Source: Nielsen SF. N Engl J Med. 2012;367:1792-1802.
November 09, 2012
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Statin use reduced cancer-related mortality

Source: Nielsen SF. N Engl J Med. 2012;367:1792-1802.
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Results of a study conducted by researchers in Denmark showed statin use was associated with up to a 15% reduction in cancer-related mortality.

The findings demonstrate a need for prospective evaluation of the possibility that statin use prolongs survival of patients with malignancies, researchers said.

Statins inhibit the production of endogenous cholesterol and block protein pre-nylation, which can ultimately influence cancer growth.

Researchers hypothesized that statin use begun before a cancer diagnosis is associated with reduced cancer-related mortality.

Sune F. Nielsen, PhD, of the department of clinical biochemistry at Copenhagen University Hospital in Herlev, Denmark, and colleagues assessed mortality among patients from the entire Danish population who received a diagnosis of cancer between 1995 and 2007.

Follow-up continued until 2009, with a median time of 2.6 years.

The researchers identified 295,925 patients aged at least 40 years. Of them, 18,721 patients used statins regularly prior to their cancer diagnosis and 277,204 had never used statins.

Follow-up equaled 1,072,503 person-years. During that time, 195,594 of the patients died. Of those, 162,067 died from cancer, 14,489 died from cardiovascular causes and 19,038 died from other causes.

“The cumulative incidence of death from any cause as a function of follow-up time from the date of the cancer diagnosis was lower among statin users than among patients who had never used statins,” Nielsen and colleagues wrote.

Multivariable-adjusted HR for death from any cause among statin users vs. patients who never used statins was 0.85 (95% CI, 0.83-0.87). The multivariable-adjusted HR for death from cancer among statin users was 0.85 (95% CI, 0.82-0.87), according to study results.

The reduced cancer-related mortality among statin users as compared with those who had never used statins was observed for 13 cancer types. The multivariable-adjusted HR for death from cancer among statin users ranged from 0.64 (95% CI, 0.46-0.88) for cervical cancer to 0.89 (95% CI, 0.81-0.98) for pancreatic cancer.

For patient death from any cause, researchers measured defined daily doses of statins as 0.01 to 0.75 (HR=0.82; 95% CI, 0.81-0.85), 0.76 to 1.50 (HR=0.87; 95% CI, 0.83-0.89), and more than 1.50 (HR=0.87; 95% CI, 0.81-0.91).

For patient death from cancer, researchers measured defined daily doses of statins as 0.01 to 0.75 (HR=0.83; 95% CI, 0.81-0.86), 0.76 to 1.50 (HR=0.87; 95% CI, 0.83-0.91), and more than 1.50 (HR=0.87; 95% CI, 0.81-0.92).

"Our findings are plausible because statins inhibit cholesterol synthesis within cells through the inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in the mevalonate and cholesterol-synthesis pathway,” Nielsen and colleagues wrote. “Many of these downstream products are used in cell proliferation because they are required for critical cellular functions such as maintenance of membrane integrity, signaling, protein synthesis and cell-cycle progression. Disruptions of these processes in malignant cells result in the inhibition of cancer growth and metastasis.”

In an accompanying editorial, Neil E. Caporaso, MD, senior investigator in the genetic epidemiology branch of the NIH, urged caution in interpreting the findings.

“The authors suggest clinical trials as a next step, but given the questions raised and the need to verify and refine the hypothesis, it would be particularly useful to examine the results of existing statin trials and cohorts beforehand in order to determine the agent, dose and duration of follow-up for an efficient, powerful and convincing study of this important public health question,” Caporaso wrote.