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Understanding BCC

Epidemiology

Basal cell carcinoma (BCC) is the most prevalent type of non-melanoma skin cancer worldwide.1,2 It affects one in five Americans and more than 3.3 million people annually.2,3 If left untreated or treated inadequately, BCC can cause significant local tissue destruction and disfigurement.2 Mortality is uncommon and metastasis occurs in 1% of cases.2

Pathogenesis

The Sonic Hedgehog (SHH) pathway plays a crucial role in developing and maintaining various organs in mammals. Aberrations in this pathway are significant in the pathogenesis of BCC. When the SHH pathway is activated, SHH binds to Patched (PTCH) on the cell membrane, accumulating Smoothened (SMO) and initiating a downstream signaling cascade—this cascade results in the transcription of target genes that drive the progression of BCC. Blocking SHH can help deactivate this carcinogenic process.4

Immune Dysfunction and Tumorigenesis

UV light exposure is the primary risk factor for BCC, leading to tumors with high mutational burdens. These highly mutated tumors often express immunogenic tumor neoantigens that attract effector T cells. The cancer immunity cycle, which can be self-propagating, involves several steps, from releasing antigens by cancer cells to killing these cells by cytotoxic T lymphocytes (CTLs). However, in cancer patients, this cycle is often dysfunctional, leading to ineffective immune responses against tumors.5 In Figure 2, the individual steps are described, with the primary cell types involved and the anatomic location of the activity.

In short, the cancer antigens (1) are presented by dendritic cells (DCs) to T cells (2), resulting in priming/activation (3) of effector T cells with T cell responses against the cancer-specific antigens that are recognized as foreign. The activated effector T cells travel to (4) and infiltrate (5) the tumor, where they specifically recognize and bind to cancer cells through the interaction between their T cell receptor (TCR) and its antigen bound to MHCI (6). The cytotoxic T lymphocytes (CTLs) then kill their target cancer cell (7), releasing more antigens and amplifying and broadening the immune response.5

Risk Factors

BCC is caused by DNA damage to basal cells in the skin, primarily due to UV radiation from the sun or indoor tanning (Skin Cancer Foundation).1,6 Other risk factors include:

  • History of Skin Cancer: Previous skin cancers, such as squamous cell carcinoma or melanoma, increase the risk.1
  • Age: Most BCC cases occur in people over 50.1
  • Skin Type: Lighter skin that burns easily, rarely tans, or is sensitive to the sun is at higher risk.1,6
  • Gender: Men are more likely to develop BCC.1
  • Chronic Skin Conditions: Infections, inflammation, burns, and scars increase the risk.1
  • Occupation: Jobs with high sun exposure, such as farming, roofing, and military service, elevate risk.6
  • Immune System: A weakened immune system, whether due to medical conditions or treatments, increases BCC risk.6
  • Specific Conditions: Conditions like nevoid basal cell carcinoma syndrome, xeroderma pigmentosum, and others can lead to multiple BCCs.6
  • Previous Treatments: Over 100 PUVA sessions, X-ray treatments for acne, or dialysis for kidney disease increase risk.6
  • Arsenic Exposure: High levels of arsenic in food or water elevate BCC risk.6

While these risk factors increase the likelihood of developing BCC, it can also occur in individuals without any known risk factors, affecting people of all skin colors, including those of African, Asian, and Latin descent.6

References

  1. The Skin Cancer Foundation. Basal cell carcinoma risk factors. (https://www.skincancer.org/skin-cancer-information/basal-cell-carcinoma/bcc-causes-and-risk-factors/). Last updated May 2024.
  2. McDaniel B, Badri T, Steele RB. Basal Cell Carcinoma. In: StatPearls. StatPearls Publishing. Last updated March 13, 2024. (https://www.ncbi.nlm.nih.gov/books/NBK482439/).
  3. Work Group; Invited Reviewers, Kim JYS, et al. Guidelines of care for the management of basal cell carcinoma. J Am Acad Dermatol. 2018;78:540-559. doi:10.1016/j.jaad.2017.10.006
  4. Carballo GB, Honorato JR, de Lopes GPF, Spohr TCLSE. A highlight on Sonic hedgehog pathway. Cell Commun Signal. 2018;16:11. doi:10.1186/s12964-018-0220-7
  5. Chen DS, Mellman I. Oncology meets immunology: The cancer-immunity cycle. Immunity. 2013;39:1-10. doi:10.1016/j.immuni.2013.07.012
  6. American Academy of Dermatology Association. Skin cancer types: Basal cell carcinoma causes. Last updated April 28, 2023 (https://www.aad.org/public/diseases/skin-cancer/types/common/bcc/causes).

All URLs accessed June 24, 2024

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