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4. Lifestyle factors and risk of multimorbidity of cancer and cardiometabolic diseases: a multinational cohort study

Author

Freisling, Heinz, Viallon, Vivian, Lennon, Hannah, Bagnardi, Vincenzo, Ricci, Cristian, Butterworth, Adam S., Sweeting, Michael, Muller, David, Romieu, Isabelle, Bazelle, Pauline, Kvaskoff, Marina, Arveux, Patrick, Severi, Gianluca, Bamia, Christina, Kühn, Tilman, Kaaks, Rudolf, Bergmann, Manuela, Boeing, Heiner, Tjønneland, Anne, Olsen, Anja, Overvad, Kim, Dahm, Christina C., Menéndez, Virginia, Agudo, Antonio, Sánchez, Maria-Jose, Amiano, Pilar, Santiuste, Carmen, Gurrea, Aurelio Barricarte, Tong, Tammy Y. N., Schmidt, Julie A., Tzoulaki, Ioanna, Tsilidis, Konstantinos K., Ward, Heather, Palli, Domenico, Agnoli, Claudia, Tumino, Rosario, Ricceri, Fulvio, Panico, Salvatore, Picavet, H. Susan J., Bakker, Marije, Monninkhof, Evelyn, Nilsson, Peter, Manjer, Jonas, Rolandsson, Olov, Thysell, Elin, Weiderpass, Elisabete, Jenab, Mazda, Riboli, Elio, Vineis, Paolo, Danesh, John, Wareham, Nick J., Gunter, Marc J., and Ferrari, Pietro

Published
2020
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5. Lifestyle factors and risk of multimorbidity of cancer and cardiometabolic diseases: A multinational cohort study

Author

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, Freisling H., Viallon V., Lennon H., Bagnardi V., Ricci C., Butterworth A. S., 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. C., Menendez V., Agudo A., Sanchez M. -J., Amiano P., Santiuste C., Gurrea A. B., Tong T. Y. N., Schmidt J. A., Tzoulaki I., Tsilidis K. K., Ward H., Palli D., Agnoli C., Tumino R., Ricceri F., Panico S., Picavet H. S. J., Bakker M., Monninkhof E., Nilsson P., Manjer J., Rolandsson O., Thysell E., Weiderpass E., Jenab M., Riboli E., Vineis P., Danesh J., Wareham N. J., Gunter M. J., Ferrari P., 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, Freisling H., Viallon V., Lennon H., Bagnardi V., Ricci C., Butterworth A. S., 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. C., Menendez V., Agudo A., Sanchez M. -J., Amiano P., Santiuste C., Gurrea A. B., Tong T. Y. N., Schmidt J. A., Tzoulaki I., Tsilidis K. K., Ward H., Palli D., Agnoli C., Tumino R., Ricceri F., Panico S., Picavet H. S. J., Bakker M., Monninkhof E., Nilsson P., Manjer J., Rolandsson O., Thysell E., Weiderpass E., Jenab M., Riboli E., Vineis P., Danesh J., Wareham N. J., Gunter M. J., and Ferrari P.

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

Published
2020

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

Author

Freisling, H. Viallon, V. Lennon, H. Bagnardi, V. Ricci, C. Butterworth, A.S. Sweeting, M. Muller, D. Romieu, I. Bazelle, P. Kvaskoff, M. Arveux, P. Severi, G. Bamia, C. Kühn, T. Kaaks, R. Bergmann, M. Boeing, H. Tjønneland, A. Olsen, A. Overvad, K. Dahm, C.C. Menéndez, V. Agudo, A. Sánchez, M.-J. Amiano, P. Santiuste, C. Gurrea, A.B. Tong, T.Y.N. Schmidt, J.A. Tzoulaki, I. Tsilidis, K.K. Ward, H. Palli, D. Agnoli, C. Tumino, R. Ricceri, F. Panico, S. Picavet, H.S.J. Bakker, M. Monninkhof, E. Nilsson, P. Manjer, J. Rolandsson, O. Thysell, E. Weiderpass, E. Jenab, M. Riboli, E. Vineis, P. Danesh, J. Wareham, N.J. Gunter, M.J. Ferrari, P.

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. © 2020 The Author(s).

Published
2020

7. Is It Being Overdiagnosed? Feline Pancreatitis

Author

Bazelle, Julien and Watson, Penny

Abstract

In recent years, increased awareness of feline pancreatitis by the veterinary profession and improved diagnostic modalities have led to an increased frequency of diagnosis of pancreatitis in this species. Consequently, pancreatic diseases, especially chronic pancreatitis, are considered highly prevalent, even in populations of apparently healthy individuals. This prevalence has led to the suspicion that the condition may be overdiagnosed. This article summarizes the difficulties of diagnosis of acute and chronic pancreatitis, assesses the reasons why this is a challenging disease to recognize, and considers whether these difficulties could result in either overdiagnosis or underdiagnosis.

Published
2020
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9. 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
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10. Cancer selective cell death induction by a bivalent CK2 inhibitor targeting the ATP site and the allosteric αD pocket.

Author

Bancet A, Frem R, Jeanneret F, Mularoni A, Bazelle P, Roelants C, Delcros JG, Guichou JF, Pillet C, Coste I, Renno T, Battail C, Cochet C, Lomberget T, Filhol O, and Krimm I

Abstract

Although the involvement of protein kinase CK2 in cancer is well-documented, there is a need for selective CK2 inhibitors suitable for investigating CK2 specific roles in cancer-related biological pathways and further exploring its therapeutic potential. Here, we report the discovery of AB668, an outstanding selective inhibitor that binds CK2 through a bivalent mode, interacting both at the ATP site and an allosteric αD pocket unique to CK2. Using caspase activation assay, live-cell imaging, and transcriptomic analysis, we have compared the effects of this bivalent inhibitor to representative ATP-competitive inhibitors, CX-4945, and SGC-CK2-1. Our results show that in contrast to CX-4945 or SGC-CK2-1, AB668, by targeting the CK2 αD pocket, has a distinct mechanism of action regarding its anti-cancer activity, inducing apoptotic cell death in several cancer cell lines and stimulating distinct biological pathways in renal cell carcinoma., Competing Interests: The authors A.B. and I.K. declare the following competing financial interest(s): A.B. and I.K. acknowledge greater than 5% ownership of KAIROS DISCOVERY, a company that is developing small molecules as targeted cancer therapies. The other authors declare no competing interests. The authors A.B., T.L., C.C., O.F., and I.K. declare that they are authors of a related patent WO2022008475. The other authors and their immediate family members, have no related patents to declare., (© 2024 The Authors.)

Published
2024
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