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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 (CRC). However, the association of dyslipidemia with CRC risk is controversial. 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 participants to disentangle the associations between blood lipids and CRC risk. Serum levels of total cholesterol, high- and low-density lipoprotein cholesterol (HDL-C, LDL-C), and triglyceride were measured at study baseline. Multivariable-adjusted Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

RESULTS: During a median follow-up time of 8.2 years, 3,150 incident primary CRC cases were identified. Triglyceride levels were positively, while HDL-C levels were inversely associated with CRC risk (both Ptrend <0.005). No significant associations were found for total cholesterol and LDL-C. However, among non-users of cholesterol-lowering medications, 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 CRC 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 non-users, cholesterol-lowering medication users had 15% increased CRC risk (HR =1.15; 95% CI =1.04-1.26).

CONCLUSIONS: Circulating total cholesterol, LDL-C, HDL-C and triglyceride were modestly associated with CRC risk.

IMPACT: Our findings call for careful consideration of cholesterol-lowering medication use in future studies of blood lipid-CRC associations.

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