Colchicine Significantly Reduces Incident Cancer in Gout Male Patients: A 12-Year Cohort Study

Ming-Chun Kuo, Shun-Jen Chang, Ming-Chia Hsieh, Ming-Chun Kuo, Shun-Jen Chang, Ming-Chia Hsieh

Abstract

Patients with gout are more likely to develop most cancers than subjects without gout. Colchicine has been used for the treatment and prevention of gouty arthritis and has been reported to have an anticancer effect in vitro. However, to date no study has evaluated the relationship between colchicine use and incident cancers in patients with gout. This study enrolled male patients with gout identified in Taiwan's National Health Insurance Database for the years 1998 to 2011. Each gout patient was matched with 4 male controls by age and by month and year of first diagnosis, and was followed up until 2011. The study excluded those who were diagnosed with diabetes or any type of cancer within the year following enrollment. We calculated hazard ratio (HR), aged-adjusted standardized incidence ratio, and incidence of 1000 person-years analyses to evaluate cancer risk. A total of 24,050 male patients with gout and 76,129 male nongout controls were included. Patients with gout had a higher rate of incident all-cause cancers than controls (6.68% vs 6.43%, P = 0.006). A total of 13,679 patients with gout were defined as having been ever-users of colchicine and 10,371 patients with gout were defined as being never-users of colchicine. Ever-users of colchicine had a significantly lower HR of incident all-cause cancers than never-users of colchicine after adjustment for age (HR = 0.85, 95% CI = 0.77-0.94; P = 0.001). In conclusion, colchicine use was associated with a decreased risk of incident all-cause cancers in male Taiwanese patients with gout.

Conflict of interest statement

The authors have no conflicts of interest to disclose.

Figures

FIGURE 1
FIGURE 1
The study population inclusion algorithms.
FIGURE 2
FIGURE 2
Cumulative hazard risk of incident all-cause cancers in colchicine ever-users and never-users among gout patients (P < 0.001).

References

    1. Chang SJ, Tsai PC, Chen CJ, et al. The polymorphism −863C/A in tumour necrosis factor-alpha gene contributes an independent association to gout. Rheumatology 2007; 46:1662–1666.
    1. Chang SJ, Tsai MH, Ko YC, et al. The cyclic GMP-dependent protein kinase II gene associates with gout disease: identified by genome-wide analysis and case-control study. Ann Rheum Dis 2009; 68:1213–1219.
    1. Coussens LM, Werb Z. Inflammation and cancer. Nature 2002; 420:860–867.
    1. Chang SJ, Chen CJ, Tsai FC, et al. Associations between gout tophus and polymorphisms 869T/C and −509C/T in transforming growth factor beta1 gene. Rheumatology 2008; 47:617–621.
    1. Chen CJ, Yen JH, Chang SJ. Gout patients have an increased risk of developing most cancers, especially urological cancers. Scand J Rheumatol 2014; 43:385–390.
    1. Cocco G, Chu DC, Pandolfi S. Colchicine in clinical medicine. A guide for internists. Eur J Intern Med 2010; 21:503–508.
    1. Finkelstein Y, Aks SE, Hutson JR, et al. Colchicine poisoning: the dark side of an ancient drug. Clin Toxicol (Phila) 2010; 48:407–414.
    1. Imazio M, Bobbio M, Cecchi E, et al. Colchicine in addition to conventional therapy for acute pericarditis: results of the COlchicine for acute PEricarditis (COPE) trial. Circulation 2005; 112:2012–2016.
    1. Imazio M, Brucato A, Trinchero R, et al. Colchicine for pericarditis: hype or hope? Eur Heart J 2009; 30:532–539.
    1. Kallinich T, Haffner D, Niehues T, et al. Colchicine use in children and adolescents with familial Mediterranean fever: literature review and consensus statement. Pediatrics 2007; 119:e474–e483.
    1. Levy M, Spino M, Read SE. Colchicine: a state-of-the-art review. Pharmacotherapy 1991; 11:196–211.
    1. Malawista SE, Seegmiller JE. The effect of pretreatment with colchicine on the inflammatory response to microcrystalline urate: a model for gouty inflammation. Ann Intern Med 1965; 62:648–657.
    1. Bhattacharyya B, Panda D, Gupta S, et al. Anti-mitotic activity of colchicine and the structural basis for its interaction with tubulin. Med Res Rev 2008; 28:155–183.
    1. Lu Y, Chen J, Xiao M, et al. An overview of tubulin inhibitors that interact with the colchicine binding site. Pharm Res 2012; 29:2943–2971.
    1. Stanton RA, Gernert KM, Nettles JH, et al. Drugs that target dynamic microtubules: a new molecular perspective. Med Res Rev 2011; 31:443–481.
    1. Sivakumar G. Colchicine semisynthetics: chemotherapeutics for cancer? Curr Med Chem 2013; 20:892–898.
    1. Desai A, Mitchison TJ. Microtubule polymerization dynamics. Annu Rev Cell Dev Biol 1997; 13:83–117.
    1. Mistry SJ, Atweh GF. Role of stathmin in the regulation of the mitotic spindle: potential applications in cancer therapy. Mt Sinai J Med 2002; 69:299–304.
    1. Lin ZY, Wu CC, Chuang YH, et al. Anti-cancer mechanisms of clinically acceptable colchicine concentrations on hepatocellular carcinoma. Life Sci 2013; 93:323–328.
    1. Craig DH, Owen CR, Conway WC, et al. Colchicine inhibits pressure-induced tumor cell implantation within surgical wounds and enhances tumor-free survival in mice. J Clin Invest 2008; 118:3170–3180.
    1. Fakih M, Yagoda A, Replogle T, et al. Inhibition of prostate cancer growth by estramustine and colchicine. Prostate 1995; 26:310–315.
    1. Michael HP, David SG, Obert TK. Gout and its comorbidities. Bull NYU Hosp Jt Dis 2010; 68:199–203.
    1. Choi HK, De Vera MA, Krishnan E. Gout and the risk of type 2 diabetes among men with a high cardiovascular risk profile. Rheumatology 2008; 47:1567–1570.
    1. Hsieh MC, Lee TC, Cheng SM, et al. The influence of type 2 diabetes and glucose-lowering therapies on cancer risk in the Taiwanese. Exp Diabetes Res 2012; 2012:413782.
    1. El-Serag HB, Hampel H, Javadi F. The association between diabetes and hepatocellular carcinoma: a systematic review of epidemiologic evidence. Clin Gastroenterol Hepatol 2006; 4:369–380.
    1. Larsson SC, Mantzoros CS, Wolk A. Diabetes mellitus and risk of breast cancer: a meta-analysis. Int J Cancer 2007; 121:856–862.
    1. Huxley R, Ansary-Moghaddam A, Berrington de González A, et al. Type-II diabetes and pancreatic cancer: a meta-analysis of 36 studies. Br J Cancer 2005; 92:2076–2083.
    1. Larsson SC, Orsini N, Brismar K, et al. Diabetes mellitus and risk of bladder cancer: a meta-analysis. Diabetologia 2006; 49:2819–2823.
    1. Larsson SC, Orsini N, Wolk A. Diabetes mellitus and risk of colorectal cancer: a meta-analysis. J Natl Cancer Inst 2005; 97:1679–1687.
    1. Kuo CF, Luo SF, See LC, et al. Increased risk of cancer among gout patients: a nationwide population study. Joint Bone Spine 2012; 79:375–378.
    1. Arrieta O, Rodriguez-Diaz JL, Rosas-Camargo V, et al. Colchicine delays the development of hepatocellular carcinoma in patients with hepatitis virus-related liver cirrhosis. Cancer 2006; 107:1852–1858.
    1. Bhattacharyya B, Panda D, Gupta S, et al. Anti-mitotic activity of colchicine and the structural basis for its interaction with tubulin. Med Res Rev 2008; 28:155–183.
    1. Stanton RA, Gernert KM, Nettles JH, et al. Drugs that target dynamic microtubules: a new molecular perspective. Med Res Rev 2011; 31:443–481.
    1. Sivakumar G. Colchicine semisynthetics: chemotherapeutics for cancer? Curr Med Chem 2013; 20:892–898.
    1. Darshan MS, Loftus MS, Thadani-Mulero M, et al. Taxane-induced blockade to nuclear accumulation of the androgen receptor predicts clinical responses in metastatic prostate cancer. Cancer Res 2011; 71:6019–6029.
    1. Gan L, Chen S, Wang Y, et al. Inhibition of the androgen receptor as a novel mechanism of taxol chemotherapy in prostate cancer. Cancer Res 2009; 69:8386–8394.
    1. Jordan MA, Wilson L. Microtubules as a target for anticancer drugs. Nat Rev Cancer 2004; 4:253–265.
    1. Christiansen JJ, Weimbs T, Bander N, et al. Differing effects of microtubule depolymerizing and stabilizing chemotherapeutic agents on t-SNARE-mediated apical targeting of prostate-specific membrane antigen. Mol Cancer Ther 2006; 5:2468–2473.
    1. Li H, Wu WK, Zheng Z, et al. 2,3′,4,4′,5′-Pentamethoxy-trans-stilbene, a resveratrol derivative, is a potent inducer of apoptosis in colon cancer cells via targeting microtubules. Biochem Pharmacol 2009; 78:1224–1232.
    1. Chopra A, Anderson A, Giardina C. Novel piperazine-based compounds inhibit microtubule dynamics and sensitize colon cancer cells to tumor necrosis factor-induced apoptosis. J Biol Chem 2014; 289:2978–2991.

Source: PubMed

3
S'abonner