Synergistic effects of low LDL cholesterol with other factors for the risk of cancer in type 2 diabetes: the Hong Kong Diabetes Registry

We have reported associations of cancer with low triglyceride and high high-density lipoprotein cholesterol (HDL-C) as well as co-presence of low low-density lipoprotein cholesterol (LDL-C) and albuminuria in type 2 diabetes (T2D). This analysis aims to test (1) whether low LDL-C and low triglyceride have synergistic effects to increase cancer risk in T2D and (2) whether high HDL-C enhances the effect of co-presence of low LDL-C and albuminuria on cancer risk. A prospective cohort of patients with T2D, established within the Prince of Wales Hospital, was used in the analysis. A total of 3,476 T2D patients in Hong Kong enrolled between 1996 and 2005, free of cancer at enrolment and not using statins or fibrates within 2.5 years before enrolment and during follow-up, were followed until 2005. The study measured additive interactions of low LDL-C with other factors for cancer using relative excess risk due to interaction (RERI) and attributable proportion due to interaction (AP). A statistically significant RERI > 0 or AP > 0 indicates additive interaction. During 5.11 years of follow-up, 199 patients developed cancer. Co-presence of triglyceride <1.70 mmol/L and LDL-C < 2.80 mmol/L was associated with increased cancer risk (multivariable hazard ratio [HR]:2.13, P = 0.0008) with significant interaction. Co-presence of HDL-C >= 1.30 mmol/L and LDL-C < 2.80 mmol/L plus albuminuria was also associated with increased cancer risk (HR: 3.84, P < 0.0001) with significant interaction. In T2D, low triglyceride may potentiate cancer risk associated with low LDL-C while high HDL-C enhances the synergistic effect of low LDL-C with albuminuria towards increased cancer risk.