Causal relevance of circulating high-density lipoprotein cholesterol with cancer: a Mendelian randomization meta-analysis

We summarized published data on the associations of apolipoprotein E (APOE) gene epsilon 2/epsilon 3/epsilon 4 polymorphism with both cancer risk and circulating lipid profiles, aiming to examine the causal relevance between lipids and cancer risk. Article identification and data abstraction were conducted in duplicate and independently by two authors. Data were analyzed by STATA software. Twenty-five articles that examined the associations of APOE gene epsilon 2/epsilon 3/epsilon 4 polymorphism with either cancer risk (n = 22) or circulating lipid changes (n = 4) were eligible. The presence of epsilon 2 and epsilon 4 alleles showed no overall associations with overall cancer risk when compared with epsilon 3 allele. The epsilon 4 allele was significantly associated with 1.40-fold (odds ratio or OR = 1.40; 95% confidence interval or CI: 1.00-1.94; P = 0.047) increased risk of developing cancer in Asian populations, and the presence of heterogeneity was low (I-2 = 37.6%). Carriers of epsilon 3 epsilon/4 genotype had a significant reduction in circulating HDL-C (WMD = -2.62; 95% CI: -4.19 to -1.04; P = 0.001) without heterogeneity (I-2 = 16.6%). The predicted odds of having cancer for 1 mg/dL reduction in circulating HDL-C was 1.14 (95% CI: 1.00 to 1.89). The findings of this Mendelian randomization meta-analysis demonstrate that reduced circulating HDL-C might be a potentially causal risk factor for the development of overall cancer in Asians.