Circulating lipids, lipid-lowering drug targets, and breast cancer risk: Comprehensive evidence from Mendelian randomization and summary data-based Mendelian randomization
Menée à l'aide d'une méthode de randomisation mendélienne et de données, cette étude analyse l'association entre le niveau des lipides plasmatiques, l'utilisation de médicaments hypolipémiants et le risque de cancer du sein
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.