, Inge, additional, Weiderpass, Elisabete, additional, Riboli, Elio, additional, and Muller, David C., additional
Published: 2021
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27. A 584 bp deletion in CTRB2 inhibits chymotrypsin B2 activity and secretion and confers risk of pancreatic cancer

Author: Irene Collins, Federico Canzian, Katelyn Connelly, Loic LeMarchand, Harvey A. Risch, Salvatore Panico, Alison P. Klein, Sumeth Perera, Stephen J. Chanock, Mengmeng Du, Aurelio Barricarte Gurrea, Bas Bueno-de-Mesquita, Marc Thornquist, Gloria M. Petersen, Charles Kooperberg, Xiao-Ou Shu, Brian M. Wolpin, Ashley Jermusyk, Graham G. Giles, Núria Malats, Ulrike Peters, Ruth C. Travis, Phyllis J. Goodman, Jill P. Smith, Christopher J. Westlake, Donghui Li, Mattias Johansson, J. Michael Gaziano, Julie E. Buring, Francisco X. Real, Anne Tjønneland, Stephen Gallinger, Kala Visvanathan, Eric J. Jacobs, Naomi Gordon, Rachel E. Neale, Chen Yuan, Tongwu Zhang, Peter Kraft, Stephen K. Van Den Eeden, Laufey T. Amundadottir, Aidan O’Brien, Ehssan Abdolalizadeh, Jun Zhong, Wei Zheng, Jason W. Hoskins, Rachael Z. Stolzenberg-Solomon, Jianxin Shi, Paige M. Bracci, Laura Beane-Freeman, Daina Eiser, Malin Sund, Demetrius Albanes, and Alan A. Arslan
Subjects: Chymotrypsin, Genotype, Quantitative Trait Loci, Genome-wide association study, Biology, medicine.disease, Molecular biology, Polymorphism, Single Nucleotide, Exon skipping, Article, Pancreatic Neoplasms, Exon, Pancreatic cancer, Case-Control Studies, RNA splicing, Genetics, medicine, Unfolded protein response, biology.protein, Humans, Allele, Genetics (clinical), Genome-Wide Association Study, Sequence Deletion
Abstract: Genome-wide association studies (GWASs) have discovered 20 risk loci in the human genome where germline variants associate with risk of pancreatic ductal adenocarcinoma (PDAC) in populations of European ancestry. Here, we fine-mapped one such locus on chr16q23.1 (rs72802365, p = 2.51 × 10(−17), OR = 1.36, 95% CI = 1.31–1.40) and identified colocalization (PP = 0.87) with aberrant exon 5–7 CTRB2 splicing in pancreatic tissues (p(GTEx) = 1.40 × 10(−69), β(GTEx) = 1.99; p(LTG) = 1.02 × 10(−30), β(LTG) = 1.99). Imputation of a 584 bp structural variant overlapping exon 6 of CTRB2 into the GWAS datasets resulted in a highly significant association with pancreatic cancer risk (p = 2.83 × 10(−16), OR = 1.36, 95% CI = 1.31–1.42), indicating that it may underlie this signal. Exon skipping attributable to the deletion (risk) allele introduces a premature stop codon in exon 7 of CTRB2, yielding a truncated chymotrypsinogen B2 protein that lacks chymotrypsin activity, is poorly secreted, and accumulates intracellularly in the endoplasmic reticulum (ER). We propose that intracellular accumulation of a nonfunctional chymotrypsinogen B2 protein leads to ER stress and pancreatic inflammation, which may explain the increased pancreatic cancer risk in carriers of CTRB2 exon 6 deletion alleles.
Published: 2020

28. Theoretical potential for endometrial cancer prevention through primary risk factor modification: Estimates from the EPIC cohort

Author: Patrick Arveux, Elio Riboli, Carla H. van Gils, Marina Kvaskoff, Rudolf Kaaks, María José Sánchez, Kim Overvad, Pilar Amiano, Naomi E. Allen, Elisabete Weiderpass, Christina C. Dahm, Catalina Bonet, Carlo La Vecchia, Giovanna Masala, Amalia Mattiello, José Ramón Quirós, Manuela M. Bergmann, Matthias B. Schulze, Marc J. Gunter, Anna Karakatsani, Daniel Ángel Rodríguez-Palacios, Vivian Viallon, Valeria Pala, Ruth C. Travis, Renée T. Fortner, Fulvio Ricceri, Rosario Tumino, Antonia Trichopoulou, Evelyn M. Monninkhof, Anne Tjønneland, Laure Dossus, Agnès Fournier, Aurelio Barricarte Gurrea, Anika Hüsing, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Cancer Research Foundation in Northern Sweden Ministerie van Volksgezondheid, Welzijn en Sport, VWS Deutsche Krebshilfe Cancer Research UK, CRUK: C8221/A19170, C570/A16491 Vetenskapsrådet, VR Ministerie van Volksgezondheid, Welzijn en Sport, VWS Ligue Contre le Cancer German Cancer Research Center, DKFZ Bundesministerium für Bildung und Forschung, BMBF Bundesministerium für Bildung und Forschung, BMBF Kræftens Bekæmpelse, DCS German Cancer Research Center, DKFZ Associazione Italiana per la Ricerca sul Cancro, AIRC National Research Council, NRC Mutuelle Générale de l'Education Nationale, MGEN Hellenic Health Foundation, HHF Institut National de la Santé et de la Recherche Médicale, Inserm Fondation Gustave Roussy European Commission, EC Centre International de Recherche sur le Cancer, IARC RD06/0020 German Cancer Research Center, DKFZ Deutsche Krebshilfe Cancerfonden World Cancer Research Fund, WCRF: ERC‐2009‐AdG 232997 PI13/01162, PI13/00061 NordForsk Medical Research Council, MRC: MR/M012190/1, The coordination of EPIC is financially supported by the European Commission (DG‐SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany), the Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro‐AIRC‐Italy and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), ERC‐2009‐AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway), Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC‐Murcia), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten, The Cancer Research Foundation of Northern Sweden (Sweden), Cancer Research UK (C570/A16491 and C8221/A19170), Medical Research Council (MR/M012190/1) (EPIC‐Oxford, and United Kingdom). The EPIC‐Norfolk study (doi: 10.22025/2019.10.105.00004) has received funding from the Medical Research Council (MR/N003284/1 and MC‐UU_12015/1) and Cancer Research UK (C864/A14136). We are grateful to all the participants who have been part of the project and to the many members of the study teams at the University of Cambridge who have enabled this research. For information on how to submit an application for gaining access to EPIC data and/or biospecimens, please follow the instructions at http://epic.iarc.fr/access/index.php .
Subjects: Cancer Research, primary prevention, Overweight, Body Mass Index, COLORECTAL-CANCER, Cohort Studies, 0302 clinical medicine, Endometrial cancer, Medicine, risk factors, endometrial cancer, 2. Zero hunger, Framingham Risk Score, Incidence, Incidence (epidemiology), Middle Aged, 3. Good health, Europe, Menopause, Oncology, 030220 oncology & carcinogenesis, Cohort, Female, NUTRITION, medicine.symptom, Cancer Epidemiology, Adult, Pes corporal, [SDV.CAN]Life Sciences [q-bio]/Cancer, Context (language use), BREAST, OVARIAN-CANCER, 03 medical and health sciences, Humans, Risk factor, Hormone therapy, Aged, Models, Statistical, business.industry, ORAL-CONTRACEPTIVE USE, Body weight, medicine.disease, Endometrial Neoplasms, Càncer d'endometri, business, Body mass index, Hormonoteràpia, Contraceptives, Oral, Demography
Abstract: Endometrial cancer (EC) incidence rates vary ~10‐fold worldwide, in part due to variation in EC risk factor profiles. Using an EC risk model previously developed in the European EPIC cohort, we evaluated the prevention potential of modified EC risk factor patterns and whether differences in EC incidence between a European population and low‐risk countries can be explained by differences in these patterns. Predicted EC incidence rates were estimated over 10 years of follow‐up for the cohort before and after modifying risk factor profiles. Risk factors considered were: body mass index (BMI, kg/m2), use of postmenopausal hormone therapy (HT) and oral contraceptives (OC) (potentially modifiable); and, parity, ages at first birth, menarche and menopause (environmentally conditioned, but not readily modifiable). Modeled alterations in BMI (to all ≤23 kg/m2) and HT use (to all non‐HT users) profiles resulted in a 30% reduction in predicted EC incidence rates; individually, longer duration of OC use (to all ≥10 years) resulted in a 42.5% reduction. Modeled changes in not readily modifiable exposures (i.e., those not contributing to prevention potential) resulted in ≤24.6% reduction in predicted EC incidence. Women in the lowest decile of a risk score based on the evaluated exposures had risk similar to a low risk countries; however, this was driven by relatively long use of OCs (median = 23 years). Our findings support avoidance of overweight BMI and of HT use as prevention strategies for EC in a European population; OC use must be considered in the context of benefits and risks., What's new? Endometrial cancer rates vary considerably around the world, with incidence rates higher in Europe and North America than in parts of Asia and Africa. Here, the authors investigated how much of the risk disparity arises from modifiable factors, and how much modifying these factors could reduce cancer incidence. The 10% of European women with lowest risk had similar incidence to women in low‐risk countries, they found. Their model predicted that in European women, maintaining BMI below 23 kg/m2 and avoiding postmenopausal hormone use could reduce risk by 30%. Long‐term use of oral contraceptives could reduce risk by 42.5%.
Published: 2020

29. A Body Shape Index (ABSI) achieves better mortality risk stratification than alternative indices of abdominal obesity: results from a large European cohort

Author: Christakoudi, S. Tsilidis, K.K. Muller, D.C. Freisling, H. Weiderpass, E. Overvad, K. Söderberg, S. Häggström, C. Pischon, T. Dahm, C.C. Zhang, J. Tjønneland, A. Halkjær, J. MacDonald, C. Boutron-Ruault, M.-C. Mancini, F.R. Kühn, T. Kaaks, R. Schulze, M.B. Trichopoulou, A. Karakatsani, A. Peppa, E. Masala, G. Pala, V. Panico, S. Tumino, R. Sacerdote, C. Quirós, J.R. Agudo, A. Sánchez, M.-J. Cirera, L. Barricarte-Gurrea, A. Amiano, P. Memarian, E. Sonestedt, E. Bueno-de-Mesquita, B. May, A.M. Khaw, K.-T. Wareham, N.J. Tong, T.Y.N. Huybrechts, I. Noh, H. Aglago, E.K. Ellingjord-Dale, M. Ward, H.A. Aune, D. Riboli, E.
Subjects: nutritional and metabolic diseases
Abstract: Abdominal and general adiposity are independently associated with mortality, but there is no consensus on how best to assess abdominal adiposity. We compared the ability of alternative waist indices to complement body mass index (BMI) when assessing all-cause mortality. We used data from 352,985 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) and Cox proportional hazards models adjusted for other risk factors. During a mean follow-up of 16.1 years, 38,178 participants died. Combining in one model BMI and a strongly correlated waist index altered the association patterns with mortality, to a predominantly negative association for BMI and a stronger positive association for the waist index, while combining BMI with the uncorrelated A Body Shape Index (ABSI) preserved the association patterns. Sex-specific cohort-wide quartiles of waist indices correlated with BMI could not separate high-risk from low-risk individuals within underweight (BMI < 18.5 kg/m2) or obese (BMI ≥ 30 kg/m2) categories, while the highest quartile of ABSI separated 18–39% of the individuals within each BMI category, which had 22–55% higher risk of death. In conclusion, only a waist index independent of BMI by design, such as ABSI, complements BMI and enables efficient risk stratification, which could facilitate personalisation of screening, treatment and monitoring. © 2020, The Author(s).
Published: 2020

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

Author: Elisabete Weiderpass, Kim Overvad, Giovanna Masala, Guy Fagherazzi, Rudolf Kaaks, Daniel Redondo-Sánchez, Sabina Rinaldi, Ulrica Ericson, Dagfinn Aune, Pilar Amiano, Therese Haugdahl Nøst, Antonia Trichopoulou, Rosario Tumino, Paula Jakszyn, Neil Murphy, Elio Riboli, Tilman Kühn, Francesca Mancini, Heinz Freisling, Bas Bueno-de-Mesquita, Marie-Christine Boutron-Ruault, Maria Santucci de Magistris, Inge Huybrechts, Marc J. Gunter, Carlotta Sacerdote, Nathalie Kliemann, Christina C. Dahm, Vivian Viallon, Vittorio Krogh, Lena Maria Nilsson, Isabel Drake, Anne M. May, Heiner Boeing, Matthias B. Schulze, Carlo La Vecchia, Anne Tjønneland, Anna Karakatsani, Aurelio Barricarte Gurrea, Konstantinos K. Tsilidis, María Dolores Chirlaque, José Ramón Quirós, Centre international de Recherche sur le Cancer (CIRC), Université de Paris-Saclay [Villejuif], Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Deutsche Krebshilfe Cancer Research UK, CRUK: C8221/A19170, 14136, C570/A16491 Ligue Contre le Cancer Bundesministerium für Bildung und Forschung, BMBF Bundesministerium für Bildung und Forschung, BMBF Institut National de la Santé et de la Recherche Médicale, Inserm Kræftens Bekæmpelse, DCS Research Councils UK, RCUK Health and Medical Research Fund, HMRF: FIS Zorginstituut Nederland, ZIN PI13/01162, PI13/00061 World Cancer Research Fund, WCRF: ERC‐2009‐AdG 232997 Associazione Italiana per la Ricerca sul Cancro, AIRC National Research Council, NRC Ecumenical Project for International Cooperation, EPIC Institut National de la Santé et de la Recherche Médicale, Inserm European Commission, EU Centre International de Recherche sur le Cancer, CIRC Norway Deutsches Krebsforschungszentrum, DKFZ: DKFZ World Cancer Research Fund, WCRF Cancerfonden NordForsk Medical Research Council, MRC: MR/M012190/1, 1000143, The authors would like to thank the EPIC study participants and staff for their valuable contribution to this research. The authors would also like to thank Mr Bertrand Hemon for his support in preparing the databases and Dr Joseph Rothwell for his support in creating the figures. The coordination of EPIC is financially supported by the European Commission (DGSANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM, France), German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF, Germany), the Hellenic Health Foundation (Greece), Associazione Italiana per la Ricerca sul Cancro‐AIRC‐Italy and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), ERC‐2009‐AdG 232997 and Nordforsk, Nordic Centre of Excellence Programme on Food, Nutrition and Health (Norway), Health Research Fund (FIS) of the Spanish Ministry of Health (FIS, PI13/00061 to Granada, PI13/01162 to EPIC‐Murcia), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra and the Catalan Institute of Oncology (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), Cancer Research UK (14136 to EPIC‐Norfolk, C570/A16491 and C8221/A19170 to EPIC‐Oxford), Medical Research Council (1000143 to EPIC‐Norfolk, MR/M012190/1 to EPIC‐Oxford, and United Kingdom).
Subjects: Oncology, Adult, Male, metabolic disorder, Cancer Research, medicine.medical_specialty, obesity, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Neoplasms, medicine, Humans, cancer, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, Prospective Studies, Risk factor, Càncer, Nutrició, Aged, Cancer, Nutrition, Sex Characteristics, business.industry, Incidence (epidemiology), Incidence, Hazard ratio, Metabolic disorder, Middle Aged, medicine.disease, Obesity, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Europe, Nutrition Assessment, 030220 oncology & carcinogenesis, Basal metabolic rate, basal metabolic rate, Female, Basal Metabolism, business
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 [HR 1-SD]: 2.46; 95% CI 1.20; 5.03) and distal colon cancer (HR 1-SD: 1.33; 95% CI 1.001; 1.77) among men and with proximal colon (HR 1-SD: 1.16; 95% CI 1.01; 1.35), pancreatic (HR 1-SD: 1.37; 95% CI 1.13; 1.66), thyroid (HR 1-SD: 1.65; 95% CI 1.33; 2.05), postmenopausal breast (HR 1-SD: 1.17; 95% CI 1.11; 1.22) and endometrial (HR 1-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.
Published: 2020

31. Lifestyle factors and risk of multimorbidity of cancer and cardiometabolic diseases: A multinational cohort study

Author: Manuela M. Bergmann, Elio Riboli, Christina C. Dahm, Marc J. Gunter, Christina Bamia, David C. Muller, Pauline Bazelle, Antonio Agudo, Isabelle Romieu, Heather Ward, Pietro Ferrari, Patrick Arveux, Anja Olsen, Tammy Y.N. Tong, Elin Thysell, Julie A. Schmidt, María José Sánchez, Adam S. Butterworth, Aurelio Barricarte Gurrea, Peter Nilsson, Pilar Amiano, Kim Overvad, Fulvio Ricceri, Rosario Tumino, Salvatore Panico, Michael J. Sweeting, Evelyn M. Monninkhof, Anne Tjønneland, Marina Kvaskoff, Vincenzo Bagnardi, Olov Rolandsson, Konstantinos K. Tsilidis, Mazda Jenab, H. Susan J. Picavet, Paolo Vineis, Tilman Kühn, Heinz Freisling, Gianluca Severi, John Danesh, Claudia Agnoli, Hannah Lennon, Marije F. Bakker, Vivian Viallon, Virginia Menéndez, Rudolf Kaaks, Nicholas J. Wareham, Heiner Boeing, Carmen Santiuste, Jonas Manjer, Elisabete Weiderpass, Domenico Palli, Ioanna Tzoulaki, Cristian Ricci, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), 2018-1-PL SHS-06-CIRC-1 LSHM_CT_2006_037197 HEALTH24 F2-2012-279233 PI13/00061, PI13/01162 2018-123 RD06/0020 G0800270, MR/ L003120/1 Kræftens Bekæmpelse, DCS German Cancer Research Center, DKFZ Centre International de Recherche sur le Cancer, IARC National Research Council, NRC Medical Research Council, MRC: MR/M012190/1 British Heart Foundation, BHF: 26 RG/08/014, RG13/ 13/30194, SP/09/002 Cancer Research UK, CRUK: C570/A16491, C8221/A19170 World Cancer Research Fund, WCRF European Commission, EC European Research Council, ERC: 268834 Bundesministerium für Bildung und Forschung, BMBF Cancerfonden Ministerie van Volksgezondheid, Welzijn en Sport, VWS Vetenskapsrådet, VR Ministère des Affaires Sociales et de la Santé: GR-IARC-2003-09-12-01 Direction Générale de la Compétitivité, de l’Industrie et des Services, DGCIS Associazione Italiana per la Ricerca sul Cancro, AIRC Deutsche Krebshilfe, This work was supported by the Direction Générale de la Santé (French Ministry of Health) (Grant GR-IARC-2003-09-12-01) and by the French National Cancer Institute (INCA_N°2018-123), and the Cancéropôle Ile-de-France (N°2018-1-PL SHS-06-CIRC-1). Funding for the InterAct project was provided by the EU FP6 programme (grant no. LSHM_CT_2006_037197). EPIC-CVD has been supported by the European Union Framework 7 (HEALTH24 F2-2012-279233), the European Research Council (268834), the UK Medical Research 25 Council (G0800270 and MR/ L003120/1), the British Heart Foundation (SP/09/002 and 26 RG/08/014 and RG13/ 13/30194), and the UK National Institute of Health Research. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC-Murcia), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), Cancer Research UK (14136 to EPIC-Norfolk, C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford) (UK). The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report., Butterworth, Adam [0000-0002-6915-9015], Danesh, John [0000-0003-1158-6791], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Cancer Research UK, Freisling, H, Viallon, V, Lennon, H, Bagnardi, V, Ricci, C, Butterworth, A, Sweeting, M, Muller, D, Romieu, I, Bazelle, P, Kvaskoff, M, Arveux, P, Severi, G, Bamia, C, Kuhn, T, Kaaks, R, Bergmann, M, Boeing, H, Tjonneland, A, Olsen, A, Overvad, K, Dahm, C, Menendez, V, Agudo, A, Sanchez, M, Amiano, P, Santiuste, C, Gurrea, A, Tong, T, Schmidt, J, Tzoulaki, I, Tsilidis, K, Ward, H, Palli, D, Agnoli, C, Tumino, R, Ricceri, F, Panico, S, Picavet, H, Bakker, M, Monninkhof, E, Nilsson, P, Manjer, J, Rolandsson, O, Thysell, E, Weiderpass, E, Jenab, M, Riboli, E, Vineis, P, Danesh, J, Wareham, N, Gunter, M, Ferrari, P, 29790514 - Ricci, Cristian, Overvad, Kim [0000-0001-6429-7921], Dahm, Christina C [0000-0003-0481-2893], and Tong, Tammy Y N [0000-0002-0284-8959]
Subjects: Male, lcsh:Medicine, Disease, Diabete, Body Mass Index, Cohort Studies, 0302 clinical medicine, Risk Factors, Neoplasms, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, Càncer, 11 Medical and Health Sciences, Cancer, 2. Zero hunger, Medicine(all), Incidence, Hazard ratio, Diabetes, General Medicine, Middle Aged, Cardiovascular disease, 3. Good health, Cardiovascular diseases, Cardiovascular Diseases, 030220 oncology & carcinogenesis, Obesitat, Female, Type 2, Cohort study, Research Article, Adult, Alcohol Drinking, Cancer and cardiometabolic multimorbidity, Healthy lifestyle, Obesity, Prevention, Diabetes Mellitus, Type 2, Humans, Proportional Hazards Models, Risk Reduction Behavior, Life Style, Multimorbidity, 03 medical and health sciences, Environmental health, General & Internal Medicine, medicine, Journal Article, Diabetes Mellitus, Cancer och onkologi, business.industry, Proportional hazards model, Malalties cardiovasculars, lcsh:R, medicine.disease, Cancer and Oncology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Body mass index
Abstract: Background Although lifestyle factors have been studied in relation to individual non-communicable diseases (NCDs), their association with development of a subsequent NCD, defined as multimorbidity, has been scarcely investigated. The aim of this study was to investigate associations between five lifestyle factors and incident multimorbidity of cancer and cardiometabolic diseases. Methods In this prospective cohort study, 291,778 participants (64% women) from seven European countries, mostly aged 43 to 58 years and free of cancer, cardiovascular disease (CVD), and type 2 diabetes (T2D) at recruitment, were included. Incident multimorbidity of cancer and cardiometabolic diseases was defined as developing subsequently two diseases including first cancer at any site, CVD, and T2D in an individual. Multi-state modelling based on Cox regression was used to compute hazard ratios (HR) and 95% confidence intervals (95% CI) of developing cancer, CVD, or T2D, and subsequent transitions to multimorbidity, in relation to body mass index (BMI), smoking status, alcohol intake, physical activity, adherence to the Mediterranean diet, and their combination as a healthy lifestyle index (HLI) score. Cumulative incidence functions (CIFs) were estimated to compute 10-year absolute risks for transitions from healthy to cancer at any site, CVD (both fatal and non-fatal), or T2D, and to subsequent multimorbidity after each of the three NCDs. Results During a median follow-up of 11 years, 1910 men and 1334 women developed multimorbidity of cancer and cardiometabolic diseases. A higher HLI, reflecting healthy lifestyles, was strongly inversely associated with multimorbidity, with hazard ratios per 3-unit increment of 0.75 (95% CI, 0.71 to 0.81), 0.84 (0.79 to 0.90), and 0.82 (0.77 to 0.88) after cancer, CVD, and T2D, respectively. After T2D, the 10-year absolute risks of multimorbidity were 40% and 25% for men and women, respectively, with unhealthy lifestyle, and 30% and 18% for men and women with healthy lifestyles. Conclusion Pre-diagnostic healthy lifestyle behaviours were strongly inversely associated with the risk of cancer and cardiometabolic diseases, and with the prognosis of these diseases by reducing risk of multimorbidity.
Published: 2020

32. Multiple miscarriages are associated with the risk of ovarian cancer: results from the European Prospective Investigation into Cancer and Nutrition.

Author: Marieke G M Braem, N Charlotte Onland-Moret, Leo J Schouten, Roy F P M Kruitwagen, Annekatrin Lukanova, Naomi E Allen, Petra A Wark, Anne Tjønneland, Louise Hansen, Christina Marie Braüner, Kim Overvad, Françoise Clavel-Chapelon, Nathalie Chabbert-Buffet, Birgit Teucher, Anna Floegel, Heiner Boeing, Antonia Trichopoulou, George Adarakis, Maria Plada, Sabina Rinaldi, Veronika Fedirko, Isabelle Romieu, Valeria Pala, Rocco Galasso, Carlotta Sacerdote, Domenico Palli, Rosario Tumino, H Bas Bueno-de-Mesquita, Inger Torhild Gram, Oxana Gavrilyuk, Eiliv Lund, Maria-José Sánchez, Catalina Bonet, Maria-Dolores Chirlaque, Nerea Larrañaga, Aurelio Barricarte Gurrea, Jose R Quirós, Annika Idahl, Nina Ohlson, Eva Lundin, Karin Jirström, Salma Butt, Konstantinos K Tsilidis, Kay-Tee Khaw, Nick Wareham, Elio Riboli, Rudolf Kaaks, and Petra H M Peeters
Subjects: Medicine, Science
Abstract: While the risk of ovarian cancer clearly reduces with each full-term pregnancy, the effect of incomplete pregnancies is unclear. We investigated whether incomplete pregnancies (miscarriages and induced abortions) are associated with risk of epithelial ovarian cancer. This observational study was carried out in female participants of the European Prospective Investigation into Cancer and Nutrition (EPIC). A total of 274,442 women were followed from 1992 until 2010. The baseline questionnaire elicited information on miscarriages and induced abortions, reproductive history, and lifestyle-related factors. During a median follow-up of 11.5 years, 1,035 women were diagnosed with incident epithelial ovarian cancer. Despite the lack of an overall association (ever vs. never), risk of ovarian cancer was higher among women with multiple incomplete pregnancies (HR(≥4vs.0): 1.74, 95% CI: 1.20-2.70; number of cases in this category: n = 23). This association was particularly evident for multiple miscarriages (HR(≥4vs.0): 1.99, 95% CI: 1.06-3.73; number of cases in this category: n = 10), with no significant association for multiple induced abortions (HR(≥4vs.0): 1.46, 95% CI: 0.68-3.14; number of cases in this category: n = 7). Our findings suggest that multiple miscarriages are associated with an increased risk of epithelial ovarian cancer, possibly through a shared cluster of etiological factors or a common underlying pathology. These findings should be interpreted with caution as this is the first study to show this association and given the small number of cases in the highest exposure categories.
Published: 2012
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33. Mediation analysis of the alcohol-postmenopausal breast cancer relationship by sex hormones in the EPIC cohort

Author: Assi, N, Rinaldi, S, Viallon, V, Dashti, SG, Dossus, L, Fournier, A, Cervenka, I, Kvaskoff, M, Turzanski-Fortner, R, Bergmann, M, Boeing, H, Panico, S, Ricceri, F, Palli, D, Tumino, R, Grioni, S, Sanchez Perez, MJ, Chirlaque, M-D, Bonet, C, Barricarte Gurrea, A, Amiano Etxezarreta, P, Merino, S, de Mesquita, HBB, van Gils, CH, Onland-Moret, C, Tjonneland, A, Overvad, K, Trichopoulou, A, Martimianaki, G, Karakatsani, A, Key, T, Christakoudi, S, Ellingjord-Dale, M, Tsilidis, K, Riboli, E, Kaaks, R, Gunter, MJ, Ferrari, P, Assi, N, Rinaldi, S, Viallon, V, Dashti, SG, Dossus, L, Fournier, A, Cervenka, I, Kvaskoff, M, Turzanski-Fortner, R, Bergmann, M, Boeing, H, Panico, S, Ricceri, F, Palli, D, Tumino, R, Grioni, S, Sanchez Perez, MJ, Chirlaque, M-D, Bonet, C, Barricarte Gurrea, A, Amiano Etxezarreta, P, Merino, S, de Mesquita, HBB, van Gils, CH, Onland-Moret, C, Tjonneland, A, Overvad, K, Trichopoulou, A, Martimianaki, G, Karakatsani, A, Key, T, Christakoudi, S, Ellingjord-Dale, M, Tsilidis, K, Riboli, E, Kaaks, R, Gunter, MJ, and Ferrari, P
Abstract: Alcohol consumption is associated with higher risk of breast cancer (BC); however, the biological mechanisms underlying this association are not fully elucidated, particularly the extent to which this relationship is mediated by sex hormone levels. Circulating concentrations of estradiol, testosterone, their free fractions and sex-hormone binding globulin (SHBG), were examined in 430 incident BC cases and 645 matched controls among alcohol-consuming postmenopausal women nested within the European Prospective Investigation into Cancer and Nutrition. Mediation analysis was applied to assess whether individual hormone levels mediated the relationship between alcohol intake and BC risk. An alcohol-related hormonal signature, obtained by partial least square (PLS) regression, was evaluated as a potential mediator. Total (TE), natural direct and natural indirect effects (NIE) were estimated. Alcohol intake was positively associated with overall BC risk and specifically with estrogen receptor-positive tumors with respectively TE = 1.17(95%CI: 1.01,1.35) and 1.36(1.08,1.70) for a 1-standard deviation (1-SD) increase of intake. There was no evidence of mediation by sex steroids or SHBG separately except for a weak indirect effect through free estradiol where NIE = 1.03(1.00,1.06). However, an alcohol-related hormonal signature negatively associated with SHBG and positively with estradiol and testosterone was associated with BC risk (odds ratio [OR] = 1.25 [1.07,1.47]) for a 1-SD higher PLS score, and had a statistically significant NIE accounting for a mediated proportion of 24%. There was limited evidence of mediation of the alcohol-BC association by individual sex hormones. However, a hormonal signature, reflecting lower levels of SHBG and higher levels of sex steroids, mediated a substantial proportion of the association.
Published: 2020

34. A Body Shape Index (ABSI) achieves better mortality risk stratification than alternative indices of abdominal obesity:results from a large European cohort

Author: Christakoudi, Sofia, Tsilidis, Konstantinos K., Muller, David C., Freisling, Heinz, Weiderpass, Elisabete, Overvad, Kim, Söderberg, Stefan, Häggström, Christel, Pischon, Tobias, Dahm, Christina C., Zhang, Jie, Tjønneland, Anne, Halkjær, Jytte, MacDonald, Conor, Boutron-Ruault, Marie Christine, Mancini, Francesca Romana, Kühn, Tilman, Kaaks, Rudolf, Schulze, Matthias B., Trichopoulou, Antonia, Karakatsani, Anna, Peppa, Eleni, Masala, Giovanna, Pala, Valeria, Panico, Salvatore, Tumino, Rosario, Sacerdote, Carlotta, Quirós, J. Ramón, Agudo, Antonio, Sánchez, Maria Jose, Cirera, Lluís, Barricarte-Gurrea, Aurelio, Amiano, Pilar, Memarian, Ensieh, Sonestedt, Emily, Bueno-de-Mesquita, Bas, May, Anne M., Khaw, Kay Tee, Wareham, Nicholas J., Tong, Tammy Y.N., Huybrechts, Inge, Noh, Hwayoung, Aglago, Elom K., Ellingjord-Dale, Merete, Ward, Heather A., Aune, Dagfinn, Riboli, Elio, Christakoudi, Sofia, Tsilidis, Konstantinos K., Muller, David C., Freisling, Heinz, Weiderpass, Elisabete, Overvad, Kim, Söderberg, Stefan, Häggström, Christel, Pischon, Tobias, Dahm, Christina C., Zhang, Jie, Tjønneland, Anne, Halkjær, Jytte, MacDonald, Conor, Boutron-Ruault, Marie Christine, Mancini, Francesca Romana, Kühn, Tilman, Kaaks, Rudolf, Schulze, Matthias B., Trichopoulou, Antonia, Karakatsani, Anna, Peppa, Eleni, Masala, Giovanna, Pala, Valeria, Panico, Salvatore, Tumino, Rosario, Sacerdote, Carlotta, Quirós, J. Ramón, Agudo, Antonio, Sánchez, Maria Jose, Cirera, Lluís, Barricarte-Gurrea, Aurelio, Amiano, Pilar, Memarian, Ensieh, Sonestedt, Emily, Bueno-de-Mesquita, Bas, May, Anne M., Khaw, Kay Tee, Wareham, Nicholas J., Tong, Tammy Y.N., Huybrechts, Inge, Noh, Hwayoung, Aglago, Elom K., Ellingjord-Dale, Merete, Ward, Heather A., Aune, Dagfinn, and Riboli, Elio
Abstract: Abdominal and general adiposity are independently associated with mortality, but there is no consensus on how best to assess abdominal adiposity. We compared the ability of alternative waist indices to complement body mass index (BMI) when assessing all-cause mortality. We used data from 352,985 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) and Cox proportional hazards models adjusted for other risk factors. During a mean follow-up of 16.1 years, 38,178 participants died. Combining in one model BMI and a strongly correlated waist index altered the association patterns with mortality, to a predominantly negative association for BMI and a stronger positive association for the waist index, while combining BMI with the uncorrelated A Body Shape Index (ABSI) preserved the association patterns. Sex-specific cohort-wide quartiles of waist indices correlated with BMI could not separate high-risk from low-risk individuals within underweight (BMI < 18.5 kg/m2) or obese (BMI ≥ 30 kg/m2) categories, while the highest quartile of ABSI separated 18–39% of the individuals within each BMI category, which had 22–55% higher risk of death. In conclusion, only a waist index independent of BMI by design, such as ABSI, complements BMI and enables efficient risk stratification, which could facilitate personalisation of screening, treatment and monitoring.
Published: 2020

35. Mediation analysis of the alcohol-postmenopausal breast cancer relationship by sex hormones in the EPIC cohort

Author: Assi, Nada, Rinaldi, Sabina, Viallon, Vivian, Dashti, S. Ghazaleh, Dossus, Laure, Fournier, Agnes, Cervenka, Iris, Kvaskoff, Marina, Turzanski-Fortner, Renee, Bergmann, Manuela, Boeing, Heiner, Panico, Salvatore, Ricceri, Fulvio, Palli, Domenico, Tumino, Rosario, Grioni, Sara, Sanchez Perez, Maria Jose, Chirlaque, Maria-Dolores, Bonet, Catalina, Barricarte Gurrea, Aurelio, Amiano Etxezarreta, Pilar, Merino, Susana, de Mesquita, H. Bas Bueno, van Gils, Carla H., Onland-Moret, Charlotte, Tjonneland, Anne, Overvad, Kim, Trichopoulou, Antonia, Martimianaki, Georgia, Karakatsani, Anna, Key, Tim, Christakoudi, Sofia, Ellingjord-Dale, Merete, Tsilidis, Kostas, Riboli, Elio, Kaaks, Rudolf, Gunter, Marc J., Ferrari, Pietro, Assi, Nada, Rinaldi, Sabina, Viallon, Vivian, Dashti, S. Ghazaleh, Dossus, Laure, Fournier, Agnes, Cervenka, Iris, Kvaskoff, Marina, Turzanski-Fortner, Renee, Bergmann, Manuela, Boeing, Heiner, Panico, Salvatore, Ricceri, Fulvio, Palli, Domenico, Tumino, Rosario, Grioni, Sara, Sanchez Perez, Maria Jose, Chirlaque, Maria-Dolores, Bonet, Catalina, Barricarte Gurrea, Aurelio, Amiano Etxezarreta, Pilar, Merino, Susana, de Mesquita, H. Bas Bueno, van Gils, Carla H., Onland-Moret, Charlotte, Tjonneland, Anne, Overvad, Kim, Trichopoulou, Antonia, Martimianaki, Georgia, Karakatsani, Anna, Key, Tim, Christakoudi, Sofia, Ellingjord-Dale, Merete, Tsilidis, Kostas, Riboli, Elio, Kaaks, Rudolf, Gunter, Marc J., and Ferrari, Pietro
Abstract: Alcohol consumption is associated with higher risk of breast cancer (BC); however, the biological mechanisms underlying this association are not fully elucidated, particularly the extent to which this relationship is mediated by sex hormone levels. Circulating concentrations of estradiol, testosterone, their free fractions and sex-hormone binding globulin (SHBG), were examined in 430 incident BC cases and 645 matched controls among alcohol-consuming postmenopausal women nested within the European Prospective Investigation into Cancer and Nutrition. Mediation analysis was applied to assess whether individual hormone levels mediated the relationship between alcohol intake and BC risk. An alcohol-related hormonal signature, obtained by partial least square (PLS) regression, was evaluated as a potential mediator. Total (TE), natural direct and natural indirect effects (NIE) were estimated. Alcohol intake was positively associated with overall BC risk and specifically with estrogen receptor-positive tumors with respectively TE = 1.17(95%CI: 1.01,1.35) and 1.36(1.08,1.70) for a 1-standard deviation (1-SD) increase of intake. There was no evidence of mediation by sex steroids or SHBG separately except for a weak indirect effect through free estradiol where NIE = 1.03(1.00,1.06). However, an alcohol-related hormonal signature negatively associated with SHBG and positively with estradiol and testosterone was associated with BC risk (odds ratio [OR] = 1.25 [1.07,1.47]) for a 1-SD higher PLS score, and had a statistically significant NIE accounting for a mediated proportion of 24%. There was limited evidence of mediation of the alcohol-BC association by individual sex hormones. However, a hormonal signature, reflecting lower levels of SHBG and higher levels of sex steroids, mediated a substantial proportion of the association.
Published: 2020

36. A Body Shape Index (ABSI) achieves better mortality risk stratification than alternative indices of abdominal obesity: results from a large European cohort

Author: Utrecht Palliatie Centrum, MS MDL 1, Epidemiology & Health Economics, Cancer, JC onderzoeksprogramma Kanker, Christakoudi, Sofia, Tsilidis, Konstantinos K, Muller, David C, Freisling, Heinz, Weiderpass, Elisabete, Overvad, Kim, Söderberg, Stefan, Häggström, Christel, Pischon, Tobias, Dahm, Christina C, Zhang, Jie, Tjønneland, Anne, Halkjær, Jytte, MacDonald, Conor, Boutron-Ruault, Marie-Christine, Mancini, Francesca Romana, Kühn, Tilman, Kaaks, Rudolf, Schulze, Matthias B, Trichopoulou, Antonia, Karakatsani, Anna, Peppa, Eleni, Masala, Giovanna, Pala, Valeria, Panico, Salvatore, Tumino, Rosario, Sacerdote, Carlotta, Quirós, J Ramón, Agudo, Antonio, Sánchez, Maria-Jose, Cirera, Lluís, Barricarte-Gurrea, Aurelio, Amiano, Pilar, Memarian, Ensieh, Sonestedt, Emily, Bueno-de-Mesquita, Bas, May, Anne M, Khaw, Kay-Tee, Wareham, Nicholas J, Tong, Tammy Y N, Huybrechts, Inge, Noh, Hwayoung, Aglago, Elom K, Ellingjord-Dale, Merete, Ward, Heather A, Aune, Dagfinn, Riboli, Elio, Utrecht Palliatie Centrum, MS MDL 1, Epidemiology & Health Economics, Cancer, JC onderzoeksprogramma Kanker, Christakoudi, Sofia, Tsilidis, Konstantinos K, Muller, David C, Freisling, Heinz, Weiderpass, Elisabete, Overvad, Kim, Söderberg, Stefan, Häggström, Christel, Pischon, Tobias, Dahm, Christina C, Zhang, Jie, Tjønneland, Anne, Halkjær, Jytte, MacDonald, Conor, Boutron-Ruault, Marie-Christine, Mancini, Francesca Romana, Kühn, Tilman, Kaaks, Rudolf, Schulze, Matthias B, Trichopoulou, Antonia, Karakatsani, Anna, Peppa, Eleni, Masala, Giovanna, Pala, Valeria, Panico, Salvatore, Tumino, Rosario, Sacerdote, Carlotta, Quirós, J Ramón, Agudo, Antonio, Sánchez, Maria-Jose, Cirera, Lluís, Barricarte-Gurrea, Aurelio, Amiano, Pilar, Memarian, Ensieh, Sonestedt, Emily, Bueno-de-Mesquita, Bas, May, Anne M, Khaw, Kay-Tee, Wareham, Nicholas J, Tong, Tammy Y N, Huybrechts, Inge, Noh, Hwayoung, Aglago, Elom K, Ellingjord-Dale, Merete, Ward, Heather A, Aune, Dagfinn, and Riboli, Elio
Published: 2020

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

Author: MS MDL 1, Epidemiology & Health Economics, Cancer, JC onderzoeksprogramma Kanker, Kliemann, Nathalie, Murphy, Neil, Viallon, Vivian, Freisling, Heinz, Tsilidis, Konstantinos K, Rinaldi, Sabina, Mancini, Francesca Romana, Fagherazzi, Guy, Boutron-Ruault, Marie-Christine, Boeing, Heiner, Schulze, Matthias B, Masala, Giovanna, Krogh, Vittorio, Sacerdote, Carlotta, Santucci de Magistris, Maria, Bueno-de-Mesquita, Bas, Weiderpass, Elisabete, Kühn, Tilman, Kaaks, Rudolf, Jakszyn, Paula, Redondo-Sánchez, Daniel, Amiano, Pilar, Chirlaque, Maria-Dolores, Barricarte Gurrea, Aurelio, Ericson, Ulrica, Drake, Isabel, Nøst, Therese Haugdahl, Aune, Dagfinn, May, Anne M, Tjønneland, Anne, Dahm, Christina Catherine, Overvad, Kim, Tumino, Rosario, Ramón Quirós, Jose, Trichopoulou, Antonia, Karakatsani, Anna, La Vecchia, Carlo, Nilsson, Lena Maria, Riboli, Elio, Huybrechts, Inge, Gunter, Marc J, MS MDL 1, Epidemiology & Health Economics, Cancer, JC onderzoeksprogramma Kanker, Kliemann, Nathalie, Murphy, Neil, Viallon, Vivian, Freisling, Heinz, Tsilidis, Konstantinos K, Rinaldi, Sabina, Mancini, Francesca Romana, Fagherazzi, Guy, Boutron-Ruault, Marie-Christine, Boeing, Heiner, Schulze, Matthias B, Masala, Giovanna, Krogh, Vittorio, Sacerdote, Carlotta, Santucci de Magistris, Maria, Bueno-de-Mesquita, Bas, Weiderpass, Elisabete, Kühn, Tilman, Kaaks, Rudolf, Jakszyn, Paula, Redondo-Sánchez, Daniel, Amiano, Pilar, Chirlaque, Maria-Dolores, Barricarte Gurrea, Aurelio, Ericson, Ulrica, Drake, Isabel, Nøst, Therese Haugdahl, Aune, Dagfinn, May, Anne M, Tjønneland, Anne, Dahm, Christina Catherine, Overvad, Kim, Tumino, Rosario, Ramón Quirós, Jose, Trichopoulou, Antonia, Karakatsani, Anna, La Vecchia, Carlo, Nilsson, Lena Maria, Riboli, Elio, Huybrechts, Inge, and Gunter, Marc J
Published: 2020

38. Prospective analysis of circulating metabolites and endometrial cancer risk

Author: Alicia K Heath, Eirini Kouloura, Pilar Amiano, Joseph A. Rothwell, Marta Crous-Bou, Konstantinos K. Tsilidis, Melissa A. Merritt, Julie A. Schmidt, Lucie Lécuyer, María José Sánchez, Rosario Tumino, Domenico Palli, Hector C. Keun, Marc J. Gunter, Roel Vermeulen, Matthias B. Schulze, Inger T. Gram, Laure Dossus, Amalia Mattiello, Aurelio Barricarte Gurrea, Sandra Colorado-Yohar, Therese Haugdahl Nøst, Ruth C. Travis, Gianluca Severi, Carlotta Sacerdote, Claudia Agnoli, Naomi E. Allen, Elisabete Weiderpass, Alexandros P. Siskos, Carine Biessy, Vivian Viallon, Renée T. Fortner, Rudolf Kaaks, Niki Dimou, Sofia Christakoudi, Sabina Rinaldi, Sub Inorganic Chemistry and Catalysis, IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, International Agency for Cancer Research (IACR), Imperial College London, European Food Safety Authority (EFSA), University of Hawai'i [Honolulu] (UH), Nuffield Department of Population Health [Oxford], University of Oxford [Oxford], German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), University Hospital of North Norway [Tromsø] (UNN), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, University of Potsdam, Harvard T.H. Chan School of Public Health, University of Granada [Granada], CIBER de Epidemiología y Salud Pública (CIBERESP), Institute for Cancer Research, Prevention and Clinical Network (ISPRO), IRCCS Istituto Nazionale dei Tumori [Milano], Provincial Health Authority (ASP 7) [Ragusa, Italy], University Hospital Città della Salute e della Scienza di Torino, University of Naples Federico II, Utrecht University [Utrecht], Kræftens Bekæmpelse, DCS, Deutsches Krebsforschungszentrum, DKFZ, Centre International de Recherche sur le Cancer, CIRC, Academy of Pharmaceutical Sciences, APS, National Research Council, NRC, Imperial Experimental Cancer Medicine Centre, ECMC, University of Maryland School of Public Health, SPH, Medical Research Council, MRC: MR/M012190/1, Cancer Research UK, CRUK: C19335/A21351, C8221/ A29017, World Cancer Research Fund, WCRF, Institut National de la Santé et de la Recherche Médicale, Inserm, Bundesministerium für Bildung und Forschung, BMBF, Cancerfonden, Ministerie van Volksgezondheid, Welzijn en Sport, VWS, Ligue Contre le Cancer, Vetenskapsrådet, VR, Instituto de Salud Carlos III, ISCIII, Associazione Italiana per la Ricerca sul Cancro, AIRC, Deutsche Krebshilfe, Institut Gustave-Roussy, Mutuelle Générale de l'Education Nationale, MGEN, NIHR Imperial Biomedical Research Centre, BRC, This work was supported by Cancer Research UK (CRUK) (grant number C19335/A21351, to MJG and HK).The metabolomics infrastructure in the Division of Cancer, Imperial College London is supported by the Imperial College Experimental Cancer Medicine Centre, the Imperial College Cancer Research UK Centre and the NIHR Imperial Biomedical Research Centre (APS & HK). The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by: Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle G?n?rale de l'Education Nationale, Institut National de la Sant? et de la Recherche M?dicale (INSERM) (France), German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition PotsdamRehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany), Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands), Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), Regional Governments of Andaluc?a, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO (Spain), Swedish Cancer Society, Swedish Research Council and County Councils of Sk?ne and V?sterbotten (Sweden), Cancer Research UK (14136 to EPIC-Norfolk, C8221/A29017 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/M012190/1 to EPIC-Oxford). (United Kingdom)., The metabolomics infrastructure in the Division of Cancer, Imperial College London is supported by the Imperial College Experimental Cancer Medicine Centre , the Imperial College Cancer Research UK Centre and the NIHR Imperial Biomedical Research Centre (APS & HK). The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics , School of Public Health , Imperial College London which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC) . The national cohorts are supported by: Danish Cancer Society (Denmark), Ligue Contre le Cancer , Institut Gustave Roussy , Mutuelle Générale de l'Education Nationale , Institut National de la Santé et de la Recherche Médicale (INSERM) (France), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds , Dutch Prevention Funds , Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF) , Statistics Netherlands (The Netherlands), Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII) , Regional Governments of Andalucía, Asturias , Basque Country, Murcia and Navarra , and the Catalan Institute of Oncology - ICO (Spain), Swedish Cancer Society , Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden), Cancer Research UK ( 14136 to EPIC-Norfolk, C8221/ A29017 to EPIC-Oxford), Medical Research Council ( 1000143 to EPIC-Norfolk, This work was supported by Cancer Research UK (CRUK) (grant number C19335/A21351 , to MJG and HK)., University of Oxford, University of Naples Federico II = Università degli studi di Napoli Federico II, Azienda Ospedalerio - Universitaria Città della Salute e della Scienza di Torino = University Hospital Città della Salute e della Scienza di Torino, Universidad de Granada = University of Granada (UGR), University of Potsdam = Universität Potsdam, HAL UVSQ, Équipe, Cancer Research UK, and Imperial College Healthcare NHS Trust- BRC Funding
Subjects: 0301 basic medicine, Trastorns del metabolisme, [SDV]Life Sciences [q-bio], BMI, body mass index, NIST, National Institute of Standards and Technology, Body Mass Index, Serine, 0302 clinical medicine, Endometrial cancer, Risk Factors, WC, waist circumference, LC-MS/MS, liquid chromatography-tandem mass spectrometry, Prospective Studies, 2. Zero hunger, SPHINGOMYELIN, Endometrial Neoplasms/blood, Sphingomyelins/blood, Obstetrics & Gynecology, Obstetrics and Gynecology, C0, free carnitine, Middle Aged, Lipids, MHT, menopausal hormone therapy, AMINO-ACID, Sphingomyelins, 3. Good health, European Prospective Investigation into Cancer and Nutrition, [SDV] Life Sciences [q-bio], Disorders of metabolism, Oncology, 030220 oncology & carcinogenesis, Obesitat, Amino acids, Tumor/blood, NUTRITION, Female, ULOQ, upper limit of quantification, Life Sciences & Biomedicine, medicine.medical_specialty, Carnitine/blood, medicine.drug_class, MODELS, Glycine, LLOQ, lower limit of quantification, Glycine/blood, Malignancy, Article, 03 medical and health sciences, Carnitine, Internal medicine, Biomarkers, Tumor, medicine, Humans, Metabolomics, 1112 Oncology and Carcinogenesis, Serine/blood, Oncology & Carcinogenesis, Obesity, Aged, SRM, standard reference material, Science & Technology, LOD, limit of detection, SM, sphingomyelin, EPIC, European Prospective Investigation into Cancer and Nutrition, business.industry, IARC, International Agency for Research on Cancer, PROFILES, Odds ratio, medicine.disease, SYNTHASES, Sphingolipid, Endometrial Neoplasms, BODY-MASS INDEX, CI, confidence interval, OR, odds ratio, 030104 developmental biology, Endocrinology, Càncer d'endometri, Estrogen, Biomarkers, Tumor/blood, Case-Control Studies, 1114 Paediatrics and Reproductive Medicine, SD, standard deviation, business, CVs, coefficients of variation, Body mass index, Biomarkers
Abstract: This work was supported by Cancer Research UK (CRUK) (grant number C19335/A21351, to MJG and HK) . The metabolomics infrastructure in the Division of Cancer, Imperial College London is supported by the Imperial College Experimental Can-cer Medicine Centre, the This work was supported by Cancer Research UK (CRUK) (grant number C19335/A21351, to MJG and HK) . The metabolomics infrastructure in the Division of Cancer, Imperial College London is supported by the Imperial College Experimental Can-cer Medicine Centre, the Imperial College Cancer Research UK Centre and the NIHR Imperial Biomedical Research Centre (APS & HK) . The co-ordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the NIHR Im-perial Biomedical Research Centre (BRC) . The national cohorts are sup-ported by: Danish Cancer Society (Denmark) ; Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM) (France) ; German Cancer Aid, German Cancer Research Center (DKFZ) , German Institute of Human Nutrition PotsdamRehbruecke (DIfE) , Federal Ministry of Education and Research (BMBF) (Germany) ; Associazione Italiana per la Ricerca sul CancroAIRCItaly, Compagnia di SanPaolo and National Research Council (Italy) ; Dutch Ministry of Public Health, Welfare and Sports (VWS) , Netherlands Can-cer Registry (NKR) , LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland) , World Cancer Research Fund (WCRF) , Statistics Netherlands (The Netherlands) ; Health Research Fund (FIS) -Instituto de Salud Carlos III (ISCIII) , Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology-ICO (Spain) ; Swedish Cancer Society, Swedish Research Council and County Councils of Skkne and Vasterbotten (Sweden) ; Cancer Research UK (14136 to EPICNorfolk; C8221/A29017 to EPICOxford) , Medical Research Council (1000143 to EPICNorfolk; MR/M012190/1 to EPICOxford) . (United Kingdom) ., Background. Endometrial cancer is strongly associated with obesity and dysregulation of metabolic factors such as estrogen and insulin signaling are causal risk factors for this malignancy. To identify additional novel metabolic pathways associated with endometrial cancer we performed metabolomic analyses on pre-diagnostic plasma samples from853 case-control pairs fromthe European Prospective Investigation into Cancer and Nutrition (EPIC). Methods. A total of 129metabolites (acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexoses, and sphingolipids) were measured by liquid chromatography-mass spectrometry. Conditional logistic regression estimated the associations of metabolites with endometrial cancer risk. An analysis focusing on clusters of metabolites using the bootstrap lasso method was also employed. Results. After adjustment for body mass index, sphingomyelin [SM] C18:0was positively (OR1SD: 1.18,95%CI: 1.05–1.33), and glycine, serine, and free carnitine (C0) were inversely (OR1SD: 0.89, 95% CI: 0.80–0.99; OR1SD: 0.89, 95% CI: 0.79–1.00 and OR1SD: 0.91, 95% CI: 0.81–1.00, respectively) associated with endometrial cancer risk. Serine, C0 and two sphingomyelins were selected by the lasso method in >90% of the bootstrap samples. The ratio of esterified to free carnitine (OR1SD: 1.14, 95% CI: 1.02–1.28) and that of short chain to free acylcarnitines (OR1SD: 1.12, 95% CI: 1.00–1.25) were positively associated with endometrial cancer risk. Further adjustment for C-peptide or other endometrial cancer risk factors only minimally altered the results. Conclusion. These findings suggest that variation in levels of glycine, serine, SMC18:0 and free carnitine may represent specific pathways linked to endometrial cancer development. If causal, these pathways may offer novel targets for endometrial cancer prevention., Cancer Research UK C19335/A21351, Imperial College Experimental Cancer Medicine Centre Imperial College Cancer Research UK Centre, NIHR Imperial Biomedical Research Centre, World Health Organization, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Danish Cancer Society, Ligue Contre le Cancer (France) Institut Gustave Roussy (France) Mutuelle Generale de l'Education Nationale (France), Institut National de la Sante et de la Recherche Medicale (Inserm), Deutsche Krebshilfe, German Cancer Research Center (DKFZ) (Germany) German Institute of Human Nutrition PotsdamRehbruecke (DIfE) (Germany), Federal Ministry of Education & Research (BMBF), Fondazione AIRC per la ricerca sul cancro Compagnia di San Paolo Consiglio Nazionale delle Ricerche (CNR), Netherlands Government Netherlands Government, World Cancer Research Fund International (WCRF), Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII) (Spain), Junta de Andalucia, Regional Government of Asturias (Spain), Regional Government of Basque Country (Spain), Regional Government of Murcia (Spain), Regional Government of Navarra (Spain), Catalan Institute of Oncology-ICO (Spain), Swedish Cancer Society, Swedish Research Council, County Council of Skkne (Sweden), County Council of Vasterbotten (Sweden), Cancer Research UK 14136 C8221/A29017, UK Research & Innovation (UKRI), Medical Research Council UK (MRC) 1000143 MR/M012190/1
Published: 2021

39. 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: Kim Overvad, Rosario Tumino, Isabel Drake, Pietro Ferrari, Anna Karakatsani, Fulvio Ricceri, Antonio Agudo, Piet A. van den Brandt, Milan Geybels, María José Sánchez, Paolo Vineis, Tilman Kühn, Timothy J. Key, Aurelio Barricarte Gurrea, Chirag J. Patel, Georgia Martimianaki, Elio Riboli, Bas Bueno-de-Mesquita, David S. Lopez, Nerea Larrañaga, Marc J. Gunter, David C. Muller, Vittorio Krogh, Kay-Tee Khaw, José Ramón Quirós, Domenico Palli, Antonia Trichopoulou, Ioanna Tzoulaki, Nikos Papadimitriou, Renée T. Fortner, Pär Stattin, Elisabete Weiderpass, Carmen Santiuste, Ingegerd Johansson, Konstantinos K. Tsilidis, Anne Tjønneland, Heiner Boeing, Dorthe Furstrand Lauritzen, Anders Bjartell, Aurora Perez-Cornago, Elin Thysell, World Cancer Research Fund International, Epidemiologie, RS: GROW - R1 - Prevention, RS: CAPHRI - R5 - Optimising Patient Care, Tsilidis, Konstantinos K [0000-0002-8452-8472], Apollo - University of Cambridge Repository, and Tsilidis, Konstantinos K. [0000-0002-8452-8472]
Subjects: Male, Oncology, Epidemiology, Medicine (miscellaneous), Cohort Studies, Prostate cancer, 0302 clinical medicine, Risk Factors, Medicine, Prospective Studies, 030212 general & internal medicine, INDEX, Netherlands, Nutrition and Dietetics, Hazard ratio, Original Contribution, European Prospective Investigation into Cancer and Nutrition, Europe, Näringslära, 030220 oncology & carcinogenesis, Cohort, Cohort study, Life Sciences & Biomedicine, medicine.medical_specialty, Diet, Nutrition, QUESTIONNAIRE, OVARIAN-CANCER, CALCIUM, DIET, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Internal medicine, CARBOHYDRATE, Humans, Science & Technology, Nutrition & Dietetics, business.industry, SCALE PROSPECTIVE COHORT, Prostatic Neoplasms, Nutrients, medicine.disease, Confidence interval, PRODUCTS, PHYSICAL-ACTIVITY, 1111 Nutrition and Dietetics, business, Body mass index, Genome-Wide Association Study
Abstract: Funder: Centre International de Recherche sur le Cancer; doi: http://dx.doi.org/10.13039/100008700, 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.
Published: 2019

40. Association of circulating Vitamin D with colorectal cancer depends on Vitamin D-binding protein isoforms: A pooled, nested, case-control study

Author: W. Dana Flanders, Tilman Kühn, Anne Tjønneland, Kana Wu, Roberd M. Bostick, Yahya Mahamat-Saleh, Marjorie L. McCullough, Aurelio Barricarte Gurrea, Konstantinos K. Tsilidis, Antonia Trichopoulou, Johan Hultdin, Bas Bueno-de-Mesquita, Mingyang Song, Elisabete Weiderpass, Edward Giovannucci, David C. Gibbs, Magritt Brustad, Marc J. Gunter, Veronika Fedirko, Mazda Jenab, Aurora Perez-Cornago, Caroline Y. Um, Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), and Institut Gustave Roussy (IGR)
Subjects: Vitamin, 25-HYDROXYVITAMIN D, D SUPPLEMENTATION, Cancer Research, medicine.medical_specialty, Vitamin D-binding protein, [SDV]Life Sciences [q-bio], Lower risk, Gastroenterology, CALCIUM, Article, vitamin D deficiency, SERUM, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, D-RECEPTOR, GENETIC-VARIANTS, GC-GLOBULIN, Internal medicine, Vitamin D and neurology, Medicine, GENOME-WIDE ASSOCIATION, 030304 developmental biology, RISK, 0303 health sciences, Cancer och onkologi, Science & Technology, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, business.industry, Odds ratio, medicine.disease, PREVENTION, Confidence interval, 3. Good health, Oncology, chemistry, 030220 oncology & carcinogenesis, Cancer and Oncology, Nested case-control study, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business, Life Sciences & Biomedicine
Abstract: Background Higher circulating 25-hydroxyvitamin-D [25(OH)D] concentrations are consistently inversely associated with colorectal cancer (CRC) risk in observational studies. However, it is unknown whether this association depends on the functional GC-rs4588*A (Thr436Lys) variant encoding the vitamin D–binding protein-2 (DBP2) isoform, which may affect vitamin D status and bioavailability. Methods We analyzed data from 1710 incident CRC cases and 1649 incidence-density–matched controls nested within three prospective cohorts of mostly Caucasians. Study-specific incidence rate ratios (RRs) for associations of prediagnostic, season-standardized 25(OH)D concentrations according to DBP2 isoform with CRC were estimated using multivariable unconditional logistic regression and were pooled using fixed-effects models. All statistical significance tests were two-sided. Results The odds of having 25(OH)D concentrations less than 50 nmol/L (considered insufficient by the Institute of Medicine) were 43% higher for each DBP2-encoding variant (rs4588*A) inherited (per DBP2 odds ratio [OR] = 1.43, 95% confidence interval [CI] = 1.27 to 1.62, Ptrend = 1.2 × 10−8). The association of 25(OH)D concentrations with CRC risk differed by DBP2: 25(OH)D concentrations considered sufficient (≥ 50 nmol/L), relative to deficient ( Conclusions Our results suggest that the 25(OH)D-CRC association may differ by DBP isoform, and those with a DBP2-encoding genotype linked to vitamin D insufficiency may particularly benefit from adequate 25(OH)D for CRC prevention.
Published: 2019

41. Mediation analysis of the alcohol‐postmenopausal breast cancer relationship by sex hormones in the EPIC Cohort

Author: Anne Tjønneland, Georgia Martimianaki, Laure Dossus, Vivian Viallon, Iris Cervenka, H. Bas Bueno de Mesquita, Rosario Tumino, Marina Kvaskoff, Merete Ellingjord-Dale, Susana Merino, Anna Karakatsani, Kim Overvad, Manuela M. Bergmann, Sabina Rinaldi, Kostas Tsilidis, María José Sánchez Pérez, Pilar Amiano Etxezarreta, Rudolf Kaaks, Elio Riboli, Sara Grioni, Catalina Bonet, Agnès Fournier, Domenico Palli, Maria Dolores Chirlaque, Nada Assi, Sofia Christakoudi, Antonia Trichopoulou, Fulvio Ricceri, Marc J. Gunter, S. Ghazaleh Dashti, Renée Turzanski-Fortner, Charlotte Onland-Moret, Carla H. van Gils, Heiner Boeing, Salvatore Panico, Pietro Ferrari, Timothy J. Key, Aurelio Barricarte Gurrea, and Commission of the European Communities
Subjects: Cancer Research, 0302 clinical medicine, Sex hormone-binding globulin, Breast cancer, Sex Hormone-Binding Globulin, hormonal signature, Testosterone, Sex hormones, Prospective Studies, Hormones sexuals, biology, Estradiol, alcohol, Incidence, Middle Aged, European Prospective Investigation into Cancer and Nutrition, Postmenopause, Oncology, Drinking of alcoholic beverages, 030220 oncology & carcinogenesis, breast cancer, EPIC, mediation analysis, sex steroids, Aged, Alcohol Drinking, Breast Neoplasms, Case-Control Studies, Female, Humans, Consum d'alcohol, medicine.medical_specialty, medicine.drug_class, Article, Càncer de mama, 03 medical and health sciences, Internal medicine, medicine, Journal Article, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, business.industry, Case-control study, Odds ratio, medicine.disease, Endocrinology, Estrogen, biology.protein, business, Hormone
Abstract: Alcohol consumption is associated with higher risk of breast cancer (BC); however, the biological mechanisms underlying this association are not fully elucidated, particularly the extent to which this relationship is mediated by sex hormone levels. Circulating concentrations of estradiol, testosterone, their free fractions and sex-hormone binding globulin (SHBG), were examined in 430 incident BC cases and 645 matched controls among alcohol-consuming postmenopausal women nested within the European Prospective Investigation into Cancer and Nutrition. Mediation analysis was applied to assess whether individual hormone levels mediated the relationship between alcohol intake and BC risk. An alcohol-related hormonal signature, obtained by Partial Least Square (PLS) regression, was evaluated as a potential mediator. Total (TE), natural direct (NDE) and natural indirect effects (NIE) were estimated. Alcohol intake was positively associated with overall BC risk and specifically with estrogen receptor positive tumours with respectively TE=1.17(95%CI: 1.01,1.35) and 1.36(1.08,1.70) for a 1-SD deviation increase of intake. There was no evidence of mediation by sex steroids or SHBG separately except for a weak indirect effect through free estradiol where NIE=1.03(1.00,1.06). However, an alcohol-related hormonal signature negatively associated with SHBG and positively with estradiol and testosterone, was associated with BC risk (OR=1.25 (1.07,1.47)) for a 1-SD higher PLS score, and had a statistically significant NIE accounting for a mediated proportion of 24%. There was limited evidence of mediation of the alcohol-BC association by individual sex hormones. However, a hormonal signature, reflecting lower levels of SHBG and higher levels of sex steroids, mediated a substantial proportion of the association. This article is protected by copyright. All rights reserved.
Published: 2019

42. Comparison of prognostic models to predict the occurrence of colorectal cancer in asymptomatic individuals : a systematic literature review and external validation in the EPIC and UK Biobank prospective cohort studies

Author: Smith, Todd, Muller, David C., Moons, Karel G. M., Cross, Amanda J., Johansson, Mattias, Ferrari, Pietro, Fagherazzi, Guy, Peeters, Petra H. M., Severi, Gianluca, Hüsing, Anika, Kaaks, Rudolf, Tjonneland, Anne, Olsen, Anja, Overvad, Kim, Bonet, Catalina, Rodriguez-Barranco, Miguel, Huerta, Jose Maria, Barricarte Gurrea, Aurelio, Bradbury, Kathryn E., Trichopoulou, Antonia, Bamia, Christina, Orfanos, Philippos, Palli, Domenico, Pala, Valeria, Vineis, Paolo, Bueno-de-Mesquita, Bas, Ohlsson, Bodil, Harlid, Sophia, van Guelpen, Bethany, Skeie, Guri, Weiderpass, Elisabete, Jenab, Mazda, Murphy, Neil, Riboli, Elio, Gunter, Marc J., Aleksandrova, Krasimira Jekova, Tzoulaki, Ioanna, Smith, Todd, Muller, David C., Moons, Karel G. M., Cross, Amanda J., Johansson, Mattias, Ferrari, Pietro, Fagherazzi, Guy, Peeters, Petra H. M., Severi, Gianluca, Hüsing, Anika, Kaaks, Rudolf, Tjonneland, Anne, Olsen, Anja, Overvad, Kim, Bonet, Catalina, Rodriguez-Barranco, Miguel, Huerta, Jose Maria, Barricarte Gurrea, Aurelio, Bradbury, Kathryn E., Trichopoulou, Antonia, Bamia, Christina, Orfanos, Philippos, Palli, Domenico, Pala, Valeria, Vineis, Paolo, Bueno-de-Mesquita, Bas, Ohlsson, Bodil, Harlid, Sophia, van Guelpen, Bethany, Skeie, Guri, Weiderpass, Elisabete, Jenab, Mazda, Murphy, Neil, Riboli, Elio, Gunter, Marc J., Aleksandrova, Krasimira Jekova, and Tzoulaki, Ioanna
Abstract: OBJECTIVE: To systematically identify and validate published colorectal cancer risk prediction models that do not require invasive testing in two large population-based prospective cohorts. DESIGN: Models were identified through an update of a published systematic review and validated in the European Prospective Investigation into Cancer and Nutrition (EPIC) and the UK Biobank. The performance of the models to predict the occurrence of colorectal cancer within 5 or 10 years after study enrolment was assessed by discrimination (C-statistic) and calibration (plots of observed vs predicted probability). RESULTS: The systematic review and its update identified 16 models from 8 publications (8 colorectal, 5 colon and 3 rectal). The number of participants included in each model validation ranged from 41 587 to 396 515, and the number of cases ranged from 115 to 1781. Eligible and ineligible participants across the models were largely comparable. Calibration of the models, where assessable, was very good and further improved by recalibration. The C-statistics of the models were largely similar between validation cohorts with the highest values achieved being 0.70 (95% CI 0.68 to 0.72) in the UK Biobank and 0.71 (95% CI 0.67 to 0.74) in EPIC. CONCLUSION: Several of these non-invasive models exhibited good calibration and discrimination within both external validation populations and are therefore potentially suitable candidates for the facilitation of risk stratification in population-based colorectal screening programmes. Future work should both evaluate this potential, through modelling and impact studies, and ascertain if further enhancement in their performance can be obtained.
Published: 2019
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43. Comparison of prognostic models to predict the occurrence of colorectal cancer in asymptomatic individuals: a systematic literature review and external validation in the EPIC and UK Biobank prospective cohort studies

Author: Epi Methoden, Child Health, Cancer, Circulatory Health, JC onderzoeksprogramma Methodologie, Epi Kanker Team 1, JC onderzoeksprogramma Kanker, MS MDL 1, Smith, Todd, Muller, David C, Moons, Karel G M, Cross, Amanda J, Johansson, Mattias, Ferrari, Pietro, Fagherazzi, Guy, Peeters, Petra H M, Severi, Gianluca, Hüsing, Anika, Kaaks, Rudolf, Tjonneland, Anne, Olsen, Anja, Overvad, Kim, Bonet, Catalina, Rodriguez-Barranco, Miguel, Huerta, Jose Maria, Barricarte Gurrea, Aurelio, Bradbury, Kathryn E, Trichopoulou, Antonia, Bamia, Christina, Orfanos, Philippos, Palli, Domenico, Pala, Valeria, Vineis, Paolo, Bueno-de-Mesquita, Bas, Ohlsson, Bodil, Harlid, Sophia, Van Guelpen, Bethany, Skeie, Guri, Weiderpass, Elisabete, Jenab, Mazda, Murphy, Neil, Riboli, Elio, Gunter, Marc J, Aleksandrova, Krasimira Jekova, Tzoulaki, Ioanna, Epi Methoden, Child Health, Cancer, Circulatory Health, JC onderzoeksprogramma Methodologie, Epi Kanker Team 1, JC onderzoeksprogramma Kanker, MS MDL 1, Smith, Todd, Muller, David C, Moons, Karel G M, Cross, Amanda J, Johansson, Mattias, Ferrari, Pietro, Fagherazzi, Guy, Peeters, Petra H M, Severi, Gianluca, Hüsing, Anika, Kaaks, Rudolf, Tjonneland, Anne, Olsen, Anja, Overvad, Kim, Bonet, Catalina, Rodriguez-Barranco, Miguel, Huerta, Jose Maria, Barricarte Gurrea, Aurelio, Bradbury, Kathryn E, Trichopoulou, Antonia, Bamia, Christina, Orfanos, Philippos, Palli, Domenico, Pala, Valeria, Vineis, Paolo, Bueno-de-Mesquita, Bas, Ohlsson, Bodil, Harlid, Sophia, Van Guelpen, Bethany, Skeie, Guri, Weiderpass, Elisabete, Jenab, Mazda, Murphy, Neil, Riboli, Elio, Gunter, Marc J, Aleksandrova, Krasimira Jekova, and Tzoulaki, Ioanna
Published: 2019

44. Comparison of prognostic models to predict the occurrence of colorectal cancer in asymptomatic individuals: a systematic literature review and external validation in the EPIC and UK Biobank prospective cohort studies

Author: Smith, Todd, Muller, David C., Moons, Karel G. M., Cross, Amanda J., Johansson, Mattias, Ferrari, Pietro, Fagherazzi, Guy, Peeters, Petra H. M., Severi, Gianluca, Hüsing, Anika, Kaaks, Rudolf, Tjonneland, Anne, Olsen, Anja, Overvad, Kim, Bonet, Catalina, Rodriguez-Barranco, Miguel, Huerta, Jose Maria, Barricarte Gurrea, Aurelio, Bradbury, Kathryn E., Trichopoulou, Antonia, Bamia, Christina, Orfanos, Philippos, Palli, Domenico, Pala, Valeria, Vineis, Paolo, Bueno-de-Mesquita, Bas, Ohlsson, Bodil, Harlid, Sophia, van Guelpen, Bethany, Skeie, Guri, Weiderpass, Elisabete, Jenab, Mazda, Murphy, Neil, Riboli, Elio, Gunter, Marc J., Aleksandrova, Krasimira Jekova, Tzoulaki, Ioanna, MRC-PHE Centre for Environment and Health and Department of Epidemiology and Biostatistics, and Cancer Research UK
Subjects: Pronòstic mèdic, Colon, colorectal cancer, Risk Assessment, colorectal cancer screening, Europe/epidemiology, Predictive Value of Tests, Risk Factors, Càncer colorectal, Journal Article, TOOL, Humans, Comparative Study, VDP::Medisinske Fag: 700, Validation Studies, Early Detection of Cancer, Colorectal Neoplasms/epidemiology, Biological Specimen Banks, Science & Technology, Gastroenterology & Hepatology, cancer prevention, United Kingdom/epidemiology, VALUES, Research Support, Non-U.S. Gov't, Gastroenterology, 1103 Clinical Sciences, Public Health, Global Health, Social Medicine and Epidemiology, RISK SCORE, Prognosis, Colorectal cancer, United Kingdom, VDP::Medical disciplines: 700, Europe, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Asymptomatic Diseases, 1114 Paediatrics and Reproductive Medicine, epidemiology, Colorectal Neoplasms, Life Sciences & Biomedicine, medical statistics
Abstract: Objective - To systematically identify and validate published colorectal cancer risk prediction models that do not require invasive testing in two large population-based prospective cohorts. Design - Models were identified through an update of a published systematic review and validated in the European Prospective Investigation into Cancer and Nutrition (EPIC) and the UK Biobank. The performance of the models to predict the occurrence of colorectal cancer within 5 or 10 years after study enrolment was assessed by discrimination (C-statistic) and calibration (plots of observed vs predicted probability). Results - The systematic review and its update identified 16 models from 8 publications (8 colorectal, 5 colon and 3 rectal). The number of participants included in each model validation ranged from 41 587 to 396 515, and the number of cases ranged from 115 to 1781. Eligible and ineligible participants across the models were largely comparable. Calibration of the models, where assessable, was very good and further improved by recalibration. The C-statistics of the models were largely similar between validation cohorts with the highest values achieved being 0.70 (95% CI 0.68 to 0.72) in the UK Biobank and 0.71 (95% CI 0.67 to 0.74) in EPIC. Conclusion - Several of these non-invasive models exhibited good calibration and discrimination within both external validation populations and are therefore potentially suitable candidates for the facilitation of risk stratification in population-based colorectal screening programmes. Future work should both evaluate this potential, through modelling and impact studies, and ascertain if further enhancement in their performance can be obtained.
Published: 2018

45. Association of Circulating Vitamin D With Colorectal Cancer Depends on Vitamin D–Binding Protein Isoforms: A Pooled, Nested, Case-Control Study

Author: Gibbs, David Corley, primary, Song, Mingyang, primary, McCullough, Marjorie L, primary, Um, Caroline Y, primary, Bostick, Roberd M, primary, Wu, Kana, primary, Flanders, W Dana, primary, Giovannucci, Edward, primary, Jenab, Mazda, primary, Brustad, Magritt, primary, Tjønneland, Anne, primary, Perez-Cornago, Aurora, primary, Trichopoulou, Antonia, primary, Tsilidis, Konstantinos K, primary, Hultdin, Johan, primary, Barricarte Gurrea, Aurelio, primary, Bueno-de-Mesquita, Bas, primary, Mahamat-Saleh, Yahya, primary, Kühn, Tilman, primary, Gunter, Marc J, primary, Weiderpass, Elisabete, primary, and Fedirko, Veronika, primary
Published: 2019
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46. Alcohol consumption and the risk of renal cancers in the European prospective investigation into cancer and nutrition (EPIC)

Author: Françoise Clavel-Chapelon, Androniki Naska, Heiner Boeing, Kim Overvad, Petra H.M. Peeters, Ruth C. Travis, Amanda J. Cross, Verena Katzke, Anja Olsen, Darren R. Brenner, Calogero Saieva, Mattias Johansson, H. Bas Bueno-de-Mesquita, Paolo Vineis, Börje Ljungberg, Eric J. Duell, Tilman Kühn, Larraitz Arriola, Tanja Stocks, Marie-Christine Boutron-Ruault, Guy Fagherazzi, Dimitrios Trichopoulos, Nicholas J. Wareham, Rosario Tumino, Anne Tjønneland, Elio Riboli, Aurelio Barricarte Gurrea, Magdalena B. Wozniak, Sara Grioni, Salvatore Panico, Kay-Tee Khaw, Antonia Trichopoulou, Elisabete Weiderpass, Anette Hjartåker, Ghislaine Scelo, Esther Molina-Montes, Manuela M. Bergmann, Annika Steffen, Neil Murphy, Paul Brennan, Ramón Alonso De La Torre, and Carmen Santiuste
Subjects: Gynecology, Cancer Research, medicine.medical_specialty, Proportional hazards model, business.industry, Hazard ratio, Cancer, medicine.disease, European Prospective Investigation into Cancer and Nutrition, Oncology, Renal cell carcinoma, Internal medicine, medicine, Prospective cohort study, business, Kidney cancer, Cohort study
Abstract: Epidemiologic studies have reported that moderate alcohol consumption is inversely associated with the risk of renal cancer. However, there is no information available on the associations in renal cancer subsites. From 1992 through to 2010, 477,325 men and women in the European Prospective Investigation into Cancer and Nutrition cohort were followed for incident renal cancers (n=931). Baseline and lifetime alcohol consumption was assessed by country-specific, validated dietary questionnaires. Information on past alcohol consumption was collected by lifestyle questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from Cox proportional hazard models. In multivariate analysis, total alcohol consumption at baseline was inversely associated with renal cancer; the HR and 95% CI for the increasing categories of total alcohol consumption at recruitment versus the light drinkers category were 0.78 (0.62-0.99), 0.82 (0.64-1.04), 0.70 (0.55-0.90), 0.91 (0.63-1.30), respectively, (p(trend)=0.001). A similar relationship was observed for average lifetime alcohol consumption and for all renal cancer subsites combined or for renal parenchyma subsite. The trend was not observed in hypertensive individuals and not significant in smokers. In conclusion, moderate alcohol consumption was associated with a decreased risk of renal cancer. What's new? Previous studies have indicated that environmental or lifestyle factors may be involved in the etiology of renal cancer, and that moderate alcohol consumption may reduce the risk of this type of cancer. In this very large European study (nearly 500,000 subjects), the authors found that, indeed, total alcohol consumption was inversely associated with renal cancer overall (for all subsites combined), and also with cancers of the renal parenchyma.
Published: 2015

47. Plasma fetuin-A concentration, genetic variation in theAHSGgene and risk of colorectal cancer

Author: Katharina Nimptsch, Gianluca Severi, Young-Ae Lee, Ruth C. Travis, Antonia Trichopoulou, Konstantinos K. Tsilidis, Hendrik B. Bueno-de-Mesquita, Domenico Palli, Kay-Tee Khaw, Heiner Boeing, Verena Katzke, Dimitrios Trichopoulos, Marie-Christine Boutron-Ruault, Miren Dorronsoro, Juergen Janke, Elisabete Weiderpass, Rosario Tumino, Nicholas J. Wareham, Amalia Mattiello, Hanna Nyström, José Ramón Quirós, Kim Overvad, Pagona Lagiou, Aurelio Barricarte Gurrea, Antoine Racine, María Dolores Chirlaque, Sara Grioni, Anne Tjønneland, Jenny Brändstedt, Tobias Pischon, María José Sánchez, Ingrid Ljuslinder, Heinz Freisling, Mazda Jenab, Eugene Jansen, Elio Riboli, Chunsen Wu, Catalina Bonet, Krasimira Aleksandrova, Petra H.M. Peeters, Anja Olsen, So Yeon Kong, Marc J. Gunter, Rudolf Kaaks, Alessio Naccarati, and Peter D. Siersema
Subjects: Oncology, Cancer Research, medicine.medical_specialty, business.industry, Colorectal cancer, Case-control study, Single-nucleotide polymorphism, medicine.disease, European Prospective Investigation into Cancer and Nutrition, Endocrinology, Internal medicine, Relative risk, Mendelian randomization, Medicine, Risk factor, business, alpha-2-HS-glycoprotein
Abstract: Fetuin-A, also referred to as alpha 2-Heremans-Schmid glycoprotein (AHSG), is a liver protein known to inhibit insulin actions. Hyperinsulinemia is a possible risk factor for colorectal cancer; however, the role of fetuin-A in the development of colorectal cancer is unclear. We investigated the association between circulating fetuin-A and colorectal cancer risk in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition. Fetuin-A concentrations were measured in prediagnostic plasma samples from 1,367 colorectal cancer cases and 1,367 matched controls. In conditional logistic regression models adjusted for potential confounders, the estimated relative risk (95% confidence interval) of colorectal cancer per 40 mg/mL higher fetuin-A concentrations (approximately one standard deviation) was 1.13 (1.02-1.24) overall, 1.21 (1.05-1.39) in men, 1.06 (0.93-1.22) in women, 1.13 (1.00-1.27) for colon cancer and 1.12 (0.94-1.32) for rectal cancer. To improve causal inference in a Mendelian Randomization approach, five tagging single nucleotide polymorphisms of the AHSG gene were genotyped in a subset of 456 case-control pairs. The AHSG allele-score explained 21% of the interindividual variation in plasma fetuin-A concentrations. In instrumental variable analysis, genetically raised fetuin-A was not associated with colorectal cancer risk (relative risk per 40 mg/mL genetically determined higher fetuin-A was 0.98, 95% confidence interval: 0.73-1.33). The findings of our study indicate a modest linear association between fetuin-A concentrations and risk of colorectal cancer but suggest that fetuin-A may not be causally related to colorectal cancer development.
Published: 2015

48. Association of CRP genetic variants with blood concentrations of C-reactive protein and colorectal cancer risk

Author: Nimptsch, K, Aleksandrova, K, Boeing, H, Janke, J, Lee, YA, Jenab, M, Bueno-de-Mesquita, HB, Jansen, EH, Tsilidis, KK, Trichopoulou, A, Weiderpass, E, Wu, C, Overvad, K, Tjønneland, A, Boutron-Ruault, MC, Dossus, L, Racine, A, Kaaks, R, Canzian, F, Lagiou, P, Trichopoulos, D, Palli, D, Agnoli, C, Tumino, R, Vineis, P, Panico, S, Johansson, A, Van Guelpen, B, Khaw, KT, Wareham, N, Peeters, PH, Quirós, JR, Venceslá García, A, Molina-Montes, E, Dorronsoro, M, Chirlaque, MD, Barricarte Gurrea, A, Key, TJ, Duarte-Salles, T, Stepien, M, Gunter, MJ, Riboli, E, Pischon, T, Nimptsch, K, Aleksandrova, K, Boeing, H, Janke, J, Lee, Ya, Jenab, M, Bueno De Mesquita, Bh, Jansen, Eh, Tsilidis, Kk, Trichopoulou, A, Weiderpass, E, Wu, C, Overvad, K, Tj?nneland, A, Boutron Ruault, Mc, Dossus, L, Racine, A, Kaaks, R, Canzian, F, Lagiou, P, Trichopoulos, D, Palli, D, Agnoli, C, Tumino, R, Vineis, P, Panico, Salvatore, Johansson, A, Van Guelpen, B, Khaw, Kt, Wareham, N, Peeters, Ph, Quir?s, Jr, Vencesl? Garc?a, A, Molina Montes, E, Dorronsoro, M, Chirlaque, Md, Barricarte Gurrea, A, Key, Tj, Duarte Salles, T, Stepien, M, Gunter, Mj, Riboli, E, and Pischon, T.
Subjects: Adult, Male, Genotype, colorectal cancer, INFLAMMATORY MARKERS, Polymorphism, Single Nucleotide, Article, C-reactive protein, Risk Factors, COLON, Biomarkers, Tumor, Journal Article, Humans, COHORT, Comparative Study, Prospective Studies, Aged, CRP genetic variants, Research Support, Non-U.S. Gov't, WOMEN, Middle Aged, Prognosis, Cardiovascular and Metabolic Diseases, Case-Control Studies, Randomized Controlled Trial, MENDELIAN RANDOMIZATION, POPULATIONS, Female, NUTRITION, HEALTH, Colorectal Neoplasms, Follow-Up Studies
Abstract: High blood concentrations of C-reactive protein (CRP) have been associated with elevated risk of colorectal cancer in several prospective studies including the European Prospective Investigation into Cancer and Nutrition (EPIC), but it is unknown whether these observations reflect a causal relationship. We aimed to investigate whether CRP genetic variants associated with lifelong higher CRP concentrations translate into higher colorectal cancer risk. We conducted a prospective nested case-control study within EPIC including 727 cases diagnosed between 1992 and 2003 and 727 matched controls selected according to an incidence-density sampling protocol. Baseline CRP concentrations were measured in plasma samples by a high sensitivity assay. Tagging single nucleotide polymorphisms (SNPs) in the CRP gene (rs1205, rs1800947, rs1130864, rs2808630, rs3093077) were identified via HapMap. The causal effect of CRP on colorectal cancer risk was examined in a Mendelian Randomization approach utilizing multiple CRP genetic variants as instrumental variables. The SNPs rs1205, rs1800947, rs1130864 and rs3093077 were significantly associated with CRP concentrations and were incorporated in a CRP allele score which was associated with 13% higher CRP concentrations per allele count (95% confidence interval 8%, 19%). Using the CRP-score as instrumental variable, genetically 2-fold higher CRP concentrations were associated with higher risk of colorectal cancer (odds ratio 1.74, 95% confidence interval 1.06, 2.85). Similar observations were made using alternative definitions of instrumental variables. Our findings give support to the hypothesis that elevated circulating CRP may play a direct role in the etiology of colorectal cancer.
Published: 2016

49. Brote epidémico de tuberculosis

Author: Bernaola Iturbe, E., Barricarte Gurrea, A., Urtiaga Domínguez, M., Hernández Lagunas, T., and Torroba Álvarez, L.
Published: 2001
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50. An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans

Author: Rob M. van Dam, Francis S. Collins, Konstantin Strauch, Raimund Erbel, Rafn Benediktsson, Philippe Froguel, Kyle J. Gaulton, Peter Donnelly, Torben Hansen, Longda Jiang, Lennart C. Karssen, Rona J. Strawbridge, David J. Hunter, Leena Kinnunen, Thomas Meitinger, Michael Stumvoll, Stéphane Cauchi, Ching-Ti Liu, Olga McLeod, Oluf Pedersen, Michael Boehnke, Denis Rybin, Karl Gertow, Tõnu Esko, Bernhard O. Boehm, Sonali Pechlivanis, Bo Isomaa, Anne U. Jackson, Clement Ma, Yingchang Lu, Nicola D. Kerrison, Ruth J. F. Loos, Caroline S. Fox, Chiara Scapoli, Jian'an Luan, Martina Müller-Nurasyid, Domenico Palli, Anke Tönjes, Natalie R. van Zuydam, Neil Robertson, Barbara Thorand, Natalia Pervjakova, Andrew R. Wood, Karin Leander, Unnur Thorsteinsdottir, Sara M. Willems, Karen L. Mohlke, Robert A. Scott, Markus M. Nöthen, Ulf de Faire, Qi Sun, Eric Boerwinkle, Roman Wennauer, Douglas M. Ruderfer, Marika Kaakinen, Nigel W. Rayner, Jaakko Tuomilehto, Nisa M. Maruthur, Richard N. Bergman, Janina S. Ried, Himanshu Chheda, Josée Dupuis, Juan Tajes-Fernandes, Steve E. Humphries, Reedik Mägi, Gonçalo R. Abecasis, B F Voight, David Couper, Cornelia M. van Duijn, Samuli Ripatti, Yeji Lee, Heikki A. Koistinen, Christian Dina, Andres Metspalu, Lu Qi, James S. Pankow, Han Chen, Damiano Baldassarre, Mattias Frånberg, Gerald Steinbach, Inga Prokopenko, Matthias Blüher, Jose C. Florez, Julia Meyer, Niels Grarup, Anders Hamsten, Valeriya Lyssenko, James B. Meigs, Pritam Chanda, Leif Groop, Sarah Edkins, Anubha Mahajan, Gunnar Sigurðsson, Marilyn C. Cornelis, Christian Gieger, Nancy L. Pedersen, Andrew T. Hattersley, Paul W. Franks, Nicholas J. Wareham, Stefan Gustafsson, Katharine R. Owen, Peter Kovacs, Andrew D. Johnson, Lori L. Bonnycastle, Tiinamaija Tuomi, Aurelio Barricarte Gurrea, Tune H. Pers, Eric J.G. Sijbrands, Phoenix Kwan, Emmi Tikkanen, Elisabeth M. van Leeuwen, Stéphane Lobbens, Claudia Langenberg, E. Eury, Thomas W. Mühleisen, Lewin Eisele, Veikko Salomaa, Satu Mӓnnistö, Christian Fuchsberger, Evelin Mihailov, David Altshuler, Timothy M. Frayling, Peter Almgren, Harald Grallert, Hans A. Kestler, Beverley Balkau, Erik Ingelsson, Colin N. A. Palmer, Yvonne T. van der Schouw, Michael Roden, Thomas Sparsø, Karl-Heinz Jöckel, Johan G. Eriksson, Inês Barroso, John D. Eicher, Bengt Sennblad, Bruna Gigante, Andrew D. Morris, Panagiotis Deloukas, Man Li, Allan Linneberg, Astradur B. Hreidarsson, Lars Lannfelt, Elena Tremoli, Liming Liang, Omri Gottesman, Letizia Marullo, Peter S. Chines, Kari Stefansson, Mark I. McCarthy, Andrew P. Morris, Erwin P. Bottinger, Augustine Kong, Torben Jørgensen, Tanya M. Teslovich, Frank B. Hu, Dorothée Thuillier, Peter Kraft, Heiner Boeing, Laura J. Scott, Gudmar Thorleifsson, Lars Lind, John R. B. Perry, Heather M. Stringham, Susanne Moebus, Valgerdur Steinthorsdottir, Cecilia M. Lindgren, Guillaume Charpentier, Eleftheria Zeggini, Leena Peltonen, Loic Yengo, Norman Klopp, Teresa Ferreira, Christian Theil Have, Marit E. Jørgensen, Epidemiology, Erasmus MC other, Internal Medicine, Luan, Jian'an [0000-0003-3137-6337], Perry, John [0000-0001-6483-3771], Barroso, Ines [0000-0001-5800-4520], Langenberg, Claudia [0000-0002-5017-7344], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Commission of the European Communities, and Wellcome Trust
Subjects: PROVIDES, 0301 basic medicine, SUSCEPTIBILITY LOCI, endocrine system diseases, Endocrinology, Diabetes and Metabolism, PATHOPHYSIOLOGY, European Continental Ancestry Group, Medizin, Genome-wide association study, Biology, Quantitative trait locus, Bioinformatics, White People, GENETIC ARCHITECTURE, NO, Endocrinology & Metabolism, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Diabetes Mellitus, Type 2, European Continental Ancestry Group, Gene Expression Regulation, Genetic Variation, Genome-Wide Association Study, Humans, Diabetes Mellitus, Internal Medicine, Journal Article, Glucose homeostasis, Humans, 1000 Genomes Project, Allele frequency, METAANALYSIS, 11 Medical and Health Sciences, RISK, Genetics, Science & Technology, RECEPTOR, DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium, Haplotype, Genetic Variation, nutritional and metabolic diseases, Genetic architecture, 030104 developmental biology, Diabetes Mellitus, Type 2, Gene Expression Regulation, RARE VARIANTS, LOW-FREQUENCY, Life Sciences & Biomedicine, Type 2, 030217 neurology & neurosurgery, Imputation (genetics), FASTING GLUCOSE, Genome-Wide Association Study
Abstract: To characterize type 2 diabetes (T2D)-associated variation across the allele frequency spectrum, we conducted a meta-analysis of genome-wide association data from 26,676 T2D case and 132,532 control subjects of European ancestry after imputation using the 1000 Genomes multiethnic reference panel. Promising association signals were followed up in additional data sets (of 14,545 or 7,397 T2D case and 38,994 or 71,604 control subjects). We identified 13 novel T2D-associated loci (P < 5 × 10−8), including variants near the GLP2R, GIP, and HLA-DQA1 genes. Our analysis brought the total number of independent T2D associations to 128 distinct signals at 113 loci. Despite substantially increased sample size and more complete coverage of low-frequency variation, all novel associations were driven by common single nucleotide variants. Credible sets of potentially causal variants were generally larger than those based on imputation with earlier reference panels, consistent with resolution of causal signals to common risk haplotypes. Stratification of T2D-associated loci based on T2D-related quantitative trait associations revealed tissue-specific enrichment of regulatory annotations in pancreatic islet enhancers for loci influencing insulin secretion and in adipocytes, monocytes, and hepatocytes for insulin action–associated loci. These findings highlight the predominant role played by common variants of modest effect and the diversity of biological mechanisms influencing T2D pathophysiology.
Published: 2017

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