Low-Density Lipoprotein Cholesterol and the Risk of Cancer: A Mendelian Randomization Study

摘要: Background Low plasma levels of low-density lipoprotein (LDL) cholesterol are associated with an increased risk cancer, but whether this association is causal unclear. Methods We studied 10 613 participants in the Copenhagen City Heart Study (CCHS) and 59 566 General Population Study, 6816 whom had developed cancer by May 2009. Individuals were genotyped for PCSK9 R46L (rs11591147), ABCG8 D19H (rs11887534), APOE R112C (rs429358) R158C (rs7412) polymorphisms, all which lifelong reduced LDL levels. Plasma was calculated using Friedewald equation samples triglyceride level less than 354 mg/dL measured directly colorimetry higher Risk estimated prospectively Cox proportional hazards regression analyses cross-sectionally logistic analyses. Causality instrumental variable analysis. All statistical tests two-sided. Results In CCHS, compared greater 66th percentile (>158 mg/dL), those lower 10th (<87 mg/dL) a 43% increase (95% confidence interval [CI] = 15% to 79% increase) cancer. The polymorphisms up 38% reduction CI 36% 41% reduction) not odds ratio 50% due genotypes both studies combined 0.96 0.87 1.05), whereas hazard CCHS 1.10 1.01 1.21) (P vs observed .03). Conclusion robustly genetically decreased not. This finding suggests that low per se do cause