New Concepts for Basal Cell Carcinoma. Demographic, Clinical, Histological Risk Factors, and Biomarkers. A Systematic Review of Evidence Regarding Risk for Tumor Development, Susceptibility for Second Primary and Recurrence

Basal cell carcinoma (BCC) is the commonest cancer in Caucasians and its incidence is increasing. Whilst ultraviolet radiation (UVR) is recognized as the main etiological factor, the relationship between exposure and host phenotype is still unclear. We systematically searched Medline, Embase, and the Cochrane databases for studies assessing the genetic basis of host response to UVR DNA damage, the effect of UVR on generation of reactive oxygen species (ROS), and their detoxification, UVR induced skin immunity modifications, and the role of genomic instability with a focus on the potential use of these biomarkers to the surgical treatment planning and prognosis of BCC patients. Data suggest that risk for BCC development is likely to result from the combined effect of many genes, each with a relatively weak individual contribution. Certain genomic alterations have been associated with increased or reduced risk for BCC development, with a second primary BCC or with recurrence of BCC. However, use of these biomarkers in everyday practice should be supported by further studies, mainly for its cost-effectiveness. In addition, not enough information exists on the prognostic value of existing demographic and clinical risk predictors for BCC regarding development of second primary or recurrent tumors. Information reviewed suggests that these predictors are of higher predictive value compared with biomarkers whilst they are indisputably cheaper and easier to monitor even in developing countries. Conclusively, we suggest that further studies aimed in investigating second primary or recurrent BCC are needed to provide better information on the predictive value of certain demographic, clinical and histological factors.