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1. Lack of autoantibodies against collagen and related proteins in collagenous colitis

Author

Larsson JK, Roth B, Ohlsson B, and Sjöberg K

Subjects
Adult, Immunology, Colitis, Collagenous, Humans, Female, Collagen, Immunoglobulin E, Middle Aged, Colitis, Aged, Autoantibodies
Abstract

Introduction Collagenous colitis (CC) is a common cause of chronic diarrhea and is characterized by a subepithelial thickened collagen layer in the colonic mucosa. It shares many of the characteristics found in autoimmune diseases, but no autoantibodies have been identified. In CC, an imbalance in collagen turnover is evident. The purpose of the present study was to investigate whether any collagen-associated autoantibodies or other antibodies such as TPO and ASCA were present, and if levels of total IgE were increased. Methods Sera from women with active CC were analysed with ELISA for detection of autoantibodies against collagen type III and IV (Col III and IV), matrix metalloproteinase-9 (MMP-9), tissue inhibitors of metalloproteinase-1 (TIMP-1) and tenascin-C (TNC). Sera were also analysed for TPO, ASCA and total IgE. Healthy female blood donors served as controls. The cut-off value in the control group was defined as relative units > 97.5th percentile. Results Sixty-six women were included (mean age 60 years; range 31–74, mean disease duration 6 years; range 1–22). No autoantibody was significantly overexpressed in the CC population compared to controls. The mean disease duration was lower (p = 0.03) in the subjects who expressed collagen-associated autoantibodies (3.7 years; range 1–14), compared to those who did not (6.4 years; range 1–22). Treatment with budesonide was not associated with any of these autoantibodies. Conclusion No increased presence of the investigated antibodies could be found in the present study of CC. Neither could antibodies against ASCA or TPO, or elevated levels of IgE, be found. Consequently, no association was found between CC and these proteins, even though this may not be generalizable to other compounds in the collagen layer.

Published
2021

2. Inflammatory potential of the diet & risk of gastric cancer in the European Investigation into Cancer & Nutrition

Author

Agudo, A, Cayssials, V, Bonet, C, Tjønneland, A, Overvad, K, Boutron-Ruault, M-C, Affret, A, Fagherazzi, G, Katzke, V, Schubel, R, Trichopoulou, A, Karakatsani, A, La Vecchia, C, Palli, D, Grioni, S, Tumino, R, Ricceri, F, Panico, S, Bueno-de-Mesquita, B, Peeters, PH, Weiderpass, E, Skeie, G, Nøst, TH, Lasheras, C, Rodríguez-Barranco, M, Amiano, P, Chirlaque, M-D, Ardanaz, E, Ohlsson, B, Dias, JA, Nilsson, LM, Myte, R, Khaw, K-T, Perez-Cornago, A, Gunter, M, Huybrechts, I, Cross, AJ, Tsilidis, K, Riboli, E, Jakszyn, P, and Commission of the European Communities

Subjects
Adult, Inflammation, Science & Technology, Epidemiology, Nutritional Status, Breast Neoplasms, Chronic inflammation, Middle Aged, Diet, 1117 Public Health and Health Services, Breast cancer, Risk Factors, PATTERNS, Humans, Female, Prospective Studies, Prospective study, Inflammatory potential of the diet, Life Sciences & Biomedicine, Life Style, INDEX, Public, Environmental & Occupational Health
Abstract

The role of chronic inflammation on breast cancer (BC) risk remains unclear beyond as an underlying mechanism of obesity and physical activity. We aimed to evaluate the association between the inflammatory potential of the diet and risk of BC overall, according to menopausal status and tumour subtypes. Within the European Prospective Investigation into Cancer and Nutrition cohort, 318,686 women were followed for 14 years, among whom 13,246 incident BC cases were identified. The inflammatory potential of the diet was characterized by an inflammatory score of the diet (ISD). Multivariable Cox regression models were used to assess the potential effect of the ISD on BC risk by means of hazard ratios (HR) and 95% confidence intervals (CI). ISD was positively associated with BC risk. Each increase of one standard deviation (1-Sd) of the score increased by 4% the risk of BC (HR = 1.04; 95% CI 1.01–1.07). Women in the highest quintile of the ISD (indicating a most pro-inflammatory diet) had a 12% increase in risk compared with those in the lowest quintile (HR = 1.12; 95% CI 1.04–1.21) with a significant trend. The association was strongest among premenopausal women, with an 8% increased risk for 1-Sd increase in the score (HR = 1.08; 95% CI 1.01–1.14). The pattern of the association was quite homogeneous by BC subtypes based on hormone receptor status. There were no significant interactions between ISD and body mass index, physical activity, or alcohol consumption. Women consuming more pro-inflammatory diets as measured by ISD are at increased risk for BC, especially premenopausal women.

Published
2018

3. A Nested Case-Control Study of Metabolically Defined Body Size Phenotypes and Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Author

Murphy, N, Cross, A, Abubakar, M, Jenab, M, Aleksandrova, K, Boutron-Ruault, M, Dossus, L, Racine, A, Kühn, T, Katzke, V, Tjønneland, A, Petersen, K, Overvad, K, Quirós, JR, Jakszyn, P, Molina-Montes, E, Dorronsoro, M, Huerta, J, Barricarte, A, Khaw, K, Wareham, N, Travis, R, Trichopoulou, A, Lagiou, P, Trichopoulos, D, Masala, G, Krogh, V, Tumino, R, Vineis, P, Panico, S, Bueno-de-Mesquita, H, Siersema, P, Peeters, P, Ohlsson, B, Ericson, U, Palmqvist, R, Nyström, H, Weiderpass, E, Skeie, G, Freisling, H, Kong, S, Tsilidis, K, Muller, D, Riboli, E, Gunter, M, [Murphy,N, Cross,AJ, Vineis,P, Bueno-de-Mesquita,HB, Tsilidis,K, Riboli,E, Gunter,MJ] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.[Abubakar,M] Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, United Kingdom. [Jenab,M, Freisling,M, Kong,SY, Mulle,DC, Gunter,MJ] International Agency for Research on Cancer, World Health Organization, Lyon, France. [Aleksandrova,K] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Potsdam, Germany. [Boutron-Ruault,M, Dossus,L, Racine,A] Inserm, Nutrition, Hormones and Women’s Health, Centre for Research in Epidemiology and Population Health (CESP), U1018, Villejuif, France. Université Paris Sud, UMRS 1018, Villejuif, France. Institut Gustave Roussy, Villejuif, France. [Kühn,T, Katzke,VA] Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. [Tjønneland,A, Petersen,KEN] Danish Cancer Society Research Center, Copenhagen, Denmark. [Overvad,K] Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark. [Quirós,JR] Public Health Directorate, Asturias, Spain. [Jakszyn,P] Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology, Barcelona, Spain. [Molina-Montes,E] Andalusian School of Public Health, Granada, Spain. [Molina-Montes,E, Huerta,J, Barricarte,A] Biomedical Research Centre Network for Epidemiology and Public Health (CIBERESP), Madrid, Spain. [Dorronsoro,M] Public Health Direction and Biodonostia–CIBERESP, Basque Regional Health Department, Vitoria, Spain. [Huerta,J] Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain. [Barricarte,A] Navarre Public Health Institute, Pamplona, Spain. [Khaw,K] University of Cambridge, Cambridge, United Kingdom. [Wareham,N] MRC Epidemiology Unit, Cambridge, United Kingdom. [Travis,RC] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom. [Trichopoulou,A, Trichopoulos,D] Hellenic Health Foundation, Athens, Greece. [Trichopoulou,A, Lagiou,P] Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. [Trichopoulou,A, Lagiou,P, Trichopoulos,D] Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. [Lagiou,P, Trichopoulos,D] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America. [Masala,G] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Florence, Italy. [Krogh,V] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. [Tumino,R] Cancer Registry and Histopathology Unit, Civic–M.P.Arezzo Hospital, Azienda Sanitaria Provinciale di Ragusa, Italy. [Vineis,P] HuGeF Foundation, Torino, Italy. [Panico,S] Dipartimento di Medicina Clinica e Sperimentale, Federico II University, Naples, Italy. [Bueno-de- Mesquita,HB] Department of Determinants of Chronic Diseases, National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia [Bueno-de-Mesquita,HB, Siersema,PD] Department of Gastroenterology and Hepatology, University Medical Centre Utrecht, Utrecht, The Netherlands. [Peeters,PH] Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. [Ohlsson,B] Division of Internal Medicine, Department of Clinical Sciences, Skåne University Hospital, Lund University, Malmö, Sweden. [Ericson,U] Diabetes and Cardiovascular Disease–Genetic Epidemiology, Department of Clinical Sciences, Skåne University Hospital, Lund University, Malmö, Lund University, Sweden. [Palmqvist,R, Nyström,H] Medical Bioscience, Umeå University, Umeå, Sweden. [Weiderpass,E, Skeie,G] Department of Community Medicine, Faculty of Health Sciences, University of Tromsø–The Arctic University of Norway, Tromsø, Norway. [Weiderpass,E] Cancer Registry of Norway, Oslo, Norway. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Department of Genetic Epidemiology, Folkhälsan Research Center, Helsinki, Finland. [Tsilidis,K] Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece., Funding: The coordination of EPIC is financially supported by the European Commission (DGSANCO), and the International Agency for Research on Cancer., University Medical Center Utrecht, Imperial College Trust, Murphy, Neil, Cross, Amanda J, Abubakar, Mustapha, Jenab, Mazda, Aleksandrova, Krasimira, Boutron Ruault, Marie Christine, Dossus, Laure, Racine, Antoine, Kühn, Tilman, Katzke, Verena A, Tjønneland, Anne, Petersen, Kristina E. N, Overvad, Kim, Quirós, J. Ramón, Jakszyn, Paula, Molina Montes, Esther, Dorronsoro, Miren, Huerta, José María, Barricarte, Aurelio, Khaw, Kay Tee, Wareham, Nick, Travis, Ruth C, Trichopoulou, Antonia, Lagiou, Pagona, Trichopoulos, Dimitrio, Masala, Giovanna, Krogh, Vittorio, Tumino, Rosario, Vineis, Paolo, Panico, Salvatore, Bueno de Mesquita, H. Ba, Siersema, Peter D, Peeters, Petra H, Ohlsson, Bodil, Ericson, Ulrika, Palmqvist, Richard, Nyström, Hanna, Weiderpass, Elisabete, Skeie, Guri, Freisling, Heinz, Kong, So Yeon, Tsilidis, Kosta, Muller, David C, Riboli, Elio, Gunter, Marc J., Khaw, Kay-Tee [0000-0002-8802-2903], Wareham, Nicholas [0000-0003-1422-2993], and Apollo - University of Cambridge Repository

Subjects
Male, Phenomena and Processes::Genetic Phenomena::Phenotype [Medical Subject Headings], Cell- och molekylärbiologi, Obesidad, Biochemistry, Body Mass Index, Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14], Endocrinology, Odds Ratio, Insulin, Prospective Studies, Diseases::Pathological Conditions, Signs and Symptoms::Signs and Symptoms::Body Weight::Overweight [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Vital Statistics::Morbidity::Prevalence [Medical Subject Headings], Adiposity, VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, C-Peptide, Incidence, 11 Medical And Health Sciences, Oncology, Medicine, Waist Circumference, Fenotipo, Human, Logistic Model, Colon, Risk Assessment, Hyperinsulinism, Gastrointestinal Tumors, Neoplasias Colorrectales, Humans, Comparative Study, Diseases::Cardiovascular Diseases [Medical Subject Headings], Protective Factor, Cancer och onkologi, Chi-Square Distribution, Biology and Life Sciences, nutritional and metabolic diseases, Diseases::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms [Medical Subject Headings], Biomarker, Hormones, Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::Obesity [Medical Subject Headings], Prospective Studie, Logistic Models, Case-Control Studies, Cancer and Oncology, Digestive System, Biomarkers, Cell and Molecular Biology, Metabolic Processes, Physiology, Health Status, Colorectal Neoplasm, Health Statu, Risk Factors, Medicine and Health Sciences, Body Size, Multivariate Analysi, Tamaño Corporal, Enfermedades Cardiovasculares, Medicine(all), Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies [Medical Subject Headings], Research Support, Non-U.S. Gov't, Estudios de Casos y Controles, Estudios Prospectivos, Middle Aged, Multicenter Study, Europe, Phenotype, Physiological Parameters, Female, Anatomy, Colorectal Neoplasms, Case-Control Studie, Research Article, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Physical Examination::Body Constitution::Body Weights and Measures::Body Size [Medical Subject Headings], Rectal Cancer, Research Support, N.I.H., Extramural, General & Internal Medicine, Journal Article, Diseases::Nutritional and Metabolic Diseases::Metabolic Diseases::Glucose Metabolism Disorders::Hyperinsulinism [Medical Subject Headings], Obesity, Colorectal Cancer, Diabetic Endocrinology, Obesity, Metabolically Benign, Hiperinsulinismo, Risk Factor, Body Weight, Cancers and Neoplasms, Protective Factors, Gastrointestinal Tract, Metabolism, Sobrepeso, Multivariate Analysis, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, Prevalencia
Abstract

Background Obesity is positively associated with colorectal cancer. Recently, body size subtypes categorised by the prevalence of hyperinsulinaemia have been defined, and metabolically healthy overweight/obese individuals (without hyperinsulinaemia) have been suggested to be at lower risk of cardiovascular disease than their metabolically unhealthy (hyperinsulinaemic) overweight/obese counterparts. Whether similarly variable relationships exist for metabolically defined body size phenotypes and colorectal cancer risk is unknown. Methods and Findings The association of metabolically defined body size phenotypes with colorectal cancer was investigated in a case–control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Metabolic health/body size phenotypes were defined according to hyperinsulinaemia status using serum concentrations of C-peptide, a marker of insulin secretion. A total of 737 incident colorectal cancer cases and 737 matched controls were divided into tertiles based on the distribution of C-peptide concentration amongst the control population, and participants were classified as metabolically healthy if below the first tertile of C-peptide and metabolically unhealthy if above the first tertile. These metabolic health definitions were then combined with body mass index (BMI) measurements to create four metabolic health/body size phenotype categories: (1) metabolically healthy/normal weight (BMI < 25 kg/m2), (2) metabolically healthy/overweight (BMI ≥ 25 kg/m2), (3) metabolically unhealthy/normal weight (BMI < 25 kg/m2), and (4) metabolically unhealthy/overweight (BMI ≥ 25 kg/m2). Additionally, in separate models, waist circumference measurements (using the International Diabetes Federation cut-points [≥80 cm for women and ≥94 cm for men]) were used (instead of BMI) to create the four metabolic health/body size phenotype categories. Statistical tests used in the analysis were all two-sided, and a p-value of, Gunter and colleagues analyse a large European dataset to determine how body size and metabolic profile associates with the risk of developing colorectal cancer., Editors' Summary Background Colorectal cancer is the third most common cancer worldwide and is a leading cause of cancer-related death, killing around 700,000 people every year. It develops when cells in the colon (the final part of the digestive system, which is also known as the large intestine or large bowel) or the rectum (the lower end of the colon) acquire genetic changes that allow them to divide uncontrollably to form a tumor and to move around the body (metastasize). Symptoms of colorectal cancer include blood in the stool, a change in bowel habits, and unexplained weight loss. Treatments for colorectal cancer include surgery, chemotherapy, and radiation. As with other types of cancer, these treatments are more likely to be successful if started when the tumor is very small. Consequently, many countries run screening programs that use colonoscopy, the fecal occult blood test, and other tests to detect the earliest signs of colorectal cancer in apparently healthy people. Why Was This Study Done? Being obese—having too much body fat—is associated with an increased colorectal cancer risk (other risk factors include age, having a family history of colorectal cancer, and eating a high-fat, low-fiber diet). Obesity is also associated with several other chronic diseases, and recent evidence suggests that some obese individuals have a higher risk of developing these diseases than others. For example, overweight/obese individuals who have hyperinsulinemia (abnormally high blood levels of insulin; “metabolically unhealthy”) seem to have a higher risk of cardiovascular disease than their non-hyperinsulinemic (“metabolically healthy”) overweight counterparts. If certain combinations of metabolic health status and body size (“metabolically defined body size phenotypes”) are also associated with colorectal cancer, measurement of insulin levels in conjunction with body fat (adiposity) measurements such as body mass index (BMI; an indicator of body fat calculated by dividing a person’s weight in kilograms by their height in meters squared) might improve colorectal cancer risk assessment. In this nested case–control study, the researchers assess the associations between metabolically defined body size phenotypes and colorectal cancer risk. A nested case–control study identifies everyone in a group (here, participants in the European Prospective Investigation into Cancer and Nutrition [EPIC] study) who has a specific condition, identifies matched individuals in the same group without the condition, and asks whether these controls and the cases differ in terms of a specific characteristic or outcome. What Did the Researchers Do and Find? The researchers matched 737 participants in the EPIC study who developed colorectal cancer after study enrollment with 737 controls and used serum concentrations of C-peptide, a marker of insulin secretion, and BMI measurements to classify each individual as metabolically healthy/normal weight, metabolically healthy/overweight, metabolically unhealthy/normal weight, or metabolically unhealthy/overweight. Specifically, the researchers categorized people as metabolically unhealthy if they had a C-peptide level above an arbitrarily chosen cut-off value based on the distribution of C-peptide levels in the control participants and as overweight if they had a BMI of ≥25 kg/m2 (the standard definition of overweight). Compared to metabolically healthy normal weight individuals, metabolically unhealthy normal weight and overweight individuals had an increased colorectal cancer risk; metabolically healthy overweight individuals had a similar colorectal cancer risk to metabolically healthy normal weight individuals. Among overweight individuals, metabolically healthy individuals had a lower colorectal cancer risk than metabolically unhealthy individuals. Finally, similar associations were seen when the researchers used waist circumference instead of BMI as the measure of adiposity. What Do These Findings Mean? These findings suggest that normal weight individuals with hyperinsulinemia (the metabolically unhealthy normal weight phenotype) have a higher risk of colorectal cancer than normal weight individuals without hyperinsulinemia. They also suggest that metabolically unhealthy overweight individuals have a higher risk of colorectal cancer than metabolically healthy overweight individuals. The accuracy of these findings may be limited by the method the researchers used to classify individuals as hyperinsulinemic—there is no universally accepted clinical definition for using C-peptide level to diagnose hyperinsulinemia. Nevertheless, these findings suggest that the assessment of insulin levels in conjunction with adiposity measures might be a better way to assess an individual’s colorectal cancer risk than simply measuring adiposity, and might help to identify those individuals at high risk of colorectal cancer who are most likely to benefit from targeted interventions designed to prevent the onset of clinical disease. Additional Information This list of resources contains links that can be accessed when viewing the PDF on a device or via the online version of the article at http://dx.doi.org/10.1371/journal.pmed.1001988. The US National Cancer Institute provides information for patients about all aspects of colorectal cancer; it also provides more detailed information colorectal cancer for health professionals and information on cancer risk and obesity The UK National Health Service Choices website has information and personal stories about colorectal cancer and information on obesity The not-for-profit organization Cancer Research UK provides information about colorectal cancer and about the association between cancer and obesity MedlinePlus provides links to further resources about colorectal cancer and about obesity Wikipedia has a page on hyperinsulinemia (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages) More information about the EPIC study is available

Published
2016
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4. Ulcerative colitis, Crohn’s disease and other inflammatory bowel disease in a population with high exposure to per- and polyfluoroalkyl substances through drinking water

Author

Ohlsson B, Kristin Scott, Tony Fletcher, Christian H. Lindh, Kristina Jakobsson, Yiyi Xu, Eva Andersson, and Ying Li

Subjects
Global and Planetary Change, medicine.medical_specialty, Crohn's disease, education.field_of_study, Epidemiology, business.industry, Health, Toxicology and Mutagenesis, Population, Public Health, Environmental and Occupational Health, medicine.disease, Pollution, Gastroenterology, Inflammatory bowel disease, Ulcerative colitis, Internal medicine, medicine, business, education
Published
2019
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5. Detection of hepatic metastases in colorectal cancer: a prospective study of laboratory and imaging methods

Author

Ohlsson B, Karl-Göran Tranberg, Lundstedt C, Ekberg H, and Hederström E

Subjects
Adult, Aged, 80 and over, Male, Liver Neoplasms, Angiography, Middle Aged, Carcinoembryonic Antigen, Liver Function Tests, Predictive Value of Tests, Humans, Female, Prospective Studies, Colorectal Neoplasms, Tomography, X-Ray Computed, False Negative Reactions, Aged, Ultrasonography
Abstract

To assess and compare the accuracy of imaging methods (ultrasonography (US), computed tomography (CT), angiography, arterially enhanced CT with computed tomographic arterial portography (CTA)), biochemical analyses, and surgical assessment during the operation, in detecting the presence of absence of hepatic metastases in patients with colorectal cancer.Open study.University of Lund, Sweden.71 consecutive patients without clinical evidence of liver metastases at the time of the operation for removal of the primary tumour.Regular biochemical tests for five to seven years, and CT and US one year after operation in all patients without confirmed metastases.Presence or absence of hepatic metastases.Accuracy of surgical assessment, angiography, US, CT and CTA was 90, 77, 80, 82 and 83%, respectively, and corresponding predictive values of a negative test were 87, 75, 77, 80 and 84%. Measurement of bilirubin concentration and hepatic enzyme activities were not helpful, and that of carcinoembryonic antigen had an accuracy of only 70%. Accuracy and predictive values were not improved by combining tests.The accuracy of US, CT or CTA was not good enough to merit routine use before operations for colorectal cancer. They are potentially valuable for monitoring progress at follow up, but this remains to be confirmed.

Published
1993

7. Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders

Author

Eijsbouts, Chris, Zheng, Tenghao, Kennedy, Nicholas A., Bonfiglio, Ferdinando, Anderson, Carl A., Moutsianas, Loukas, Holliday, Joanne, Shi, Jingchunzi, Shringarpure, Suyash, Voda, Alexandru-Ioan, Farrugia, Gianrico, Franke, Andre, H��benthal, Matthias, Abecasis, Gon��alo, Zawistowski, Matthew, Skogholt, Anne Heidi, Ness-Jensen, Eivind, Hveem, Kristian, Esko, T��nu, Teder-Laving, Maris, Zhernakova, Alexandra, Camilleri, Michael, Boeckxstaens, Guy, Whorwell, Peter J., Spiller, Robin, McVean, Gil, D���Amato, Mauro, Jostins, Luke, Parkes, Miles, Agee, Michelle, Aslibekyan, Stella, Auton, Adam, Bell, Robert K., Bryc, Katarzyna, Clark, Sarah K., Elson, Sarah L., Fletez-Brant, Kipper, Fontanillas, Pierre, Furlotte, Nicholas A., Gandhi, Pooja M., Heilbron, Karl, Hicks, Barry, Hinds, David A., Huber, Karen E., Jewett, Ethan M., Jiang, Yunxuan, Kleinman, Aaron, Lin, Keng-Han, Litterman, Nadia K., Luff, Marie K., McCreight, Jey C., McIntyre, Matthew H., McManus, Kimberly F., Mountain, Joanna L., Mozaffari, Sahar V., Nandakumar, Priyanka, Noblin, Elizabeth S., Northover, Carrie A. M., O���Connell, Jared, Petrakovitz, Aaron A., Pitts, Steven J., Poznik, G. David, Sathirapongsasuti, J. Fah, Shastri, Anjali J., Shelton, Janie F., Tian, Chao, Tung, Joyce Y., Tunney, Robert J., Vacic, Vladimir, Wang, Xin, Zare, Amir S., Kashyap, Purna, Chang, Lin, Mayer, Emeran, Heitkemper, Margaret, Sayuk, Gregory S., Ringel-Kulka, Tamar, Ringel, Yehuda, Chey, William D., Eswaran, Shanti, Merchant, Juanita L., Shulman, Robert J., Bujanda, Luis, Garcia-Etxebarria, Koldo, Dlugosz, Aldona, Lindberg, Greger, Schmidt, Peter T., Karling, Pontus, Ohlsson, Bodil, Walter, Susanna, Faresj��, ��shild O., Simren, Magnus, Halfvarson, Jonas, Portincasa, Piero, Barbara, Giovanni, Usai-Satta, Paolo, Neri, Matteo, Nardone, Gerardo, Cuomo, Rosario, Galeazzi, Francesca, Bellini, Massimo, Latiano, Anna, Houghton, Lesley, Jonkers, Daisy, Kurilshikov, Alexander, Weersma, Rinse K., Netea, Mihai, Tesarz, Jonas, Gauss, Annika, Goebel-Stengel, Miriam, Andresen, Viola, Frieling, Thomas, Pehl, Christian, Schaefert, Rainer, Niesler, Beate, Lieb, Wolfgang, Hanevik, Kurt, Langeland, Nina, Wensaas, Knut-Arne, Litleskare, Sverre, Gabrielsen, Maiken E., Thomas, Laurent, Thijs, Vincent, Lemmens, Robin, Van Oudenhove, Lukas, Wouters, Mira, Eijsbouts C., Zheng T., Kennedy N.A., Bonfiglio F., Anderson C.A., Moutsianas L., Holliday J., Shi J., Shringarpure S., Agee M., Aslibekyan S., Auton A., Bell R.K., Bryc K., Clark S.K., Elson S.L., Fletez-Brant K., Fontanillas P., Furlotte N.A., Gandhi P.M., Heilbron K., Hicks B., Hinds D.A., Huber K.E., Jewett E.M., Jiang Y., Kleinman A., Lin K.-H., Litterman N.K., Luff M.K., McCreight J.C., McIntyre M.H., McManus K.F., Mountain J.L., Mozaffari S.V., Nandakumar P., Noblin E.S., Northover C.A.M., O'Connell J., Petrakovitz A.A., Pitts S.J., Poznik G.D., Sathirapongsasuti J.F., Shastri A.J., Shelton J.F., Tian C., Tung J.Y., Tunney R.J., Vacic V., Wang X., Zare A.S., Voda A.-I., Kashyap P., Chang L., Mayer E., Heitkemper M., Sayuk G.S., Ringel-Kulka T., Ringel Y., Chey W.D., Eswaran S., Merchant J.L., Shulman R.J., Bujanda L., Garcia-Etxebarria K., Dlugosz A., Lindberg G., Schmidt P.T., Karling P., Ohlsson B., Walter S., Faresjo A.O., Simren M., Halfvarson J., Portincasa P., Barbara G., Usai-Satta P., Neri M., Nardone G., Cuomo R., Galeazzi F., Bellini M., Latiano A., Houghton L., Jonkers D., Kurilshikov A., Weersma R.K., Netea M., Tesarz J., Gauss A., Goebel-Stengel M., Andresen V., Frieling T., Pehl C., Schaefert R., Niesler B., Lieb W., Hanevik K., Langeland N., Wensaas K.-A., Litleskare S., Gabrielsen M.E., Thomas L., Thijs V., Lemmens R., Van Oudenhove L., Wouters M., Farrugia G., Franke A., Hubenthal M., Abecasis G., Zawistowski M., Skogholt A.H., Ness-Jensen E., Hveem K., Esko T., Teder-Laving M., Zhernakova A., Camilleri M., Boeckxstaens G., Whorwell P.J., Spiller R., McVean G., D'Amato M., Jostins L., Parkes M., Eijsbouts, Chris [0000-0001-5179-0653], Anderson, Carl A. [0000-0003-1719-7009], Moutsianas, Loukas [0000-0001-5453-345X], Holliday, Joanne [0000-0003-4568-7320], Shringarpure, Suyash [0000-0001-6464-2668], Voda, Alexandru-Ioan [0000-0003-2974-6992], Farrugia, Gianrico [0000-0003-3473-5235], Hübenthal, Matthias [0000-0002-5956-3006], Abecasis, Gonçalo [0000-0003-1509-1825], Zawistowski, Matthew [0000-0002-3005-083X], Ness-Jensen, Eivind [0000-0001-6005-0729], Teder-Laving, Maris [0000-0002-5872-1850], Camilleri, Michael [0000-0001-6472-7514], Whorwell, Peter J. [0000-0002-5220-8474], Spiller, Robin [0000-0001-6371-4500], McVean, Gil [0000-0002-5012-4162], D’Amato, Mauro [0000-0003-2743-5197], Jostins, Luke [0000-0002-2475-3969], Parkes, Miles [0000-0002-6467-0631], Apollo - University of Cambridge Repository, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Translational Immunology Groningen (TRIGR), Eijsbouts, C., Zheng, T., Kennedy, N. A., Bonfiglio, F., Anderson, C. A., Moutsianas, L., Holliday, J., Shi, J., Shringarpure, S., Agee, M., Aslibekyan, S., Auton, A., Bell, R. K., Bryc, K., Clark, S. K., Elson, S. L., Fletez-Brant, K., Fontanillas, P., Furlotte, N. A., Gandhi, P. M., Heilbron, K., Hicks, B., Hinds, D. A., Huber, K. E., Jewett, E. M., Jiang, Y., Kleinman, A., Lin, K. -H., Litterman, N. K., Luff, M. K., Mccreight, J. C., Mcintyre, M. H., Mcmanus, K. F., Mountain, J. L., Mozaffari, S. V., Nandakumar, P., Noblin, E. S., Northover, C. A. M., O'Connell, J., Petrakovitz, A. A., Pitts, S. J., Poznik, G. D., Sathirapongsasuti, J. F., Shastri, A. J., Shelton, J. F., Tian, C., Tung, J. Y., Tunney, R. J., Vacic, V., Wang, X., Zare, A. S., Voda, A. -I., Kashyap, P., Chang, L., Mayer, E., Heitkemper, M., Sayuk, G. S., Ringel-Kulka, T., Ringel, Y., Chey, W. D., Eswaran, S., Merchant, J. L., Shulman, R. J., Bujanda, L., Garcia-Etxebarria, K., Dlugosz, A., Lindberg, G., Schmidt, P. T., Karling, P., Ohlsson, B., Walter, S., Faresjo, A. O., Simren, M., Halfvarson, J., Portincasa, P., Barbara, G., Usai-Satta, P., Neri, M., Nardone, G., Cuomo, R., Galeazzi, F., Bellini, M., Latiano, A., Houghton, L., Jonkers, D., Kurilshikov, A., Weersma, R. K., Netea, M., Tesarz, J., Gauss, A., Goebel-Stengel, M., Andresen, V., Frieling, T., Pehl, C., Schaefert, R., Niesler, B., Lieb, W., Hanevik, K., Langeland, N., Wensaas, K. -A., Litleskare, S., Gabrielsen, M. E., Thomas, L., Thijs, V., Lemmens, R., Van Oudenhove, L., Wouters, M., Farrugia, G., Franke, A., Hubenthal, M., Abecasis, G., Zawistowski, M., Skogholt, A. H., Ness-Jensen, E., Hveem, K., Esko, T., Teder-Laving, M., Zhernakova, A., Camilleri, M., Boeckxstaens, G., Whorwell, P. J., Spiller, R., Mcvean, G., D'Amato, M., Jostins, L., and Parkes, M.

Subjects
Male, Molecular Chaperone, Mood Disorder, 631/208/205/2138, Biology, 692/699/1503/1502/2071, Bioinformatics, Polymorphism, Single Nucleotide, Genetic pathways, 38/43, Irritable Bowel Syndrome, Cytoskeletal Protein, Genetics, medicine, Genetic predisposition, Aged, Anxiety Disorders, CD56 Antigen, Cell Adhesion Molecules, Cytoskeletal Proteins, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Guanine Nucleotide Exchange Factors, Homeodomain Proteins, Humans, Middle Aged, Molecular Chaperones, Mood Disorders, United Kingdom, Polymorphism, 692/699/476, Irritable bowel syndrome, Depression (differential diagnoses), article, Homeodomain Protein, Single Nucleotide, Guanine Nucleotide Exchange Factor, medicine.disease, Neuroticism, Biobank, Mood, Cell Adhesion Molecule, Anxiety, medicine.symptom, Anxiety Disorder, Human
Abstract

Funder: Kennedy Trust Rheumatology Research Prize Studentship, Funder: DFG Cluster of Excellence ���Precision Medicine in Chronic In-flammation��� (PMI; ID: EXC2167), Funder: EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: ���Ideas��� Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013)); doi: https://doi.org/10.13039/100011199; Grant(s): 715772, Funder: NWO-VIDI grant 016.178.056, the Netherlands Heart Foundation CVON grant 2018-27, and NWO Gravitation grant ExposomeNL, Funder: Li Ka Shing Foundation (Li Ka Shing Foundation Limited); doi: https://doi.org/10.13039/100007421, Irritable bowel syndrome (IBS) results from disordered brain���gut interactions. Identifying susceptibility genes could highlight the underlying pathophysiological mechanisms. We designed a digestive health questionnaire for UK Biobank and combined identified cases with IBS with independent cohorts. We conducted a genome-wide association study with 53,400 cases and 433,201 controls and replicated significant associations in a 23andMe panel (205,252 cases and 1,384,055 controls). Our study identified and confirmed six genetic susceptibility loci for IBS. Implicated genes included NCAM1, CADM2, PHF2/FAM120A, DOCK9, CKAP2/TPTE2P3 and BAG6. The first four are associated with mood and anxiety disorders, expressed in the nervous system, or both. Mirroring this, we also found strong genome-wide correlation between the risk of IBS and anxiety, neuroticism and depression (rg > 0.5). Additional analyses suggested this arises due to shared pathogenic pathways rather than, for example, anxiety causing abdominal symptoms. Implicated mechanisms require further exploration to help understand the altered brain���gut interactions underlying IBS.

Published
2021
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8. Loss-of-Function of the Voltage-Gated Sodium Channel NaV1.5 (Channelopathies) in Patients With Irritable Bowel Syndrome

Author

Giovanni Barbara, Yuri A. Saito, Mauro D'Amato, Greger Lindberg, Massimo Bellini, Nicholas J. Talley, Piero Portincasa, Rosario Cuomo, Weronica E. Ek, Cheryl E. Bernard, Gerardo Nardone, Aldona Dlugosz, Arthur Beyder, Pontus Karling, G. Richard Locke, Maria Gazouli, Michael J. Ackerman, Peter T. Schmidt, Bodil Ohlsson, Matteo Neri, Michael Camilleri, David J. Tester, Peter R. Strege, Felicity Enders, Paolo Usai-Satta, Francesca Galeazzi, Gianrico Farrugia, Amelia Mazzone, Beyder, A, Mazzone, A, Strege, Pr, Tester, Dj, Saito, Ya, Bernard, Ce, Enders, Ft, Ek, We, Schmidt, Pt, Dlugosz, A, Lindberg, G, Karling, P, Ohlsson, B, Gazouli, M, Nardone, GERARDO ANTONIO PIO, Cuomo, Rosario, Usai Satta, P, Galeazzi, F, Neri, M, Portincasa, P, Bellini, M, Barbara, G, Camilleri, M, Locke GR, 3rd, Talley, Nj, D'Amato, M, Ackerman, Mj, Farrugia, G., Beyder, Arthur, Mazzone, Amelia, Strege, Peter R, Tester, David J, Saito, Yuri A, Bernard, Cheryl E, Enders, Felicity T, Ek, Weronica E, Schmidt, Peter T, Dlugosz, Aldona, Lindberg, Greger, Karling, Pontu, Ohlsson, Bodil, Gazouli, Maria, Nardone, Gerardo, Usai-Satta, Paolo, Galeazzi, Francesca, Neri, Matteo, Portincasa, Piero, Bellini, Massimo, Barbara, Giovanni, Camilleri, Michael, Locke, G Richard, Talley, Nicholas J, D'Amato, Mauro, Ackerman, Michael J, and Farrugia, Gianrico

Subjects
Male, Proband, Genetics, GI Motility, Polymorphism, Voltage-Gated Sodium Channel, Adolescent, Adult, Aged, Case-Control Studies, Channelopathies, Constipation, DNA Mutational Analysis, Diarrhea, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, HEK293 Cells, Humans, Irritable Bowel Syndrome, Membrane Potentials, Middle Aged, NAV1.5 Voltage-Gated Sodium Channel, Phenotype, Prevalence, Prospective Studies, Risk Factors, Transfection, Voltage-Gated Sodium Channel Blockers, Young Adult, Gastrointestinal Motility, Mutation, Missense, Gastroenterology, Genome-wide association study, Nav1.5, HEK293 Cell, Missense mutation, Irritable bowel syndrome, biology, cardiovascular system, Case-Control Studie, Human, medicine.drug, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, Membrane Potential, Article, Channelopathie, DNA Mutational Analysi, Genetic, Mexiletine, Internal medicine, medicine, cardiovascular diseases, Hepatology, business.industry, Risk Factor, Case-control study, medicine.disease, Prospective Studie, Endocrinology, Voltage-Gated Sodium Channel Blocker, Mutation, biology.protein, Missense, business
Abstract

BACKGROUND & AIMS: SCN5A encodes the α-subunit of the voltage-gated sodium channel NaV1.5. Many patients with cardiac arrhythmias caused by mutations in SCN5A also have symptoms of irritable bowel syndrome (IBS). We investigated whether patients with IBS have SCN5A variants that affect the function of Nav1.5. METHODS: We performed genotype analysis of SCN5A in 584 persons with IBS and 1380 without (controls). Mutant forms of SCN5A were expressed in HEK-293 cells, and functions were assessed by voltage clamp analysis. A genome-wide association study (GWAS) was analyzed for an association signal for the SCN5A gene, and replicated in 1745 patients in 4 independent cohorts of IBS patients and controls. RESULTS: Missense mutations were found in SCN5A in 13/584 patients (2.2%, probands). Diarrhea-predominant IBS (IBS-D) was the most prevalent form of IBS in the overall study population (25%). However, a greater percentage of individuals with SCN5A mutations had constipation-predominant IBS (IBS-C, 31%) than IBS-D (10%, P

Published
2014
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9. Pre-diagnostic concordance with the WCRF/AICR guidelines and survival in European colorectal cancer patients: a cohort study

Author

Carla H. van Gils, E. Riboli, Christos Tsironis, Anne-Claire Vergnaud, H. Bas Bueno-de-Mesquita, Laureen Dartois, José Ramón Quirós, Veronika Fedirko, Pietro Ferrari, Teresa Norat, Pagona Lagiou, Christina C. Dahm, Giovanna Masala, Timothy J. Key, Mark J. Gunter, Maria Wennberg, Kay-Tee Khaw, Verena Katzke, Petra H.M. Peeters, Aurelio Barricarte, Heather Ward, Nicholas J. Wareham, Anne Tjønneland, Lena Maria Nilsson, Bodil Ohlsson, Valeria Pala, Laure Dossus, Antonia Trichopoulou, Tilman Kühn, Heiner Boeing, Elisabete Weiderpass, Petra A. Wark, M. Dorronsoro, Carmen Navarro, Camilla Plambeck Hansen, Genevieve Buckland, Salvatore Panico, Marie-Christine Boutron-Ruault, María José Sánchez, Paolo Vineis, Peter D. Siersema, Karin Jirström, Dora Romaguera, Rosario Tumino, Mazda Jenab, Romaguera, Dora, Ward, Heather, Wark, Petra A, Vergnaud, Anne Claire, Peeters, Petra H, van Gils, Carla H, Ferrari, Pietro, Fedirko, Veronika, Jenab, Mazda, Boutron Ruault, Marie Christine, Dossus, Laure, Dartois, Laureen, Hansen, Camilla Plambeck, Dahm, Christina Catherine, Buckland, Genevieve, Sánchez, María José, Dorronsoro, Miren, Navarro, Carmen, Barricarte, Aurelio, Key, Timothy J, Trichopoulou, Antonia, Tsironis, Christo, Lagiou, Pagona, Masala, Giovanna, Pala, Valeria, Tumino, Rosario, Vineis, Paolo, Panico, Salvatore, Bueno de Mesquita, H. Ba, Siersema, Peter D, Ohlsson, Bodil, Jirström, Karin, Wennberg, Maria, Nilsson, Lena M, Weiderpass, Elisabete, Kühn, Tilman, Katzke, Verena, Khaw, Kay Tee, Wareham, Nick J, Tjønneland, Anne, Boeing, Heiner, Quirós, José R, Gunter, Marc J, Riboli, Elio, Norat, Teresa, Department of Medical and Clinical Genetics, Medicum, BMC, BMC, Department of Epidemiology and Public Health, Imperial College London, Instituto de Investigación Sanitaria de Palma (IdISPa), Hospital Universitario Son Espases, CIBER Fisiopatología de la Obesidad y Nutrición ( (CIBEROBN)), Instituto de Salud Carlos III [Madrid] (ISC), Department of Primary Care and Public Health, Department of Epidemiology, University Medical Center [Utrecht]-Julius Center for Health Sciences and Primary Care, Nutrition and Metabolism Section, International Agency for Cancer Research (IACR), Emory University [Atlanta, GA]-Rollins School of Public Health-Winship Cancer Institute, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Section for Epidemiology, Aarhus University [Aarhus], Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology (ICO-IDIBELL)-Cancer Epidemiology Research Programme, Granada Cancer Registry, Andalusian School of Public Health [Granada], Consorcio de Investigación Biomédica en Red especializado en Epidemiología y Salud Pública (CIBERESP), Los Centros de Investigación Biomédica en Red (CIBER), Murcia Regional Health Council [Murcia], Department of Health and Social Sciences, Universidad de Murcia, Navarre Public Health Institute, Cancer Epidemiology Unit, University of Oxford, Hellenic Health Foundation, Bureau of Epidemiologic Research, Academy of Athens, Department of Hygiene, Epidemiology and Medical Statistics, Harvard School of Public Health, Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute-ISPO, Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], Cancer Registry and Histopathology Unit, Department of Oncology-Civile - M.P.Arezzo Hospital, Human Genetics Foundation (HuGeF), Università degli studi di Torino = University of Turin (UNITO), Dipartimento di Medicina Clinica e Chirurgia, University of Naples Federico II = Università degli studi di Napoli Federico II, Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya = Universiti Malaya [Kuala Lumpur, Malaisie] (UM), Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment [Bilthoven] (RIVM), Department of Gastroenterology and Hepatology, University Medical Center [Utrecht], Division of Internal Medicine, Skane University Hospital [Malmo], Lund University [Lund]-Lund University [Lund], Division of Oncology and Pathology, Lund University [Lund], Department of Public Health and Clinical Medicine, Nutritional Research, Umeå University, Arctic Research Centre, Department of Community Medicine, The Arctic University of Norway [Tromsø, Norway] (UiT), Department of Research, Cancer Registry of Norway, Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Genetic Epidemiology Group [Helsinki], Folkhälsan Research Center, Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Division of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Clinical Gerontology Unit, University of Cambridge [UK] (CAM), MRC Epidemiology Unit, University of Cambridge [UK] (CAM)-Institute of Metabolic Science, Danish Cancer Society Research Center, German Institute of Human Nutrition (DIfE) Potsdam-Rehbrücke, Public Health Directorate, Khaw, Kay-Tee [0000-0002-8802-2903], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, 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), University of Oxford [Oxford], Università degli studi di Torino (UNITO), University of Naples Federico II, University of Malaya, The Arctic University of Norway, University of Helsinki-University of Helsinki-Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki, [Romaguera,D, Ward,H, Vergnaud,A, Peeters,PH, Vineis,P, Bueno-de-Mesquita,HB, Gunter, MJ, Riboli,E, Norat,T] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Romaguera,D] Instituto de Investigación Sanitaria de Palma (IdISPa), Hospital Universitario Son Espases, Palma de Mallorca, Spain. [Romaguera,D] CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain. [Wark,PA] Global eHealth Unit, Department of Primary Care and Public Health, School of Public Health, Imperial College London, London, UK. [Peeters,PH, Gils, CH] Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. [Ferrari,P, Jenab,M] International Agency for Cancer Research (IARC), Lyon CEDEX, France. [Fedirko,V] Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, USA. [Fedirko,V] Winship Cancer Institute, Emory University, Atlanta, USA. [Boutron-Ruault,M, Dossus,L, Dartois,L] Inserm (Institut National de la Santé et de la Recherche Médicale), Centre for Research in Epidemiology and Population Health (CESP), Vaillant, Villejuif, Cedex, France. [Boutron-Ruault,M, Dartois,L] Univ Paris Sud, Villejuif, France. [Boutron-Ruault,M, Dartois,L] Gustave Roussy, Villejuif, France. [Hansen,CP, Dahm,CC] Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus C, Denmark. [Buckland,G] Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain. [Sánchez,MJ] Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs. GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain. [Sánchez,MJ, Dorronsoro,M, Navarro,C, Barricarte,A] CIBER de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain. [Dorronsoro,M] Public Health Direction and Biodonostia Basque Regional Health Department, San Sebastian, Spain. [Navarro,C] Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain. Department of Health and Social Sciences, Universidad de Murcia, Campus Universitario de Espinardo, Murcia, Spain. [Barricarte,A] Navarre Public Health Institute, Pamplona, Spain. [Key,TJ] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford UK. [Trichopoulou,A, Tsironis,C] Hellenic Health Foundation, Athens, Greece . [Trichopoulou,A, Lagiou,P] Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. [Lagiou,P] Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Athens, Greece. [Lagiou,P] Department of Epidemiology, Harvard School of Public Health, Boston, USA. [Masala,G] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute – ISPO, Florence, Italy. [Pala,V] Epidemiology and Prevention Unit, Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy. [Tumino,R] Cancer Registry and Histopathology Unit, 'Civic – M.P. Arezzo' Hospital, Ragusa, Italy. [Vineis,P] HuGeF Foundation, Turin, Italy. [Panico,S] Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy. [Bueno-de-Mesquita,HB] Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven The Netherlands. [Bueno-de-Mesquita,HB, Siersema,PD] Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands. [Bueno-de-Mesquita,HB] Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. [Ohlsson,B] Division of Internal Medicine, Department of Clinical Sciences, Skane University Hospital, Malmo, Lund University, Lund, Sweden. [Jirström,K] Department of Clinical Sciences, Division of Oncology and Pathology, Lund University, Lund, Sweden. [Wennberg,M] Public Health and Clinical Medicine, Nutritional Research, Umeå University, Umeå, Sweden. [Nilsson,LM] Arctic Research Centre, Umeå University, Umeå, Sweden. [Weiderpass,E] Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, ISM - Universitetet i Tromsø, Tromsø, Norway. Department of Research, Cancer Registry of Norway, Majorstuen Oslo, Norway. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Department of Genetic Epidemiology, Folkhälsan Research Center, Folkhälsan Research Center, Biomedicum 1, University of Helsinki, Helsinki, Finland. [Kühn,T, Katzke,V] German Cancer Research Center (DKFZ), Division of Cancer Epidemiology Im Neuenheimer Feld 581, Heidelberg, Germany. [Khaw,K] University of Cambridge School of Clinical Medicine, Clinical Gerontology Unit Box 251, Addenbrooke’s Hospital, Cambridge, UK. [Wareham,NJ] MRC Epidemiology Unit, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK. [Tjønneland,A] Danish Cancer Society Research Center, Copenhagen, Denmark. [Boeing,H] Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany. [Quirós,JR] Public Health Directorate, Oviedo Asturias, Spain., This study was funded by the World Cancer Research Fund (WCRF) International Regular Grant Programme (Grant number 2009/44). Dora Romaguera holds a Ramon y Cajal contract (Ministerio de Economía y Competitividad, Spain and European Regional Development Fund, RYC-2011-08796). In addition, EPIC investigators acknowledge funding from the following agencies: Europe Against Cancer Program of the European Commission (SANCO), German Cancer Aid, German Cancer Research Center (DKFZ), German Federal Ministry of Education and Research (BMBF), Danish Cancer Society, Catalan Institute of Oncology, Spain, Health Research Fund (FIS) of the Spanish Ministry of Health, Spanish Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236) and Navarra, ISCIII RCESP exp. C03/09 and ISCIII RETICC RD06/0020/0091, Spain, Cancer Research UK, Medical Research Council, United Kingdom, The Hellenic Health Foundation, Greece, Italian Association for Research on Cancer (AIRC), Italian National Research Council, Fondazione-Istituto Banco Napoli, Italy, Dutch Ministry of Public Health, Welfare and Sports, Dutch Prevention Funds, LK Research Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), The Netherlands, Swedish Cancer Society, Swedish Scientific Council, Regional Government of Skåne, Sweden, Helga—Nordic Center of Excellence Programme in Nutrition and Health, French League against Cancer (LNCC), National Institute for Health and Medical Research (INSERM), France, Mutuelle Générale de l'Education Romaguera et al. BMC Medicine (2015) 13:107 Page 10 of 12 Nationale (MGEN), France, 3 M Co., France, Gustave Roussy Institute (IGR), France, and and General Councils of France. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Subjects
Male, physical activity, 0302 clinical medicine, estudios prospectivos, Prospective Studies, estudios de cohortes, mediana edad, Aged, 80 and over, anciano, Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Motor Activity [Medical Subject Headings], dieta, Incidence, Hazard ratio, COLON-CANCER, General Medicine, adulto, 3. Good health, Näringslära, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, estilo de vida, Cohort, Dieta, Estilo de Vida, RESEARCH FUND/AMERICAN INSTITUTE, Cohort study, Human, medicine.medical_specialty, Concordance, European Continental Ancestry Group, DIAGNOSIS, incidencia, White People, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Càncer colorectal, Neoplasias Colorrectales, BREAST-CANCER, Humans, Life Style, Aged, Cancer prevention, Proportional hazards model, Physical activity, 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], weight, LIFE-STYLE FACTORS, Colorectal cancer, REPRODUCTIVE HISTORY, Prospective Studie, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies [Medical Subject Headings], Cancer and Oncology, Proportional Hazards Model, grupo de ascendencia continental europea, Estudios de Cohortes, Gerontology, cumplimiento del paciente, Survival, modelos de riesgos proporcionales, VDP::Medisinske Fag: 700::Helsefag: 800::Epidemiologi medisinsk og odontologisk statistikk: 803, [SDV]Life Sciences [q-bio], humanos, Colorectal Neoplasm, Alcohol consumption, Breast cancer, Prospective study, Named Groups::Persons::Survivors [Medical Subject Headings], Cohort Studies, 030212 general & internal medicine, Prospective cohort study, Non-U.S. Gov't, 2. Zero hunger, Medicine(all), RISK, Nutrition and Dietetics, Healthy lifestyle, Diet, Weight, Research Support, Non-U.S. Gov't, Public Health, Global Health, Social Medicine and Epidemiology, Middle Aged, European Prospective Investigation into Cancer and Nutrition, VDP::Medical disciplines: 700::Health sciences: 800::Epidemiology medical and dental statistics: 803, NUTRITION, Female, Colorectal Neoplasms, Research Article, Adult, neoplasias colorrectales, 3122 Cancers, RECREATIONAL PHYSICAL-ACTIVITY, Other Research Radboud Institute for Molecular Life Sciences [Radboudumc 0], colorectal cancer, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings], Research Support, survival, Sobrevivientes, healthy lifestyle, Internal medicine, medicine, Journal Article, Proportional Hazards Models, Actividad Motora, business.industry, Physical fitness, BODY-MASS INDEX, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Other Clinical Medicine, 3121 General medicine, internal medicine and other clinical medicine, Patient Compliance, Cohort Studie, business, diet, Condició física
Abstract

Background: Cancer survivors are advised to follow lifestyle recommendations on diet, physical activity, and body fatness proposed by the World Cancer Research Fund/American Institute of Cancer Research (WCRF/AICR) for cancer prevention. Previous studies have demonstrated that higher concordance with these recommendations measured using an index score (the WCRF/AICR score) was associated with lower cancer incidence and mortality. The aim of this study was to evaluate the association between pre-diagnostic concordance with WCRF/AICR recommendations and mortality in colorectal cancer (CRC) patients. Methods: The association between the WCRF/AICR score (score range 0-6 in men and 0-7 in women; higher scores indicate greater concordance) assessed on average 6.4 years before diagnosis and CRC-specific (n = 872) and overall mortality (n = 1,113) was prospectively examined among 3,292 participants diagnosed with CRC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (mean follow-up time after diagnosis 4.2 years). Multivariable Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality. Results: The HRs (95% CIs) for CRC-specific mortality among participants in the second (score range in men/women: 2.25-2.75/3.25-3.75), third (3-3.75/4-4.75), and fourth (4-6/5-7) categories of the score were 0.87 (0.72-1.06), 0.74 (0.61-0.90), and 0.70 (0.56-0.89), respectively (P for trend, We would like to acknowledge the contribution of all participants in the study. This study was funded by the World Cancer Research Fund (WCRF) International Regular Grant Programme (Grant number 2009/44). Dora Romaguera holds a Ramon y Cajal contract (Ministerio de Economia y Competitividad, Spain and European Regional Development Fund; RYC-2011-08796). In addition, EPIC investigators acknowledge funding from the following agencies: Europe Against Cancer Program of the European Commission (SANCO); German Cancer Aid; German Cancer Research Center (DKFZ); German Federal Ministry of Education and Research (BMBF); Danish Cancer Society; Catalan Institute of Oncology, Spain; Health Research Fund (FIS) of the Spanish Ministry of Health; Spanish Regional Governments of Andalucia, Asturias, Basque Country, Murcia (no. 6236) and Navarra; ISCIII RCESP exp. C03/09 and ISCIII RETICC RD06/0020/0091, Spain; Cancer Research UK; Medical Research Council, United Kingdom; The Hellenic Health Foundation, Greece; Italian Association for Research on Cancer (AIRC); Italian National Research Council; Fondazione-Istituto Banco Napoli, Italy; Dutch Ministry of Public Health, Welfare and Sports, Dutch Prevention Funds, LK Research Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), The Netherlands; Swedish Cancer Society; Swedish Scientific Council; Regional Government of Skane, Sweden; Helga-Nordic Center of Excellence Programme in Nutrition and Health; French League against Cancer (LNCC); National Institute for Health and Medical Research (INSERM), France; Mutuelle Generale de l'Education Nationale (MGEN), France; 3 M Co., France; Gustave Roussy Institute (IGR), France; and General Councils of France.

Published
2014
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