November 7th, 2012
Statins Use Linked to Reduction in Cancer Mortality
Larry Husten, PHD
A large new study raises the possibility that statin use may lead to a decline in cancer mortality. Researchers in Denmark used health data from the entire population of the country and analyzed the information from nearly 300,000 patients who were diagnosed with cancer between 1995 and 2007. The authors note that the relationship is biologically plausible, since cholesterol synthesis is required for cell proliferation and other critical cellular functions.
In their paper, published in the New England Journal of Medicine, the researchers compared 18,721 cancer patients who were statin users prior to their diagnosis with 277,204 who had never used statins. Here are the adjusted hazard ratios for statin users:
- All-cause mortality: 0.85 (0.83-0.87)
- Death from cancer: 0.85 (0.82-0.87)
A similar and consistent pattern was noted for different types of cancer, although these differences did not always achieve statistical significance. No dose-response relationship was observed in the study.
In an accompanying editorial, Neil Caporaso notes that despite the considerable strengths of the study, which used data from the entire country of Denmark, the researchers were nevertheless unable to account for residual confouding differences between statin users and nonusers. The “consistent and substantial declines in mortality across diverse cancers” need to be interpreted with caution, he wrote. Caporaso suggests a variety of different research directions for further study of the important question of the relationship between statins and cancer.
This study is another observational study, that likley is all just confounding. This question has been asked and answered – in CTT, with 5 year follow-up: Lack of Effect of Lowering LDL Cholesterol on Cancer:
Meta-Analysis of Individual Data from 175,000 People in
27 Randomised Trials of Statin Therapy PLoS ONE 7(1): e29849
“Individual records of 134,537 participants in 22 randomised trials of statin versus control (median
duration 4.8 years) and 39,612 participants in 5 trials of more intensive versus less intensive statin therapy (median duration
5.1 years) were obtained. Reducing LDL-C with a statin for about 5 years had no effect on newly diagnosed cancer or on
death from such cancers in either the trials of statin versus control (cancer incidence: 3755 [1.4% per year [py]] versus 3738
[1.4% py], RR 1.00 [95% CI 0.96-1.05]; cancer mortality: 1365 [0.5% py] versus 1358 [0.5% py], RR 1.00 [95% CI 0.93–1.08]) or
in the trials of more versus less statin (cancer incidence: 1466 [1.6% py] vs 1472 [1.6% py], RR 1.00 [95% CI 0.93–1.07]; cancer
mortality: 447 [0.5% py] versus 481 [0.5% py], RR 0.93 [95% CI 0.82–1.06]).”
and with 11 years follow-up in HPS: Effects on 11-year mortality and morbidity of lowering LDL cholesterol with simvastatin for about 5 years in 20 536 high-risk individuals: a randomised controlled trial
http://www.thelancet.com Published online November 23, 2011
“During the combined in-trial and post-trial periods, no
significant differences were recorded in cancer incidence at all sites (0·98 [0·92–1·05]) or any particular site, or in
mortality attributed to cancer (1·01 [0·92–1·11])”
How many times do we need to learn that observational studies give the wrong answer on treatment effects?
It may in fact be the opposite, as we have suggested in a recent paper: statin treatment, or rather low cholesterol may predispose to cancer (1). For instance, in the two first simvastatin trials 4S and HPS the number of non-melanoma skin cancer was greater in the treatment groups and with statistical significance, if the results from both trials are calculated together. The reason why meta-analyses of the statin trials do not show neither benefit or harm may be because after the publication of HPS, no trial report has published the number of non-melanoma skin cancers.
I assume that the reason for not reporting it is that non-melanoma skin cancer is seen as an innocent disease. However, if low cholesterol or statin treatment is carcinogenic, the first cancer type we should expect to see is non-melanoma skin cancer, because it is very easy to discover at an early stage.
The explanation may be that the lipoproteins partake in the immune defense system by binding and inactivating all kinds of bacteria and virus (2), and about 20 % of all cancers are caused by microorganisms.
1. Ravnskov U, McCully KS, Rosch PJ. The statin-low cholesterol-cancer conundrum. QJM 2012;105:383-8.
2. Ravnskov U, McCully KS. Vulnerable plaque formation from obstruction of vasa vasorum by homocysteinylated and oxidized lipoprotein aggregates complexed with microbial remnants and LDL autoantibodies. Ann Clin Lab Sci 2009;39:3-16
Chris Cannon makes a compelling counter to this observational trial.
I think that this trial demonstrates that use of statin correlates with compliant subjects. Compliant subjects are more likely to participate in cancer therapy and therefore a reduction in mortality.