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Background: Statin use for cancer prevention has raised wide attention but the conclusions are still controversial. Whether statins use have exact causal effects on cancer prevention remains unclear.

Methods: Based on the Genome-Wide Association Studies (GWAS) datasets from the large prospective UK Biobank and other consortium databases, two-sample mendelian randomization (MR) analysis was conducted to explore the causal effects of statins use on varied site-specific cancer risks. Five MR methods were applied to investigate the causality. The stability, heterogeneity, and pleiotropy of MR results were also evaluated.

Results: The atorvastatin use could increase the risk of colorectal cancer (odd ratio (OR) = 1.041, p = 0.035 by fixed-effects inverse variance weighted (IVW) method (IVW_FE), OR = 1.086, p = 0.005 by weighted median; OR = 1.101, p = 0.048 by weighted mode, respectively). According to the weighted median and weighted mode, atorvastatin could modestly decrease the risk of liver cell cancer (OR = 0.989, p = 0.049, and OR = 0.984, p = 0.004, respectively) and head and neck cancer (OR = 0.972, p = 0.020). Besides, rosuvastatin use could reduce the bile duct cancer risk by 5.2% via IVW_EF method (OR = 0.948, p = 0.031). No significant causality was determined in simvastatin use and pan-cancers via the IVW_FE or multiplicative random-effects IVW (IVW_MRE) method if applicable (p > 0.05). There was no horizontal pleiotropy observed in the MR analysis and the leave-one-out analysis proved the stability of the results.

Conclusion: The causalities between statin use and cancer risk were only observed in colorectal …