Our aim was to use MR to appraise the causal nature and mechanistic basis of the relationship between cholesterol-lowering and risk of oral and oropharyngeal cancer by investigating germline variation in HMGCR, NPC1L1, CETP, PCSK9 and LDLR, and other related lipid traits such as circulating LDL-C. Here, NPC1L1 is linked to oropharynx cancer.