Serum Lipid Profiles and Cholesterol-Lowering Medication Use in Relation to Subsequent Risk of Colorectal Cancer in the UK Biobank Cohort

Background: Dyslipidemia is closely associated with metabolic syndrome, a known risk factor for colorectal cancer. However, the association of dyslipidemia with colorectal cancer risk is contro-versial. Most previous studies did not consider cholesterol-lowering medication use at the time of lipid measurements, which could bias findings. Methods: We analyzed data from 384,862 UK Biobank parti-cipants to disentangle the associations between blood lipids and colorectal cancer risk. Serum levels of total cholesterol, high-and low-density lipoprotein cholesterol (HDL-C, LDL-C), and tri-glyceride were measured at study baseline. Multivariable-adjusted Cox models were used to estimate HRs and 95% confidence intervals (CI). Results: During a median follow-up time of 8.2 years, 3,150 incident primary colorectal cancer cases were identified. Triglyc-eride levels were positively, while HDL-C levels were inversely associated with colorectal cancer risk (both Ptrend < 0.005). No significant associations were found for total cholesterol and LDL-C. However, among nonusers of cholesterol-lowering medica-tions, a high total cholesterol level (> 6.7 mmol/L, HR = 1.11; 95% CI, 1.00-1.24) and LDL-C level (>4.1 mmol/L, HR = 1.11; 95% CI, 0.99-1.23) was associated with an increased colorectal cancer risk compared with the referent group (5.2-6.2 mmol/L and 2.6-3.4 mmol/L for total and LDL cholesterol, respectively). Compared with nonusers, cholesterol-lowering medication users had 15% increased colorectal cancer risk (HR = 1.15; 95% CI, 1.04-1.26). Conclusions: Circulating total cholesterol, LDL-C, HDL-C and triglyceride were modestly associated with colorectal cancer risk. Impact: Our findings call for careful consideration of cholesterol -lowering medication use in future studies of blood lipid-colorectal cancer associations.