Revealing Vitiligo's Hidden Power: An Unexpected Defense Against Non-Melanoma Skin Cancer

Original Article: The Risk of Keratinocyte Cancer in Vitiligo and the Potential Mechanisms Involved

What are the key takeaways of this article?

Vitiligo is a skin disorder characterized by depigmented patches that affect approximately 0.5-2% of the global population. Vitiligo is not influenced by skin phototype and is primarily mediated by an autoimmune response against melanocytes. Its pathogenesis includes genetic predisposition, environmental factors, and oxidative stress.

Nonmelanoma skin cancers (NMSCs) or keratinocyte cancers (KCs), including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), represent the most common malignancies in individuals with lighter skin types. The increasing incidence of NMSCs is attributed to factors such as prolonged UV exposure, immunosuppressive medication use, and the aging of the population. While prior research has shown that the distinct immunological profile in patients with vitiligo seems to confer protection against melanoma, this study focuses on the risk of NMSCs in patients with vitiligo.

A systematic review and meta-analysis involving nine studies was conducted to ascertain the risk of NMSCs in patients with vitiligo compared to healthy controls. The common effects model yielded an overall risk ratio of 0.66, while the random effects model produced a ratio of 0.60. Both models point to a consistent and compelling result: patients with vitiligo have a decreased risk of developing NMSCs.

To unravel the underlying mechanisms of this intriguing association, researchers have proposed both immune and non-immune mechanisms:

Immune Mechanisms:

Studies suggest that heightened natural killer cell immune surveillance in vitiligo, driven by an inflammatory environment, may possess antitumorigenic properties, thereby reducing the risk of KCs. Additionally, decreased T regulatory cells, commonly associated with autoimmunity in vitiligo, could lead to increased immune surveillance, further lowering the risk of KCs. Elevated CD8+ T-cell immunity against melanocytes, leading to the secretion of IFN-γ in vitiligo, may induce apoptosis in keratinocytes, offering protection against KC, particularly BCC. B-cell elevation in vitiligo facilitates innate immune cell recruitment, playing a pivotal role in preventing KC tumor development.

Non-Immune Mechanisms:

The commonly mutated tumor suppressor gene TP53 retains its wild-type function in vitiligo-afflicted skin, possibly acting as a protective factor against NMSC. The role of elevated TP53 levels in vitiligo remains unclear, but it may promote DNA repair and apoptosis, reducing KC risk. Lastly, dysregulated microRNAs in vitiligo have been shown to downregulate oncogenic transcription factors associated with NMSC, offering a potential mechanism for the lower risk of developing NMSC.

Intriguingly, despite the well-established link between lighter skin types and an increased risk of NMSC, this study provides compelling evidence that patients with vitiligo have a reduced risk of developing KC. While this research presents potential hypotheses explaining this phenomenon, further investigations are imperative to validate these mechanisms. A comprehensive understanding of this association not only advances our knowledge of vitiligo pathogenesis but also informs vitiligo patient counseling, particularly regarding skin cancer surveillance.

Publication Date: November 3rd, 2023

Reference: Rooker A, Ouwerkerk W, Bekkenk MW, Luiten RM, Bakker WJ. The Risk of Keratinocyte Cancer in Vitiligo and the Potential Mechanisms Involved. J Invest Dermatol. 2023 Oct 2:S0022-202X(23)02566-6. doi: 10.1016/j.jid.2023.08.012. Epub ahead of print. PMID: 37791932.

Summary by: Sascha Azoulay