By Duane Graveline, M.D., M.P.H.
Statins are immunosuppressive drugs. This is why they can even be used in organ transplants. The world had no idea of this potential cancer provoking side effect of statins until the work of Ora Shovman in 2002.
In his paper, "Antiinflammatory and immunomodulatory properties of statins" ( Ref.1 ). he announced to the world that statins inhibit NF-kappaB ( nuclear factor kappa B ) - part of the mevalonate blockade problem of statins.
Since then we have learned that the good that statins do, the diminished cardiovascular risk, seemingly has nothing to do with cholesterol lowering. This benefit is apparently due to the anti-inflammatory action of statins, for atherosclerosis is an inflammatory process. In retrospect, this was a colossal oversight in which everyone was to blame.
More recently we have learned how statins directly damage mitochondria, explaining why neuropathies, myopathies and many cases of ALS-like neuromuscular degeneration are permanent. And now we understand the reality of statin associated cancer.
In the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) trial ( Ref.2 ), a 3.2 year, high-risk 75 year old average age of participant study for cardiovascular disease prevention, cancer incidence was significantly increased in the pravastatin treated group. Among the statin treated patients, the increase in cancer mortality was equal in magnitude to the decrease in cardiovascular disease mortality, leaving total mortality unchanged.
In the Cholesterol and Recurrent Events (CARE) trial ( Ref.3 ) involving the use of Pravachol, Sacks and colleagues reported a statistically significant increase in the incidence of breast cancer among postmenopausal women treated with pravastatin for 4 to 6.2 years when compared with placebo.
In a study titled "Statin use and the risk of breast cancer" ( Ref.4 ), Patricia Beck and co-workers reviewed the Saskatchewan's population health services database for breast cancer occurrence. 13,592 statin users, 55 years of age or older, were compared with 53,880 non-statin users.
879 incident breast cancer cases were identified during the 8.5 years of observation. Background data information included prior use of oral contraceptive and hormone replacement therapy. This study revealed a not quite significant 15 percent increase in breast cancer occurrence among the statin users. They noted no significant correlation with prior use of either oral contraception or hormone replacement therapy.
The authors of this study did observe an unusual correlation of cancer incidence with duration of statin therapy in that the incidence of cancer in short-term statin users was somewhat higher than it was in long term statin users. They did not attempt to explain this observation. I submit that adverse reactions are a very likely cause of statin drug discontinuation. Cognitive dysfunction, subtle emotional and behavioral disorders or mild neuromuscular complaints well could have been the motivation for stopping their new statin medication.
This would give a cohort of former statin users with demonstrated sensitivity to statin use and along with this sensitivity would come susceptibility. Since most side effects are a result of statin associated mevalonate blockade, one can assume this cohort of "statin sensitives" must result in which relative immunodeficiencies exist, reflected by increased incidence of breast cancer.
As Dr. Paul Rosch reported in his Weston Price Foundation presentation of May 2003 it was among the Zocor hyper-responders in Masuzaki's study of the use of Zocor on Japanese patients with hypercholesterolemia that excess deaths from malignancy were observed. Of the 12 cancer deaths reported in this group whose cholesterols plummeted deeply with Zocor use, four were from gastric cancer and two were from lung cancer. This heightened cancer risk may be due to at least partial loss of immuno-resistance secondary to NF-kB inhibition.
Luca Mascitelli and others reported in Dermatology and Endocrinology ( Ref.5 ) with an article titled "The epidemic of nonmelanoma skin cancer and the widespread use of statins. Is there a connection?" The authors hypothesized that this 'epidemic' of non-melanoma skin cancer might be related to the widespread use of statin drugs.
They reported that "The incidence of nonmelanoma skin cancer ( NMSC ) in the United States has substantially increased from 1992 through 2006 with a 4.2% yearly average increase of cases." They also observed that "An emerging important risk factor for nonmelanoma skin cancers is immunosuppression, which can justify the increased prevalence of these tumors in the elderly who are relatively immunosuppressed." The authors also stated that "Immunosuppressive treatments seem to act as a catalyst for skin carcinogenesis as they increase the frequency, number and aggressiveness of such tumors."
Of great interest to cancer researchers is that one of the means by which statins suppress the immune system is by increasing the numbers and functionality of certain of the blood lymphocytes known as regulatory T cells (Tregs). An increase in Treg numbers and functionality impairs the host anti-tumor responses. Research has found that the higher the Treg cell count, the lower patient survival is. The elderly may be more susceptible to the immunosuppressive effects of statins since they are more likely to harbor occult tumor cells.
But the most persuasive idea for statins' contribution to cancer comes from Shovman's original paper in 2002 - Antiinflammatory and immunomodulatory properties of statins - ( Ref.1 ) when he revealed that the primary mechanism of action of statins was the inhibition of nuclear factor kappa B, a transcriptase influencing our entire inflammatory and immunodefense system.
Ref 1. http://www.ncbi.nlm.nih.gov/pubmed/12018465
Ref 2. http://www.medscape.com/viewarticle/444971
Ref 3. http://www.nejm.org/doi/full/10.1056/NEJM199610033351401#t=articleResults
Ref 4. http://www.jclinepi.com/article/S0895-4356(02)00614-5/abstract
Ref 5. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084964/
Duane Graveline MD MPH
Former USAF Flight Surgeon
Former NASA Astronaut
Retired Family Doctor
Updated July 2011