Statins and the Risk of Colorectal Cancer

Department of Epidemiology, University of Michigan, Ann Arbor 48109-0638, USA.
New England Journal of Medicine (Impact Factor: 55.87). 06/2005; 352(21):2184-92. DOI: 10.1056/NEJMoa043792
Source: PubMed


Statins are inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase and effective lipid-lowering agents. Statins inhibit the growth of colon-cancer cell lines, and secondary analyses of some, but not all, clinical trials suggest that they reduce the risk of colorectal cancer.
The Molecular Epidemiology of Colorectal Cancer study is a population-based case-control study of patients who received a diagnosis of colorectal cancer in northern Israel between 1998 and 2004 and controls matched according to age, sex, clinic, and ethnic group. We used a structured interview to determine the use of statins in the two groups and verified self-reported statin use by examining prescription records in a subgroup of patients for whom prescription records were available.
In analyses including 1953 patients with colorectal cancer and 2015 controls, the use of statins for at least five years (vs. the nonuse of statins) was associated with a significantly reduced relative risk of colorectal cancer (odds ratio, 0.50; 95 percent confidence interval, 0.40 to 0.63). This association remained significant after adjustment for the use or nonuse of aspirin or other nonsteroidal antiinflammatory drugs; the presence or absence of physical activity, hypercholesterolemia, and a family history of colorectal cancer; ethnic group; and level of vegetable consumption (odds ratio, 0.53; 95 percent confidence interval, 0.38 to 0.74). The use of fibric-acid derivatives was not associated with a significantly reduced risk of colorectal cancer (odds ratio, 1.08; 95 percent confidence interval, 0.59 to 2.01). Self-reported statin use was confirmed for 276 of the 286 participants (96.5 percent) who reported using statins and whose records were available.
The use of statins was associated with a 47 percent relative reduction in the risk of colorectal cancer after adjustment for other known risk factors. Because the absolute risk reduction is likely low, further investigation of the overall benefits of statins in preventing colorectal cancer is warranted.

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    • "Risk factors for CRC include advanced age, medical history of benign adenomatous polyps and inflammatory bowel diseases, family history of CRC, low intake of vegetables and fruits and high intake of dietary fat (particularly animal fat) and processed meat [3], [4], [5], [6]. Chronic consumption of non-steroidal anti-inflammatory drugs, hormone replacement therapy and statins are protective [7], [8]. The role of other lifestyle factors such as tobacco smoking [9], [10] or alcohol consumption [11], [12], [13], [14], [15], [16] remains inconclusive. "
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    • "Epidemiological studies, the meta-analyses of statins use, and cancer risk in the general population have provided conflicting results. Some studies have shown cancer risk reduction associated with statins use (16–18) while other studies have reported no effect from its use (19–21) or even an increased risk (22). Unexpectedly, the typical response to simvastatin was greater in poorly-differentiated cells when compared to the well-differentiated cells (23). "
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    • "Clinical data indicate that statin-treated patients have diminished intraplaque angiogenesis [45], which suggests that statins have angiostatic effects in vivo. It is also intriguing that statins have been reported to reduce the growth and spread of many cancers [46, 47], which may be related to inhibition of angiogenesis [48]. The present study also showed that lovastatin cased the abrogation of cell-cell adhesion and degradation of capillary tubes. "
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