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 3 prospective cohorts, UK Biobank, Million Women Study, and China Kadoorie Biobank. The potential impact of residual confounding was assessed by examining changes in diabetes-associated log hazard ratios (HRs) after adjustment for key confounders.

[RESULTS] In combined analyses of individual participant data from 3 studies, diabetes was positively associated with the risk of 11 cancers, most notably liver (HR = 2.04, 95% CI = 1.87 to 2.23), pancreas (HR = 1.62, 95% CI = 1.48 to 1.77), and bladder (HR = 1.44, 95% CI = 1.29 to 1.62) cancer. The positive associations of diabetes with cancers of the breast, endometrium, kidney, and esophageal 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 hazard ratio was greater in UK than Chinese adults (HR = 2.58, 95% CI = 2.28 to 2.92, vs HR = 1.61, 95% CI = 1.43 to 1.83; Phet = 2.5 x 10-6). For liver cancer, the excess risk associated with diabetes increased with increasing body mass index (Ptrend = 2.7 x 10-4) and alcohol intake (Ptrend = .02). Diabetes was inversely associated with incidence of prostate cancer (HR = 0.78, 95% CI = 0.73 to 0.85) but positively associated with mortality (HR = 1.25, 95% CI = 1.00 to 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 leukemia, but its associations with other cancers could well be explained by confounding and/or other biases.