Type 2 diabetes, adiposity and cancer morbidity and mortality risk taking into account competing risk of noncancer deaths in a prospective cohort setting

Type 2 diabetes (T2D) and adiposity associate with increased risk of several cancers, but the impact of competing risk of noncancer deaths on these associations is not known. We prospectively examined participants in the Malmö Diet and Cancer Study aged 44-73 years with no history of cancer at baseline (n = 26,953, 43% men). T2D was ascertained at baseline and during follow-up, and body mass index (BMI) and waist circumference (WC) at baseline. Multivariable cause-specific hazard ratios (HR) and subdistribution hazard ratios (sHR), taking into account noncancer deaths, were estimated using Cox- and competing risk regression. During follow-up (mean 17 years), 7,061 incident cancers (3,220 obesity-related cancer types) and 2,848 cancer deaths occurred. BMI and WC were associated with increased risk of obesity-related cancer incidence and cancer mortality. In T2D subjects, risk of obesity-related cancer was elevated among men (HR = 1.31, 95% CI: 1.12-1.54; sHR = 1.29, 95% CI: 1.10-1.52), and cancer mortality among both men and women (HR = 1.34, 95% CI: 1.20-1.49; sHR = 1.30, 95% CI: 1.16-1.45). There was no elevated actual risk of cancer death in T2D patients with long disease duration (sHR = 1.00, 95% CI: 0.83-1.20). There was a significant additive effect of T2D and adiposity on risk of obesity-related cancer and cancer mortality. In conclusion, detection bias may partially explain the increased risk of cancer morbidity among T2D patients. Both excess risk of competing events among patients with T2D and depletion of susceptibles due to earlier cancer detection will lower the actual risk of cancer, particularly with longer diabetes duration and at older ages.