Skip to main content

Advertisement

Log in

For Patients with Colorectal Cancer, the Long-Term Use of Statins Is Associated with Better Clinical Outcomes

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

Abbreviations

CRC:

Colorectal cancer

AP:

Adenomatous polyps

HMG-CoA:

3-Hydroxy-3-methyl glutaryl coenzyme A

NSAIDs:

Non-steroidal anti-inflammatory drugs

BMI:

Body mass index

References

  1. 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.

    Article  PubMed  Google Scholar 

  2. 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.

    Article  PubMed  CAS  Google Scholar 

  3. Jakobisiak M, Golab J. Potential antitumor effects of statins. Int J Oncol. 2003;23:1055–1069. Review.

    PubMed  CAS  Google Scholar 

  4. 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.

    Article  PubMed  CAS  Google Scholar 

  5. 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.

    PubMed  CAS  Google Scholar 

  6. 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.

    Article  PubMed  CAS  Google Scholar 

  7. 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.

    Article  PubMed  CAS  Google Scholar 

  8. 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.

    PubMed  CAS  Google Scholar 

  9. Zielinski SL. Following positive epidemiologic studies, statins to enter clinical trials for cancer prevention. J Natl Cancer Inst. 2005;97:1172–1173.

    PubMed  Google Scholar 

  10. Bhuket TP, Higgins PD. Drug insight: statins and gastrointestinal cancer. Nat Clin Pract Gastroenterol Hepatol. 2006;3:552–562. doi:10.1038/ncpgasthep0603.

    Article  PubMed  CAS  Google Scholar 

  11. 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.

    Article  PubMed  CAS  Google Scholar 

  12. 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.

    Article  PubMed  CAS  Google Scholar 

  13. 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.

    Article  PubMed  CAS  Google Scholar 

  14. 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.

    PubMed  CAS  Google Scholar 

  15. 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.

    PubMed  CAS  Google Scholar 

  16. Coogan PF, Smith J, Rosenberg L. Statin use and risk of colorectal cancer. J Natl Cancer Inst. 2007;99:32–40.

    Article  PubMed  Google Scholar 

  17. 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.

    Article  PubMed  Google Scholar 

  18. 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.

    Article  PubMed  CAS  Google Scholar 

  19. 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.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ali A. Siddiqui.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Siddiqui, A.A., Nazario, H., Mahgoub, A. et al. For Patients with Colorectal Cancer, the Long-Term Use of Statins Is Associated with Better Clinical Outcomes. Dig Dis Sci 54, 1307–1311 (2009). https://doi.org/10.1007/s10620-009-0790-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-009-0790-8

Keywords

Navigation