Scotland has one of the highest incidences of colorectal cancer in the world. Colorectal cancer (CRC) is the third most commonly diagnosed cancer in both men and women (15% of cancer cases in men; 11.6% of cancer cases in women). Approximately 3,900 new cases are diagnosed each year and 95% of cases occur in people aged over 50 years. Over recent years both the incidence and mortality rates have fallen for both sexes. However, CRC remains the second most common cause of cancer deaths for men (10.1% of cancer-related deaths) and the third for women (9.6% of cancer related deaths) with approximately 1500 people dying of the disease in Scotland each year
The main risk factors, excluding genetic, for colorectal cancer are dietary, obesity, lack of physical activity and smoking. The prevalence of each of these risk factors is also high in the Scottish population. Additionally, Scotland’s overall health is comparatively poor for a Western county, particularly amongst people of working age. This includes heart disease.
Statins, also known as 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, were first prescribed in Scotland in 1989. They have revolutionised the treatment of hypercholesterolaemia
, by lowering serum cholesterol and reducing cardiac morbidity and mortality in both primary and secondary prevention of coronary artery disease
[2, 3]. There has been a consistent increase in prescribing of statins, which reflects the increase in prescribing of drugs for cardiovascular disease (Additional file
1: Supplementary material 1).
Their beneficial effects are usually attributed to their capacity to reduce endogenous cholesterol synthesis
[4, 5]. They competitively inhibit HMG-CoA reductase, the major rate-limiting enzyme that controls the conversion of HMG-CoA to mevalonic acid (MA)
[6, 7]. These mevalonate-derived prenyl groups enable precise cellular localisation and function of many proteins involved in important intracellular signalling pathways (e.g. Ras and Rho proteins)
[6, 7]. Therefore, besides lowering cholesterol levels, statins exert effects on many essential cellular functions including cell proliferation, differentiation, and survival as well as participating in the regulation of cell shape and motility
. It is these other effects of MA and the fact that many malignant cells present an increased HMG-CoA reductase activity, which suggest that selective inhibition of the HMG-CoA reductase enzyme could lead to a new chemotherapy for cancer disease
Results obtained in vitro have demonstrated that statins possess a number of anti-tumour effects and through a variety of potential mechanisms (Additional file
1: Supplementary material 2). In vivo studies have, in the main, endorsed in vitro results by the display of antitumour effects in numerous animal tumour models resulting in retardation of tumour growth; inhibition of angiogenesis and/or inhibition of the metastatic process
[10–15]. Additionally a number of studies have legitimised the potential of statins to significantly increase the chemopreventive efficacy of other anti-tumour treatments at doses much lower that are needed for their anti-proliferative effects
Epidemiological studies have in the main concentrated on the association with risk of colorectal cancer. Results of these have been inconsistent (Additional file
1: Supplementary material 3 and 4) and the exact role of statins remains to be elucidated. More recently there has been a growing interest in the association of statins with disease progression and survival. The former has been explored in only two studies
[22, 23] and the latter in one
. Findings from these indicated that long term use of statins may be associated with a less advanced tumour stage and a better survival rate
The objective, addressed by this study, was to explore the association between statin use and colorectal cancer risk, progression and survival in a Scottish population. To date no study has investigated these associations of statin use and CRC in a Scottish population and data otherwise remains inconclusive.