Objective To examine separate and joint associations between pre-existing cardiometabolic comorbidities and all cause and cause specific mortality in adults with cancer.

Design Multinational cohort study.

Setting Seven European countries from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, 1 January 1992 to 31 December 2013.

Participants 26 987 participants (54% women) who developed a first primary cancer. 2113 had a history of type 2 diabetes, 1529 had a history of cardiovascular disease, and 531 had a history of both, at the time of diagnosis of cancer.

Main outcome measures Hazard ratios (95% confidence intervals, CIs) for associations between pre-existing cardiometabolic comorbidities and all cause and cause specific mortality in adults with cancer, estimated with multivariable Cox regression models. Associations were also estimated by groups of five year relative survival of cancer (survival ≤40%, 40-80%, and ≥80%) according to Surveillance, Epidemiology, and End Results (SEER) statistics, and for the most common site specific cancers.

Results At the time of diagnosis of cancer, 84.5% (n=22 814) of participants had no history of a cardiometabolic disease, 7.8% (n=2113) had a history of type 2 diabetes, 5.7% (n=1529) had a history of cardiovascular disease, and 2.0% (n=531) had a history of both cardiovascular disease and type 2 diabetes. 12 782 deaths (10 492 cancer deaths) occurred over a mean follow-up period of 7.2 years. After multivariable adjustments, pre-existing comorbidities were positively associated with all cause mortality, with hazard ratios 1.25 (95% CI 1.17 to 1.34), 1.30 (1.21 to 1.39), and 1.60 (1.42 to 1.80) for participants with type 2 diabetes, cardiovascular disease, or both, respectively, compared with participants with no cardiometabolic comorbidity. Corresponding hazard ratios for cancer specific mortality were 1.13 (95% CI 1.05 to 1.22), 1.13 (1.04 to 1.23), and 1.33 (1.16 to 1.53), respectively. Associations for all cause mortality were stronger among participants with cancers with a five year relative survival ≥80%. In a subsample, duration of type 2 diabetes (P_interaction=0.73) or cardiovascular disease (P_interaction=0.24), categorised as <5 years or ≥5 years, did not modify associations between these comorbidities and all cause mortality.

Conclusions In this study, cardiovascular disease or type 2 diabetes, or a combination of both, before a diagnosis of cancer, was associated with increased mortality (all cause mortality, and cancer and cardiovascular disease specific mortality). These findings support a direct role of cardiometabolic comorbidities on the prognosis of cancer.