For Patients with Colorectal Cancer, the Long-Term Use of Statins Is Associated with Better Clinical Outcomes
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Statins have been found to suppress tumor cell growth and to limit the ability of tumor cells to metastasize in studies involving cell lines and animals. To explore how the long-term use of statins influences the presentation and survival of patients with colorectal cancer (CRC), we conducted a retrospective case-control study of male patients with a new diagnosis of CRC who we categorized as: (1) Statin Users who used statins continuously ≥3 years prior to the diagnosis of CRC and (2) Statin Non-Users who did not use statins. Clinical factors were analyzed by simple Chi-square and multivariate regression analysis to identify independent predictors for advanced CRC. We identified 1,309 male patients with a new diagnosis of CRC (mean age 69 ± 1.1 (SE) years; 326 Statin Users, 983 Statin Non-Users). Compared to Statin Non-Users, Statin Users had a less advanced tumor stage (2.2 vs. 2.6; P < 0.01), a lower prevalence of metastases (OR = 0.7 [0.4–0.9, 95% CI]; P < 0.01), and a higher frequency of right-sided tumors (OR = 1.6 [1.3–2.1], 95%CI]; P < 0.01). Overall 5-year survival for Statin Users was 37% compared to 33% in Statin Non-Users (OR = 0.7 [0.6–0.9], 95%CI]; P = 0.03). In patients who present to the hospital with CRC, the long-term use of statins is associated with a less advanced tumor stage, a higher prevalence of right-sided tumors, a lower frequency of distant metastases, and a better survival rate.
- Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2008. CA Cancer J Clin. 2008;58:71–96. doi:10.3322/CA.2007.0010. CrossRef
- Wong WW, Dimitroulakos J, Minden MD, Penn LZ. HMG-CoA reductase inhibitors and the malignant cell: the statin family of drugs as triggers of tumor-specific apoptosis. Leukemia. 2002;16:508–519. doi:10.1038/sj.leu.2402476. CrossRef
- Jakobisiak M, Golab J. Potential antitumor effects of statins. Int J Oncol. 2003;23:1055–1069. Review.
- Carlberg M, Dricu A, Blegen H, et al. Mevalonic acid is limiting for N-linked glycosylation and translocation of the insulin-like growth factor-1 receptor to the cell surface. Evidence for a new link between 3-hydroxy-3-methylglutaryl-coenzyme a reductase and cell growth. J Biol Chem. 1996;271:17453–17462. doi:10.1074/jbc.271.29.17453. CrossRef
- Narisawa T, Morotomi M, Fukaura Y, Hasebe M, Ito M, Aizawa R. Chemoprevention by pravastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, of N-methyl-N-nitrosourea-induced colon carcinogenesis in F344 rats. Jpn J Cancer Res. 1996;87:798–804.
- Agarwal B, Rao CV, Bhendwal S, et al. Lovastatin augments sulindac-induced apoptosis in colon cancer cells and potentiates chemopreventive effects of sulindac. Gastroenterology. 1999;117:838–847. doi:10.1016/S0016-5085(99)70342-2. CrossRef
- Poynter JN, Gruber SB, Higgins PD, et al. Statins and the risk of colorectal cancer. N Engl J Med. 2005;352:2184–2192. doi:10.1056/NEJMoa043792. CrossRef
- Kusama T, Mukai M, Iwasaki T, et al. Inhibition of epidermal growth factor-induced RhoA translocation and invasion of human pancreatic cancer cells by 3-hydroxy-3-methylglutaryl-coenzyme a reductase inhibitors. Cancer Res. 2001;61:4885–4891.
- Zielinski SL. Following positive epidemiologic studies, statins to enter clinical trials for cancer prevention. J Natl Cancer Inst. 2005;97:1172–1173.
- Bhuket TP, Higgins PD. Drug insight: statins and gastrointestinal cancer. Nat Clin Pract Gastroenterol Hepatol. 2006;3:552–562. doi:10.1038/ncpgasthep0603. CrossRef
- Wang IK, Lin-Shiau SY, Lin JK. Suppression of invasion and MMP-9 expression in NIH 3T3 and v-H-Ras 3T3 fibroblasts by lovastatin through inhibition of ras isoprenylation. Oncology. 2000;59:245–254. doi:10.1159/000012168. CrossRef
- Park HJ, Kong D, Iruela-Arispe L, Begley U, Tang D, Galper JB. 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors interfere with angiogenesis by inhibiting the geranylgeranylation of RhoA. Circ Res. 2002;91:143–150. doi:10.1161/01.RES.0000028149.15986.4C. CrossRef
- Hindler K, Cleeland CS, Rivera E, Collard CD. The role of statins in cancer therapy. Oncologist. 2006;11:306–315. doi:10.1634/theoncologist.11-3-306. CrossRef
- Broitman SA, Wilkinson J, Cerda S, Branch SK. Effects of monoterpenes and mevinolin on murine colon tumor CT-26 in vitro and its hepatic “metastases” in vivo. Adv Exp Med Biol. 1996;401:111–130.
- Swamy MV, Cooma I, Reddy BS, Rao CV. Lamin B caspase-3 activity, and apoptosis induction by a combination of HMG-CoA reductase inhibitor and COX-2 inhibitors: a novel approach in developing effective chemopreventive regimens. Int J Oncol. 2002;20:753–759.
- Coogan PF, Smith J, Rosenberg L. Statin use and risk of colorectal cancer. J Natl Cancer Inst. 2007;99:32–40. CrossRef
- Bonovas S, Filioussi K, Flordellis CS, Sitaras NM. Statins and the risk of colorectal cancer: a meta-analysis of 18 studies involving more than 1.5 million patients. J Clin Oncol. 2007;25:3462–3468. doi:10.1200/JCO.2007.10.8936. CrossRef
- Kaye JA, Jick H. Statin use and cancer risk in the general practice research database. Br J Cancer. 2004;90:635–637. doi:10.1038/sj.bjc.6601566. CrossRef
- Graaf MR, Beiderbeck AB, Egberts AC, Richel DJ, Guchelaar HJ. The risk of cancer in users of statins. J Clin Oncol. 2004;22:2388–2394. doi:10.1200/JCO.2004.02.027. CrossRef
- For Patients with Colorectal Cancer, the Long-Term Use of Statins Is Associated with Better Clinical Outcomes
Digestive Diseases and Sciences
Volume 54, Issue 6 , pp 1307-1311
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- Colorectal cancer
- 3-Hydroxy-3-methyl glutaryl coenzyme A inhibitors
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- Author Affiliations
- 1. Dallas Veteran’s Affairs Medical Center, Departments of Internal Medicine, 4500 S. Lancaster Road (111B1), Dallas, TX, 75216, USA
- 2. University of Texas Southwestern Medical School, Dallas, TX, USA
- 3. Dallas Veterans Affairs Research Corporation, Dallas, TX, USA