PurposeThe　aim　of　this　study　was　to　investigate　the　causal　relationship　between　low-density　lipoprotein　cholesterol　(LDL-C)　and　five　cancers　(breast,　cervical,　thyroid,　prostate　and　colorectal)　using　the　Mendelian　Randomization　(MR)　method,　with　a　view　to　revealing　the　potential　role　of　LDL-C　in　the　development　of　these　cancers.MethodsWe　used　gene　variant　data　and　disease　data　from　the　Genome-Wide　Association　Study　(GWAS)　database　to　assess　the　causal　relationship　between　LDL-C　and　each　cancer　by　Mendelian　randomisation　analysis　methods　such　as　inverse　variance　weighting　and　MR-Egger.　Specifically,　we　selected　Proprotein　convertase　subtilisin/kexin　type　9　(PCSK9)　and　3-hydroxy-3-methylglutaryl-CoA　reductase　(HMGCR),　genes　associated　with　LDL-C　levels,　as　instrumental　variables,　extracted　the　corresponding　single　nucleotide　polymorphism　(SNP)　data　and　analysed　the　associations　of　these　SNPs　with　five　cancers.In　addition,　sensitivity　analyses　and　heterogeneity　tests　were　performed　to　ensure　the　reliability　of　the　results.ResultsThe　analyses　showed　that　when　using　HMGCR　gene,　LDL-C　were　significantly　and　positively　associated　with　breast　(OR:1.200,　95%　CI:1.082-1.329,　p　=　0.001),　prostate　(OR:1.198,　95%　CI:1.050-1.366,　p　=　0.007),　and　thyroid　cancers　(OR:8.291,　95%　CI:3.189-　21.555,　p　=　0.00001)　were　significantly　positively　correlated,　whereas　they　were　significantly　negatively　correlated　with　colorectal　cancer　(OR:0.641,　95%　CI:0.442-0.928,　p　=　0.019);　the　results　for　cervical　cancer　were　not　significant　(p　=　0.050).　When　using　the　PCSK9　gene,　LDL-C　levels　were　significantly　and　positively　associated　with　breast　(OR:1.107,　95%:CI　1.031-1.187,　p　=　0.005)　and　prostate　(OR:1.219,　95%:CI　1.101-1.349,　p　=　0.0001)　cancers,　but　not　with　cervical　(p　=　0.294),　thyroid　cancer　(p　=　0.759)　and　colorectal　cancer　(　p　=　0.572).ConclusionAnalyses　using　both　the　HMGCR　and　PCSK9　genes　have　shown　that　LDL-C　may　be　a　potential　risk　factor　for　breast　and　prostate　cancer,　while　analyses　of　the　HMGCR　gene　have　also　suggested　that　LDL-C　may　increase　the　risk　of　thyroid　cancer　and　decrease　the　risk　of　colorectal　cancer.