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    Statins Do Not Protect Against Cancer: Quite the Opposite

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    graham64
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    Statins Do Not Protect Against Cancer: Quite the Opposite

    Post by graham64 on Mon Jun 15 2015, 23:03

    2015 by American Society of Clinical Oncology

    In their cohort study of statin-treated patients and nontreated controls, Cardwell et al1 concluded that statin treatment may prevent colorectal cancer. However, there are significant flaws in their study.

    At least nine studies have shown that cancer is associated with low cholesterol, measured 10 to > 30 years before diagnosis.2 Because most patients receiving statin treatment have lived most of their lives with high cholesterol, risk for cancer mortality might have been lower even without statin treatment compared with the untreated cohort with normal or low cholesterol. A similar study by Nielsen et al3 supports this interpretation, because mortality was lowest among those who were treated with the lowest statin dose. Furthermore, adherence to statins is low, particularly when prescribed for primary prevention. In a Canadian study including > 85,000 patients, 75% had stopped the treatment at 2-year follow-up.4

    To claim that statin treatment protects against cancer is therefore impossible with the method used by Caldwell et al.1 Instead, cancer mortality should be related to the achieved lipid values, as reported by Matsuzaki et al,5 who administered simvastatin 5 to 10 mg per day to > 47,000 patients. After 6 years, cancer mortality was 3× higher in patients whose total cholesterol was < 160 mg/dL compared with those whose cholesterol was normal or high (P < .001).

    In fact, evidence that statin treatment may cause cancer is much stronger.2 Several cholesterol-lowering drugs, including statins, have been found to be carcinogenic in rodents in doses that produce blood concentrations of the drugs similar to those attained in treating patients.2 In accordance, breast cancer occurred in 12 of 286 women in the treatment group of the CARE (Cholesterol and Recurrent Events) trial, but only in one of 290 in the placebo group (P = .002). In the PROSPER (Prospective Study of Pravastatin in the Elderly at Risk) trial, cancer occurred in 245 of 2,891 patients in the treatment group, but only in 199 of 2,913 in the placebo group (P = .02). In the SEAS (Simvastatin and Ezetimibe in Aortic Stenosis) trial, cancer occurred in 39 of 944 patients in the treatment group, but only in 23 of 929 in the placebo group (P < .05).2 In the two first simvastatin trials, nonmelanoma skin cancer was seen more often as well, and with statistical significance if the results are calculated together (256 of 12,454 v 208 of 12,459; P = .028).2 The latter finding may explain the current so-called epidemic of nonmelanoma skin cancer.6

    Several case-control studies have also shown that patients with cancer have been treated with statins significantly more frequently than controls without cancer matched for age and sex.2 Furthermore, a recent study showed that 10 years of statin therapy increased women's risk of invasive ductal carcinoma by 83% and their risk of invasive lobular carcinoma of the breast by 97%.7

    An apparent contradiction is that meta-analyses of the statin trials have found no increase of cancer. However, since the publication of the HPS (Heart Protection Study) trial,6 the number of nonmelanoma skin cancers—the easiest malignancies to detect early—has not been reported in any trial. Furthermore, it may take 10 to 20 years before exposure to carcinogenic chemicals results in cancer. Bronchial cancer, for instance, does not appear until after 10 years of smoking, and the length of almost all the statin trials has only been 5 years at most.

    As noted, it may be that statins per se are not carcinogenic but rather that this adverse effect results from their ability to lower blood lipids. More than a dozen research groups have documented that lipoproteins, particularly LDL, partake in the immune system by binding and inactivating all kinds of microorganisms and their toxic products.8,9 Because certain microorganisms have been incriminated as a possible cause of different malignancies, including colorectal cancer,10 it is difficult to understand how lowering LDL cholesterol could prevent cancer.

    Association never proves causation. Although it may be difficult to prove that statins can cause or prevent cancer, the preponderance of evidence favors the former.

    http://m.jco.ascopubs.org/content/early/2015/01/20/JCO.2014.58.9564.full



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