Statins, Low-Density Lipoprotein Cholesterol, and Risk of Cancer

ObjectivesWe sought to assess whether statin-mediated reductions in low-density lipoprotein cholesterol (LDL-C) are associated with an increased risk of cancer.BackgroundWe recently reported an inverse association between on-treatment LDL-C levels and incident cancer in statin-treated patients enrolled in large randomized controlled trials, raising concern that LDL-C lowering by statins may increase cancer risk. However, meta-analyses suggest a neutral overall effect of statins on incident cancer.MethodsA systematic literature search identified 15 eligible randomized controlled trials of statins with ≥1,000 person-years of follow-up that provided on-treatment LDL-C levels and rates of incident cancers (19 statin and 14 control arms, 437,017 person-years cumulative follow-up, and 5,752 incident cancers).ResultsIn the statin arms, meta-regression analysis demonstrated an inverse association between on-treatment LDL-C and incident cancer, with an excess of 2.2 (95% confidence interval: 0.7 to 3.6) cancers per 1,000 person-years for every 10 mg/dl decrement in on-treatment LDL-C (p = 0.006). The corresponding difference among control arms was 1.2 (95% confidence interval: −0.2 to 2.7, p = 0.09). Compared with the control arms, the statin regression line was significantly shifted leftward, such that similar rates of incident cancer were associated with lower on-treatment LDL-C (p < 0.05). Meta-regression demonstrated that statins lack an effect on cancer risk across all levels of on-treatment LDL-C.ConclusionsThere is an inverse association between on-treatment LDL-C and incident cancer. However, statins, despite producing marked reductions in LDL-C, are not associated with an increased risk of cancer.