Inverse Association between Statin Use and Cancer Mortality Relates to Cholesterol Level

Abstract

Statins have been associated with a decreased cancer mortality. However, cholesterol level as such may modify the risk of cancer death. To clarify the complex interplay between statins, cholesterol level, and cancer mortality, we conducted a comprehensive analysis to separate the effects of cholesterol level and statin medication on cancer mortality. Our study population consisted of 16,924 men participating in the Finnish Randomized Study of Screening for Prostate Cancer with at least one cholesterol measurement during follow-up (1996–2017). Cox proportional regression was used to estimate hazard ratios. In total, 1699 cancer deaths were observed during the median follow-up of 19 years. When statins’ association with the risk of cancer death was estimated without adjustment for cholesterol level, statin use was associated with a lowered cancer mortality (HR 0.87; 95% CI 0.79–0.97) compared to non-users. However, with further adjustment for total cholesterol level, statin use was no longer associated with a lower cancer mortality (HR 1.08; 95% CI 0.97–1.20). Upon stratified analysis, statin use was associated with a decreased cancer mortality only if the total cholesterol level decreased after the initiation of statin use (HR 0.66; 95% CI 0.58–0.76). The inverse association between statin use and cancer mortality is limited to men with a reduction in total cholesterol level after the commencement of statins, i.e., statin use is associated with a lowered cancer mortality only if the total cholesterol level decreases. This suggests that the effect of statin use on cancer mortality relates to the decreased total cholesterol level.

Statin Use, Cholesterol Level, and Mortality Among Females With Breast Cancer

“…Statin, Cholesterol, and Mortality Among Females With BC the serum cholesterol level decreased simultaneously, although the subgroup analyses were limited by low statistical power. This finding suggests that serum cholesterol may be an important factor in BC and that the previously reported 26 inverse association between statin use and BC mortality is likely mediated by underlying cholesterol level changes. Nevertheless, statin use after BC diagnosis was associated with a decreased risk for BC death even after adjustment for cholesterol level.…”

Statin Use and Survival Among Men Receiving Androgen-Ablative Therapies for Advanced Prostate Cancer

“…It is particularly noteworthy that serum cholesterol levels were not adjusted for in any included studies. Serum cholesterol levels appear to correlate with levels of prostate-specific antigen 47 , 48 and may in part drive the statin–prostate cancer association, 49 , 50 potentially contributing to residual confounding of these findings. Second, the retrospective nature of exposure assessment leading to uncaptured discontinuation of or nonadherence to statin therapy may limit the accuracy of the primary outcomes.…”