Hydroxymethylglutaryl-CoA reductase inhibitors (statins) have been linked with potential chemopreventive effects; however, the data are conflicting. We conducted a population-based cohort study using data from the Prescription Database of North Jutland County and the Danish Cancer Registry for the period 1989 -2002. In a study population of 334,754 county residents, we compared overall and site-specific cancer incidence among 12,251 statin users (>2 prescriptions) with cancer incidence among nonusers and users of other lipid-lowering drugs (n ‫؍‬ 1,257). Statistical analyses were based on age-standardization and Poisson regression analysis, adjusting for age, gender, calendar period and use of NSAIDs, hormone replacement therapy and cardiovascular drugs. We identified 398 cancer cases among statin users during a mean follow-up period of 3.3 years (range 0 -14 years). The age-and gender-standardized incidence rates of cancer overall were 596 per 100,000 Key words: statins; cancer incidence; risk; epidemiology; cohort study Inhibitors of hydroxymethylglutaryl-CoA reductase (statins) have been linked with several beneficial effects beyond their effect on cardiovascular disease, including reductions in risk of dementia, 1-3 fractures 4 -7 and cancer. 8,9 However, the data on cancer risk are conflicting. In a review of rodent carcinogenicity tests, Newman and Hulley reported that statins and fibrates initiate or promote cancer in rats and mice. 10 In most of the reviewed studies, however, the doses used were substantially higher than the recommended maximum doses for humans, and the employed bioassays were criticised for being inadequate to predict carcinogenicity in humans. 11 In contrast, several recent studies of human cancer cell lines and animal tumour models indicate that statins may have chemopreventive properties by inducing apoptosis and inhibiting tumour growth and metastasis. 12-21 Although a growing body of laboratory data thus indicate that statins may protect against cancer, 8,9 the clinical relevance of these data remain unclear. Results of clinical trials and observational studies of the association between statin use and cancer are inconsistent. [22][23][24][25][26][27][28][29][30][31][32][33][34] A few studies lend some support to a cancer-protective effect, 27,31,33,34 but the majority of the studies do not point to any substantially increased or decreased cancer risk among statin users. The reasons for the varying results are unclear but may relate to methodologic issues, including small sample sizes and short follow-up periods.Given the uncertainty about the effect of statins on cancer development and their widespread and long-term use, more data are needed on the relationship between statins and cancer. Thus, we examined cancer incidence among statin users in a populationbased cohort study in Denmark.

Proton pump inhibitor (PPI) use leads to hypergastrinaemia, which has been associated with gastrointestinal neoplasia. We evaluated the association between PPI use and risk of gastric cancer using population-based health-care registers in North Jutland, Denmark, during 1990Denmark, during -2003. We compared incidence rates among new users of PPI (n ¼ 18 790) or histamine-2-antagonists (H2RAs) (n ¼ 17 478) and non-users of either drug. Poisson regression analysis was used to estimate incidence rate ratios (IRRs) adjusted for multiple confounders. We incorporated a 1-year lag time to address potential reverse causation. We identified 109 gastric cancer cases among PPI users and 52 cases among H2RA users. After incorporating the 1-year lag time, we observed IRRs for gastric cancer of 1.2 (95% CI: 0.8 -2.0) among PPI users and 1.2 (95% CI: 0.8 -1.8) among H2RA users compared with non-users. These estimates are in contrast to significant overall IRRs of 9.0 and 2.8, respectively, without the lag time. In lag time analyses, increased IRRs were observed among PPI users with the largest number of prescriptions or the longest follow-up compared with H2RA users or nonusers. Although our results point to a major influence of reverse causation and confounding by indication on the association between PPI use and gastric cancer incidence, the finding of increased incidence among PPI users with most prescriptions and longest follow-up warrants further investigation.

The absence of an exposure-response relationship either in terms of the amount of mobile phone use or by localization of the brain tumor argues against a causal association.