From the Guidelines
The main drivers of basal cell carcinoma (BCC) are primarily ultraviolet (UV) radiation exposure from sunlight, genetic factors, and compromised immune function, which collectively contribute to DNA damage in skin cells and increase the risk of developing BCC. The most significant risk factors for BCC include:
- Ultraviolet (UV) radiation exposure from sunlight, which causes DNA damage in skin cells 1
- Genetic factors, particularly in people with fair skin, light eyes, and blonde or red hair who have less melanin protection 2
- Inherited conditions like nevoid basal cell carcinoma syndrome (Gorlin syndrome) that predispose individuals to developing multiple BCCs 2
- Compromised immune function, whether from diseases like HIV or medications following organ transplantation, which increases susceptibility 1
- Advanced age, as cumulative sun damage increases over time 1
- Exposure to arsenic, radiation therapy, and certain industrial chemicals, which can also contribute to BCC development 1, 2 It is essential to note that the relationship between sun exposure and BCC is complex, depending on timing, pattern, and amount of UV radiation 1. The carcinoma typically develops when UV radiation damages the DNA in basal cells, particularly affecting the PTCH1 gene in the Hedgehog signaling pathway, leading to uncontrolled cell growth and tumor formation. Patients should be made aware of the various resources that discuss skin cancer prevention, such as the American Cancer Society and the American Academy of Dermatology 1.
From the Research
Main Drivers of Basal Cell Carcinoma
The main drivers of basal cell carcinoma (BCC) can be summarized as follows:
- UV radiation is the most important risk factor in the development of BCC, with short-wavelength UVB radiation playing a greater role than long-wavelength UVA radiation 3
- Cumulative UV radiation exposure, particularly UVB, is a significant environmental risk factor for the occurrence and progress of BCC 4
- Other risk factors for the development of BCC include: + Sun bed use + Family history of skin cancers + Skin type 1 and 2 + Immunosuppression + Previous radiotherapy + Chronic exposure to toxic substances such as inorganic arsenic 3 + Radiation treatment, particularly if experienced before age 20 5
Genetic Alterations
Genetic alterations also play a significant role in the development of BCC, including:
- Mutations in the TP53 tumor-suppressor gene, found in about 50% of BCC cases 3
- Activation of the Hedgehog intercellular signaling pathway genes, including PTCH, Sonic hedgehog (Shh), and Smoothened (Smo) 3, 6
- PTCH1 alterations, found in 93% of BCCs arising at sun-protected sites and 100% of BCCs arising on sun-exposed skin 6
Environmental Factors
Environmental factors that contribute to the development of BCC include:
- UV radiation exposure, which can cause DNA damage and activate oncogenes while inactivating tumor suppressor genes 4
- Inflammatory responses of immune cells in the tumor microenvironment, which play a crucial role in skin tumorigenesis 4
- Cumulative solar ultraviolet radiation exposure, which has been linked to an increased risk of BCC in prospective cohort studies 7