The class
Mendelian randomization finds CETP inhibition uniquely associated with increased breast cancer risk among lipid-lowering drug targets (Cancer Causes Control 2024)
Original title: Circulating lipids, lipid-lowering drug targets, and breast cancer risk: Comprehensive evidence from Mendelian randomization and summary data-based Mendelian randomization
Using Mendelian randomization and summary-data-based Mendelian randomization, researchers examined causal relationships between circulating lipids, lipid-lowering drug targets and breast cancer risk. Higher LDL cholesterol, HDL cholesterol, total cholesterol and apolipoprotein A-I were each associated with increased breast cancer risk, while triglycerides were associated with reduced risk. For every 1 mg/dL decrease in LDL cholesterol, genetically proxied HMGCR, NPC1L1 and PCSK9 inhibition were each associated with reduced breast cancer risk, but CETP inhibition was associated with INCREASED breast cancer risk (odds ratio 1.194), an effect that was even larger for estrogen-receptor-negative breast cancer (odds ratio 1.465). The authors conclude that while HMGCR, NPC1L1, PCSK9 and APOB may be effective breast cancer prevention strategies, CETP-targeted lipid-lowering therapy may potentially increase breast cancer risk.
Original abstract
Background: Breast cancer (BC) is the most common and fatal cancer among women, yet the causal relationship between circulating lipids, lipid-lowering drugs, and BC remains unclear.
Methods: Mendelian randomization (MR) and summary data-based MR (SMR) analysis are used to explore the causal relationship between plasma lipids, lipid-lowering drug targets, and BC.
Results: The result of MR suggested that per mg/dL higher levels of LDL-C (OR = 1.045, FDR = 0.023), HDL-C (OR = 1.079, FDR = 0.003), TC (OR = 1.043, FDR = 0.026), and APOA-I (OR = 1.085, FDR = 2.64E-04) were associated with increased BC risk, while TG was associated with reduced BC risk (OR = 0.926, FDR = 0.003). Per mg/dL higher levels of HDL-C (OR = 1.080, FDR = 0.011) and APOA-I (OR = 1.083, FDR = 0.002) were associated with increased ER+BC risk, while TG was associated with reduced ER+BC risk (OR = 0.909, FDR = 0.002). For every per 1 mg/dL decrease in LDL, HMGCR (OR: 0.839; FDR = 0.016), NPC1L1 (OR: 0.702; FDR = 0.004), and PCSK9 (OR: 0.916; FDR = 0.026) inhibition were associated with reduced BC risk, whereas CETP inhibition (OR: 1.194; FDR = 0.026) was associated with increased BC risk. For every per 1 mg/dL decrease in LDL, HMGCR (OR: 0.822; FDR = 0.023), NPC1L1 (OR: 0.633; FDR = 2.37E-03), and APOB inhibition (OR: 0.816; FDR = 1.98E-03) were associated with decreased ER-BC risk, while CETP inhibition (OR: 1.465; FDR = 0.011) was associated with increased ER-BC risk. SMR analysis indicated that HMGCR was associated with increased BC risk (OR: 1.112; p = 0.044).
Conclusion: Lipids are associated with the BC risk, and lipid-lowering drugs targets HMGCR, NPC1L1, PCSK9, and APOB may be effective strategies for preventing BC. However, lipid-lowering drugs target CETP may potentially increase BC risk.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.