Prospective associations of diabetes with 15 cancers in 2.2 million UK and Chinese adults.

BACKGROUND Diabetes has been associated with the risk of numerous cancers but the causal relevance of many of these associations remains unclear. METHODS We investigated associations between diabetes and risks of 15 cancers using Cox-regression and individual-level data from 2.2 million adults (334,978 incident cancer cases) in three prospective cohorts, UK Biobank (UKB), Million Women Study (MWS), and China Kadoorie Biobank (CKB). The potential impact of residual confounding was assessed by examining changes in diabetes-associated log-HRs after adjustment for key confounders. RESULTS In combined analyses of individual participant data from three studies, diabetes was positively associated with the risk of 11 cancers, most notably liver (HR = 2.04, 95%CI: 1.87-2.23), pancreas (1.62, 1.48-1.77) and bladder (1.44, 1.29-1.62) cancer. The positive associations of diabetes with cancers of the breast, endometrium, kidney, and oesophageal adenocarcinoma, were substantially attenuated (>50%) after adjustment for confounders. The risks were similar in UK and Chinese populations except for liver cancer, for which the adjusted HR was greater in UK than Chinese adults (2.58 [2.28-2.92] vs 1.61 [1.43-1.83]; Phet=2.5x10-6). For liver cancer, the excess risk associated with diabetes increased with increasing BMI (Ptrend=2.7x10-4) and alcohol intake (Ptrend=0.02). Diabetes was inversely associated with incidence of prostate cancer (0.78 [0.73-0.85]) but positively associated with mortality (1.25 [1.00-1.55]). CONCLUSIONS Diabetes increases the risk of liver, pancreatic, and bladder cancer in UK and Chinese populations. It may also have a lesser effect on stomach, colorectal cancer, and leukaemia but its associations with other cancers could well be explained by confounding and/or other biases.