The statin-low cholesterol-cancer conundrum.
Hundreds of millions of people all over the globe are currently being administered statins because it is believed that their lipid lowering actions provide cardioprotective benefits. Adverse effects are considered uncommon and mild, and authors of numerous case–control studies of patients on statin treatment and matched, untreated individuals have even suggested a protective effect against numerous non-cardiovascular diseases, including cancer. In contrast, four controlled, randomized statin trials have resulted in a statistically significant increase of cancer in the treatment group; and several case–control and cohort studies have also shown a significant risk of cancer associated with statins. To add further confusion to this issue, meta-analyses of controlled, randomized statin trials have shown neither an increased nor a decreased risk of cancer.1 Some of these discrepancies may result from the failure to recognize that the recordings of cancer in statin trials are biased for several reasons.

Several cohort studies of healthy people have shown that low cholesterol is a risk marker for future cancer. The usual interpretation has been that the association is secondary, because in most studies the association disappeared after having excluded early cancer cases. A common explanation has been that preclinical cancers might use cholesterol, which would lead to lower levels. However, when searching Pubmed with the words ‘cancer AND cholesterol’ we identified nine cohort studies including more than 140 000 individuals, where cancer was inversely associated with cholesterol measured 10–30 years earlier, and where the association persisted after exclusion of cancer cases appearing during the first 4 years (Table 1).2–10 It seems unlikely that the liver would be unable to produce the extra cholesterol necessary for early tumor growth, considering that much larger amounts are steadily made for the constant renewal of our cells. Moreover, none of these cohort studies has been corrected …