The genetics of basal cell carcinoma

Basal cell carcinoma (BCC) is the most common human cancer, with a 30% lifetime risk in those of European descent. Incidence is increasing by 3–10% per annum worldwide and it is expected that, soon, the prevalence will equal that of all other cancers combined. While mortality is rare, BCC causes considerable morbidity and burden on health services. BCCs are slow-growing, locally invasive, malignant epidermal tumours which rarely metastasise (<0.1%). The underlying causal mechanism is a genetic aberration, which may be inherited or acquired. Primary risk factors are ultraviolet (UV) light exposure and genetic predisposition. Other significant risk factors include Fitzpatrick skin types I and II, immunosuppression, advanced age, male sex, previous BCCs and chronic arsenic exposure. Research into the molecular genetics of BCCs in the past two decades has uncovered many of the pathways fundamental to their pathogenesis, leading to potential therapeutic targets. Several targeted agents are currently being trialled; one, vismodegib, is licensed in the UK for use in advanced BCC. Studies to date demonstrate efficacy of these targeted agents, albeit with frequent and considerable side-effects, and evidence of resistance and recurrence, which currently limit their use to a select group of patients. Pathway inhibitors, though in their infancy, offer a novel and exciting avenue for the targeted treatment of BCC.