Statins and Cancer
Do statins protect against cancer?
Can statins cause cancer?
The answer to the first question appears to be "yes" and to the second question is "no", according to research studies.
The scientific evidence is weak in either direction on this question, and if statins do affect cancer risk, the magnitude is small.
In laboratory conditions, statins certainly exhibit antitumor activities in addition to anti-inflammatory ones. Studies have shown that statins can inhibit malignant cell growth and promote apoptosis (cell death important in stopping cancer.) That doesn't necessarily mean they can help prevent or stop cancer in people, though. Sometimes in medical research in vitro and in vivo effects are not identical.
Several large randomized controlled trials of monotherapy for five years show no change in the overall rates of cancer when statins are used regularly. A study of military veterans , however, showed that statin use was associated with lower cancer rates in older men. (The participants in the study were mostly men and the average age was over 65.) There is also evidence, although not conclusive, that statins have a chemopreventative effect on melanoma in younger people. A Finnish study found that men who take statins have lower rates of prostate cancer.
A recent European study of people who already had cancer and took statins found they had significantly lower risk of mortaility from the cancer. This was a very large study of 300,000 patients. People who were using statins at the time of their cancer diagnosis were 15% less likely to die from their cancer. This large study found positive correlation between statin use and survival in 13 types of cancer. Another 14 types of cancer showed no significant change in mortality connected with statin use. The dosage of the statin medications did not appear to have any effect on the correlation.
As far as actually causing cancer, the average duration of the trials was five years, while patients taking stains would take the drugs for longer periods, probably the rest of their lives. Cancers can occur after long latency periods after the person is exposed to the cause of the disease, so you never really know. As time goes by and we get long term data from the millions of people who use stating drugs, epidemiologists will be able to make an even more sure call on this question.
Some scientists feel statins may lower the risk of cancer just by reducing serum cholesterol levels. Another theory is that statins reduce the tendency of a cancer to metastasize. Support for this theory comes from a meta-study that found lower LDL-C levels are associated with higher cancer rates. Cholesterol is known to be needed for cell growth, but it is not thought that the effects of statins on serum cholesterol levels directly affect the development or growth of cancerous tumors. "Statins increase the number of regulatory T cells" but may consquently "impair both the innate4 and adaptive5 host antitumour immune responses." This might pose a problem especially in the elderly who are more likely to harbor "occult" microtumors. Suppress the immune system and they are more likely to get cancer.
Studies published in May 2008 found that incidences of cancer are dramatically reduced when patients take statins in high doses. A University of Michigan study found that regular statin usage was associated with lower risk of colon cancer.
An April 2008 report of Rutgers University research showed that a combination of atorvastatin (Lipitor) and celecoxib (Celebrex) may stop or slow the growth of prostate cancer. Another study announced in 2013 found lower incidences of prostate cancer in patients on statins. This is certainly a pleiotropic effect and nobody is suggesting statins be prescribed to prevent cancer. (The 2013 study found initial incidence of prostate cancer was lowered, but rates of recurrence or progression were unaffected.)
Large scale studies by the Department of Veteran Affairs show statin usage is associated with reduction in rates of lung cancer. And also appear to reduce the risk of pancreatic cancer. A further Baylor College of Medicine published in 2009 showed evidence that statins may prevent or slow liver cancer. An Israeli study released in 2012 found people who took statins were less likely to develop cancer, and the effect was especially pronounced in men and leukemia. A retrospective stufy of over 40000 men concluded statin usage cut risk of prostate cancer by 24 percent.
Researchers in Switzerland and California may have started to uncover the mechanism for chemoprevention. The growth of lymphatic vessels facilitates the growth of tumors and aids in the body's rejection of transplanted organs. Statins appear to inhibit this vessel growth.
The mechanism for any chemoprevenatitive properties are unknown, but the antioxidant properties may provide a clue. Oxidative stress inside the body contributes to growth of plaques in the blood vessel. Oxidative stress is also bad for the heart. Like the phytochemicals in fruits and vegetables, statins are "antioxidants" - they react with the oxidizing agents so those agents don't damage cells. Just as statins are competitive inhibitors of HMG-CoA reductase in the liver (to slow the production of cholesterol), so they compete for oxidating agents. And by reducing the circulation of oxidized LDLs, statins inhibit the uptake of LDLs by macrophages.
Statins inhibit oxidant enzymes like reduced nicotinamide adenine dinucleotide phosphate (NAD[P]H) oxidase and myeloperoxidase. They reduce endothelial dysfunction mainly by their ability to enhance endothelial nitric oxide bioavailability, which is achieved by several mechanisms. The antioxidant properties of statins extend to organ protection especially the myocardium and the lungs.
A meta-analysis of various studies concluded that when patients take statins for cholesterol issue, it has the added benefit of reducing risk for liver cancer substantially. People who took statins for years had over 30% lower risk of developing hepatocellular carcinoma. This reduction was across both sexes and different ages. The reduction was found to be more prevalent in Asian populations than Western ones.
The magnitude of the risk reduction was found to be large, so even though there is a margin for error the results are likely to hold up. A scientists at M.D. Anderson Cancer Center was quoted as calling for a large prospective study to validate the results, Studies have also found statin users are less likely to have liver cirrhosis and the liver disease hepatitis.
A Danish study found statin usage may reduce the risk of the type of brain and nervous system cancer called gliomas when the statins were used in the long term. This is an example of a pleotropic effect of statins. However, another study found a "borderline increased risk" of glioma formation was associated with statin use.
Statins may find some use in immunosuppression following transplants in cancer patients.
An overview discussion of statins and cancer in the Journal of Current Oncology.
From 2020 AACR Meeting: Study shows 40 percent reduction in ovarian cancer mortality in women who use statins.
Lab research suggests statins may reduce the recurrence of breast cancer in women who have had that disease. Breast cancer patients are usually treated to reduce estrogen levels in their bodies, but sometimes the residual cancer cells use cholesterol to produce a biochemical called 25-HC which acts like estrogen to promote tumor growth.
Scientists have also found that over-activation of some genes linked to cholesterol production is associated with more drug-resistant cancer.
https://www.theguardian.com/society/2016/jun/01/statins-breast-cancer-research-treatment-cholesterol-oestrogen Can reducing cholesterol levels with statins make the tumors more amenable to chemotherapy treatment? It’s too early to say, but the research suggests this possibility.