open access

Vol 66, No 4 (2016)
Review paper
Published online: 2016-12-23
Get Citation

Statins and colorectal cancer

Katarzyna Walkiewicz, Michał Walczak, Angelika Copija, Henryk Augustyniak, Teresa Kokot, Małgorzata Muc-Wierzgoń, Ewa Nowakowska-Zajdel
DOI: 10.5603/NJO.2016.0060
·
Nowotwory. Journal of Oncology 2016;66(4):317-321.

open access

Vol 66, No 4 (2016)
Review article
Published online: 2016-12-23

Abstract

Statins are naturally occurring compounds that inhibit the enzyme 3-hydroxy-3-methyl-glutaryl-CoA reductase. Through their beneficial management of the body’s lipid metabolism, they are widely used medicinal drugs employed extensively in the primary and secondary prevention of cardiovascular disease. In addition, many studies to date have shown the therapeutic advantages derived from using statins in conditions such as endometriosis, osteoporosis, polycystic ovary syndrome and rheumatic disease. Due to the steady increase of cancer morbidity rates, as demonstrated by epidemiological data, the putative role of statins in treating or preventing cancer has been ever more frequently investigated; including for colorectal cancer. This paper attempts to bring together current knowledge/ evidence on statin therapy targeted at the development, disease course and treatment of colorectal cancer, both in terms of epidemiological findings and clinical observations. Because of the reported link between metabolic disorders and the development of colorectal cancer, particular focus is given to the effects of statins on signalling pathways involving insulin-like growth factors (IGFs).

Abstract

Statins are naturally occurring compounds that inhibit the enzyme 3-hydroxy-3-methyl-glutaryl-CoA reductase. Through their beneficial management of the body’s lipid metabolism, they are widely used medicinal drugs employed extensively in the primary and secondary prevention of cardiovascular disease. In addition, many studies to date have shown the therapeutic advantages derived from using statins in conditions such as endometriosis, osteoporosis, polycystic ovary syndrome and rheumatic disease. Due to the steady increase of cancer morbidity rates, as demonstrated by epidemiological data, the putative role of statins in treating or preventing cancer has been ever more frequently investigated; including for colorectal cancer. This paper attempts to bring together current knowledge/ evidence on statin therapy targeted at the development, disease course and treatment of colorectal cancer, both in terms of epidemiological findings and clinical observations. Because of the reported link between metabolic disorders and the development of colorectal cancer, particular focus is given to the effects of statins on signalling pathways involving insulin-like growth factors (IGFs).

Get Citation

Keywords

statins, pleiotropic effects of statins, colorectal cancer, epidemiology

About this article
Title

Statins and colorectal cancer

Journal

Nowotwory. Journal of Oncology

Issue

Vol 66, No 4 (2016)

Article type

Review paper

Pages

317-321

Published online

2016-12-23

DOI

10.5603/NJO.2016.0060

Bibliographic record

Nowotwory. Journal of Oncology 2016;66(4):317-321.

Keywords

statins
pleiotropic effects of statins
colorectal cancer
epidemiology

Authors

Katarzyna Walkiewicz
Michał Walczak
Angelika Copija
Henryk Augustyniak
Teresa Kokot
Małgorzata Muc-Wierzgoń
Ewa Nowakowska-Zajdel

References (43)
  1. Gąsior M, Czekaj AD, Przybylska K, et al. Plejotropowe działanie statyn. Choroby Serca i Naczyń. 2008; 5: 141–146.
  2. Endo A, Hasumi K, Negishi S. Monacolins J and L, new inhibitors of cholesterol biosynthesis produced by Monascus ruber. J Antibiot (Tokyo). 1985; 38(3): 420–422.
  3. Alberts AW. Discovery, biochemistry and biology of lovastatin. Am J Cardiol. 1988; 62(15): 10J–15J.
  4. Laws PE, Spark JI, Cowled PA, et al. The role of statins in vascular disease. Eur J Vasc Endovasc Surg. 2004; 27(1): 6–16.
  5. Thurnher M, Nussbaumer O, Gruenbacher G. Novel aspects of mevalonate pathway inhibitors as antitumor agents. Clin Cancer Res. 2012; 18(13): 3524–3531.
  6. Wong WWL, Dimitroulakos J, Minden MD, et al. HMG-CoA reductase inhibitors and the malignant cell: the statin family of drugs as triggers of tumor-specific apoptosis. Leukemia. 2002; 16(4): 508–519.
  7. Gruenbacher G, Gander H, Nussbaumer O, et al. IL-2 costimulation enables statin-mediated activation of human NK cells, preferentially through a mechanism involving CD56+ dendritic cells. Cancer Res. 2010; 70(23): 9611–9620.
  8. Sadeghi MM, Collinge M, Pardi R, et al. Simvastatin modulates cytokine-mediated endothelial cell adhesion molecule induction: involvement of an inhibitory G protein. J Immunol. 2000; 165(5): 2712–2718.
  9. Sławińska A, Kandefer-Szerszeń M. Właściwości przeciwnowotworowe statyn. Postępy Hig Med Dośw. 2008; 62: 393–404.
  10. Krajowy Rejestr Nowotworów (KRN, National Cancer Registry). http://onkologia.org.pl (12.2015).
  11. Arnaud C, Braunersreuther V, Mach F. Toward immunomodulatory and anti-inflammatory properties of statins. Trends Cardiovasc Med. 2005; 15(6): 202–206.
  12. Katz MS, Minsky BD, Saltz LB, et al. Association of statin use with a pathologic complete response to neoadjuvant chemoradiation for rectal cancer. Int J Radiat Oncol Biol Phys. 2005; 62(5): 1363–1370.
  13. Kodach LL, Bleuming SA, Peppelenbosch MP, et al. The effect of statins in colorectal cancer is mediated through the bone morphogenetic protein pathway. Gastroenterology. 2007; 133(4): 1272–1281.
  14. Poynter JN, Gruber SB, Higgins PDR, et al. Statins and the risk of colorectal cancer. N Engl J Med. 2005; 352(21): 2184–2192.
  15. Lipkin SM, Chao EC, Moreno V, et al. Genetic variation in 3-hydroxy-3-methylglutaryl CoA reductase modifies the chemopreventive activity of statins for colorectal cancer. Cancer Prev Res (Phila). 2010; 3(5): 597–603.
  16. Jacobs EJ, Newton CC, Thun MJ, et al. Long-term use of cholesterol-lowering drugs and cancer incidence in a large United States cohort. Cancer Res. 2011; 71(5): 1763–1771.
  17. Broughton T, Sington J, Beales ILP. Statin use is associated with a reduced incidence of colorectal cancer: a colonoscopy-controlled case-control study. BMC Gastroenterol. 2012; 12: 36.
  18. Nielsen SF, Nordestgaard BG, Bojesen SE, et al. Statin use and reduced cancer-related mortality. N Engl J Med. 2012; 367(19): 1792–1802.
  19. Lakha F, Theodoratou E, Farrington SM, et al. Statin use and association with colorectal cancer survival and risk: case control study with prescription data linkage. BMC Cancer. 2012; 12: 487.
  20. Cardwell CR, Hicks BM, Hughes C, et al. Statin use after colorectal cancer diagnosis and survival: a population-based cohort study. J Clin Oncol. 2014; 32(28): 3177–3183.
  21. Şendur MA, Aksoy S, Yalçın B. Do statins really improve colorectal cancer-specific mortality? J Clin Oncol. 2015; 33(7): 811.
  22. Liu Y, Tang W, Wang J, et al. Association between statin use and colorectal cancer risk: a meta-analysis of 42 studies. Cancer Causes Control. 2014; 25(2): 237–249.
  23. Bonovas S, Filioussi K, Flordellis CS, et al. 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(23): 3462–3468.
  24. Boudreau DM, Yu O, Johnson J. Statin use and cancer risk: a comprehensive review. Expert Opin Drug Saf. 2010; 9(4): 603–621.
  25. Shadman M, Newcomb PA, Hampton JM, et al. Non-steroidal anti-inflammatory drugs and statins in relation to colorectal cancer risk. World J Gastroenterol. 2009; 15(19): 2336–2339.
  26. Desai P, Chlebowski R, Cauley JA, et al. Prospective analysis of association between use of statins or other lipid-lowering agents and colorectal cancer risk. Ann Epidemiol. 2012; 22(1): 17–27.
  27. Morris TJ, Palm SL, Furcht LT, et al. The effect of lovastatin on [3H]thymidine uptake in HTC-4 and LLC-L1 tumor cells. J Surg Res. 1996; 61(2): 367–372.
  28. Wong WWL, Dimitroulakos J, Minden MD, et al. HMG-CoA reductase inhibitors and the malignant cell: the statin family of drugs as triggers of tumor-specific apoptosis. Leukemia. 2002; 16(4): 508–519.
  29. Lamprecht J, Wójcik C, Jakóbisiak M, et al. Lovastatin induces mitotic abnormalities in various cell lines. Cell Biol Int. 1999; 23(1): 51–60.
  30. Kim JS, Pirnia F, Choi YH, et al. Lovastatin induces apoptosis in a primitive neuroectodermal tumor cell line in association with RB down-regulation and loss of the G1 checkpoint. Oncogene. 2000; 19(52): 6082–6090.
  31. Al-Haidari AA, Syk I, Thorlacius H. HMG-CoA reductase regulates CCL17-induced colon cancer cell migration via geranylgeranylation and RhoA activation. Biochem Biophys Res Commun. 2014; 446(1): 68–72.
  32. McCarty MF. Suppression of dolichol synthesis with isoprenoids and statins may potentiate the cancer-retardant efficacy of IGF-I down-regulation. Med Hypotheses. 2001; 56(1): 12–16.
  33. McCarty MF. Current prospects for controlling cancer growth with non-cytotoxic agents--nutrients, phytochemicals, herbal extracts, and available drugs. Med Hypotheses. 2001; 56(2): 137–154.
  34. Walkiewicz K, Gętek M, Muc-Wierzgoń M, et al. [The importance of ADAM family proteins in malignant tumors]. Postepy Hig Med Dosw (Online). 2016; 70: 67–73.
  35. Luan Z, Chase AJ, Newby AC. Statins inhibit secretion of metalloproteinases-1, -2, -3, and -9 from vascular smooth muscle cells and macrophages. Arterioscler Thromb Vasc Biol. 2003; 23(5): 769–775.
  36. Vincent L, Chen W, Hong L, et al. Inhibition of endothelial cell migration by cerivastatin, an HMG-CoA reductase inhibitor: contribution to its anti-angiogenic effect. FEBS Lett. 2001; 495(3): 159–166.
  37. Bellosta S, Via D, Canavesi M, et al. HMG-CoA reductase inhibitors reduce MMP-9 secretion by macrophages. Arterioscler Thromb Vasc Biol. 1998; 18(11): 1671–1678.
  38. Arnaud C, Braunersreuther V, Mach F. Toward immunomodulatory and anti-inflammatory properties of statins. Trends Cardiovasc Med. 2005; 15(6): 202–206.
  39. Chapman-Shimshoni D, Yuklea M, Radnay J, et al. Simvastatin induces apoptosis of B-CLL cells by activation of mitochondrial caspase 9. Exp Hematol. 2003; 31(9): 779–783.
  40. Walter A, Reuter C, Fraunberger P, et al. Hypocholesterolemia in cancer. Atherosclerosis. 2000; 151(1): 319.
  41. Teraoka N, Mutoh M, Takasu S, et al. Inhibition of intestinal polyp formation by pitavastatin, a HMG-CoA reductase inhibitor. Cancer Prev Res (Phila). 2011; 4(3): 445–453.
  42. Hu M, Mak V, Chu T, et al. Pharmacogenetics of HMG-CoA Reductase Inhibitors: Optimizing the Prevention of Coronary Heart Disease. Current Pharmacogenomics and Personalized Medicine. 2009; 7(1): 1–26.
  43. Riganti C, Miraglia E, Viarisio D, et al. Nitric oxide reverts the resistance to doxorubicin in human colon cancer cells by inhibiting the drug efflux. Cancer Res. 2005; 65(2): 516–525.

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

Wydawcą serwisu jest VM Media sp. z o.o. VM Group sp.k., ul. Świętokrzyska 73, 80–180 Gdańsk

tel.:+48 58 320 94 94, faks:+48 58 320 94 60, e-mail: viamedica@viamedica.pl