Skin cancer is the most common type of cancer in fair-skinned populations in many parts of the world. The incidence, morbidity and mortality rates of skin cancers are increasing and, therefore, pose a significant public health concern. Ultraviolet radiation (UVR) is the major etiologic agent in the development of skin cancers. UVR causes DNA damage and genetic mutations, which subsequently lead to skin cancer. A clearer understanding of UVR is crucial in the prevention of skin cancer. This article reviews UVR, its damaging effects on the skin and its relationship to UV immunosuppression and skin cancer. Several factors influence the amount of UVR reaching the earth’s surface, including ozone depletion, UV light elevation, latitude, altitude, and weather conditions. The current treatment modalities utilizing UVR (i.e. phototherapy) can also predispose to skin cancers. Unnecessary exposure to the sun and artificial UVR (tanning lamps) are important personal attributable risks. This article aims to provide a comprehensive overview of skin cancer with an emphasis on carefully evaluated statistics, the epidemiology of UVR-induced skin cancers, incidence rates, risk factors, and preventative behaviors & strategies, including personal behavioral modifications and public educational initiatives.
In this large population-based study, we found no apparent association between long-term use of statins and risk of BCC or SCC. Furthermore, risk estimates for BCC or SCC did not differ materially according to duration, cumulated dose, or type of statin.
Few previous epidemiological studies have addressed the risk of NMSC associated with statin use. In a post-trial analysis of the Veterans Affairs Topical Tretinoin Chemoprevention trial (Dore et al, 2009), no association was found in a propensity score-matched analyses of the study cohort (BCC: RR, 0.92; 95% CI: 0.73–1.16, SCC: RR, 0.88; 95% CI: 0.63–1.23). Another US study (Asgari et al, 2009) reported a neutral RR of 1.01 (95% CI: 0.92–1.12) for secondary BCC among patients with primary BCC, whereas long-term (>5 years) statin use was associated with a slightly increased RR of 1.29 (95% CI: 0.93–1.81). In a large record-linkage study from Finland, long-term (>5 years) statin use was associated with an increased risk of NMSC (RR, 1.33; 95% CI: 1.15–1.54), although tests for trend were significant only for pravastatin (Haukka et al, 2010). No disease-specific estimates were reported for BCC or SCC. Finally, two meta-analyses reported cumulative results on the risk of NMSC associated with statin use (Kuoppala et al, 2008, Li et al, 2014). In the study by Kuoppala et al (2008) that included data only from RCTs of statin, the authors reported a 30–60% (depending on study selection) increased risk of NMSC among statin users. In a more recent meta-analysis, including data from both RCTs and observational studies, no apparent association was found between statin use and NMSC risk (Li et al, 2014). Thus, although methodological issues hamper straightforward comparisons, our finding of no apparent link between use of statin and risk of NMSC is in line with most previous studies.
Our study had a number of strengths. We used a nationwide prescription registry to assess statin use, an approach that provided detailed long-term drug use histories and eliminated recall bias. In Denmark, statins can only be obtained by prescription. Our use of nationwide registries with virtually complete coverage and continuously updated data on demographic characteristics, hospital contacts and cancer outcomes minimised selection bias. During the study period, the registration of NMSC in the DCR was based on reports from the primary health care sector and the patient register combined with diagnoses from the pathology registry, which holds records of all histological examinations of skin biopsies performed by private practitioners and at hospitals. This secured complete ascertainment of histologically verified NMSC cases and allowed evaluation of the association with statin use by histological type of NMSC.
Our study also had some potential limitations. First, we were not able to adjust for differences in sun habits. A high cumulated level of sunlight exposure is associated with an average 3.5-fold excess risk of SSC (English et al, 1998). This level of sunlight exposure has been estimated to pertain to ∼25% of a Western population (English et al, 1998). Using these figures combined with the exposure prevalence of 16% for statins in our study and the ‘rule-out’ approach (Schneeweiss, 2006), we estimated that even a statin–sunlight exposure association as low as 1.38 would fully explain an observed OR of 1.1 for statins and SCC. The slight increase in risk of NMSC associated with statin use observed in our study can therefore easily be explained by residual confounding by sunlight exposure or other unmeasured confounding. According to a recent Danish survey of 13 996 individuals, statin users had less healthy lifestyle profiles than nonusers of the drug; however, that study did not include data on sun light exposure (Thomsen et al, 2013). Second, we cannot exclude some degree of socioeconomic confounding, although the study was conducted in a population with tax-supported free access to health care and, further, adjustment was performed for education in the analyses. A previous Danish survey reported a clear socioeconomic gradient in statin use among men but not women (Thomsen et al, 2005); however, the gradient was markedly lower in the recent survey (Thomsen et al, 2013).
In conclusion, our study does not indicate a major association between statin use and risk of BCC or SCC.