Lifestyle factors and risk of multimorbidity of cancer and cardiometabolic diseases: a multinational cohort study
Authors: 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. , Ferrari Pietro 
Published: January 2020

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.