Use of statins and risk of glioma: a nationwide case–control study in Denmark

Given the widespread and rapidly increasing use of statins, any association with cancer development or progression would have a substantial impact on public health. At present, statins cannot be recommended for primary cancer prevention or therapy because of conflicting evidence (Boudreau et al, 2010). However, preclinical findings of antineoplastic activity of statins warrant their further evaluation as potential chemopreventive agents (Chan et al, 2003; Sassano and Platania, 2008; Tapia-Perez et al, 2010). One line of investigation deserving particular attention is the effect of statins on gliomas, a group of central nervous system tumours of largely unknown aetiology. The most common histological subtype, glioblastoma multiforme, accounts for more than 50% of gliomas, and has an incidence rate of 3.5 per 1 00 000 person-years in Nordic countries and male predominance (Lonn et al, 2004). Laboratory studies of human glioma cell lines indicate that statins may exert antitumour activity through such mechanisms as inhibition of cellular proliferation, growth, migration, and by induction of apoptosis (Jones et al, 1994; Soma et al, 1994; Bouterfa et al, 2000; Obara et al, 2002; Gliemroth et al, 2003; Jiang et al, 2004; Chan et al, 2008; Wu et al, 2009; Yanae et al, 2011). In a phase I/II study of 18 patients with malignant gliomas, lovastatin with and without radiotherapy was well tolerated, but had minimal effect on tumour progression (Larner et al, 1998). To date, only one case–control study has addressed the risk of glioma among statin users (Ferris et al, 2012). This study reported that ⩾6 months of simvastatin use was inversely associated with glioma risk (odds ratio (OR)=0.72; 95% confidence interval (CI): 0.52–1.00). Recall bias was a potential shortcoming of this interview-based study, with information collected from proxies in ∼19% of cases. We therefore conducted a nationwide population-based case–control study utilising registry data to further investigate the association between statin use and glioma risk.