Whole-Exome Sequencing of Vitiligo Lesions Indicates Lower Burden of Somatic Variations: Implications in Risk for Nonmelanoma Skin Cancers

Genetic depigmentary conditions such as albinism with complete loss of epidermal pigmentation pose a higher risk for cutaneous malignancies ( Lekalakala et al., 2015 Lekalakala P.T. Khammissa R.a.G. Kramer B. Ayo-Yusuf O.A. Lemmer J. Feller L. Oculocutaneous albinism and squamous cell carcinoma of the skin of the head and neck in Sub-Saharan Africa. J Skin Cancer. 2015; 2015167847 Crossref PubMed Scopus (31) Google Scholar ; Kromberg et al., 1989 Kromberg J.G. Castle D. Zwane E.M. Jenkins T. Albinism and skin cancer in Southern Africa. Clin Genet. 1989; 36: 43-52 Crossref PubMed Scopus (118) Google Scholar ). By analogy, clinical management for photoprotection of the acquired depigmented skin in vitiligo is of serious concern. It is believed that vitiligo would pose a similar, elevated risk. Systematic evaluation of a large cohort of subjects with vitiligo indicated a decreased risk for both melanoma and nonmelanoma skin cancers ( Hexsel et al., 2009 Hexsel C.L. Eide M.J. Johnson C.C. Krajenta R. Jacobsen G. Hamzavi I. et al. Incidence of nonmelanoma skin cancer in a cohort of patients with vitiligo. J Am Acad Dermatol. 2009; 60: 929-933 Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar ; Kim et al., 2020 Kim H.S. Kim H.J. Hong E.S. Kim K.B. Lee J.D. Kang T.U. et al. The incidence and survival of melanoma and nonmelanoma skin cancer in patients with vitiligo: a nationwide population-based matched cohort study in Korea. Br J Dermatol. 2020; 182: 907-915 Crossref PubMed Scopus (19) Google Scholar ; Paradisi et al., 2014 Paradisi A. Tabolli S. Didona B. Sobrino L. Russo N. Abeni D. Markedly reduced incidence of melanoma and nonmelanoma skin cancer in a nonconcurrent cohort of 10,040 patients with vitiligo. J Am Acad Dermatol. 2014; 71: 1110-1116 Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar ; Rodrigues, 2017 Rodrigues M. Skin cancer risk (nonmelanoma skin cancers/melanoma) in vitiligo patients. 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Extrapolating from demographic studies, it is tempting to speculate that vitiligo could negatively influence either initiation or progression of cutaneous malignancies ( Rodrigues, 2017 Rodrigues M. Skin cancer risk (nonmelanoma skin cancers/melanoma) in vitiligo patients. Dermatol Clin. 2017; 35: 129-134 Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar ). Given the autoimmune etiology that targets melanocyte destruction, protection against melanoma could be rationalized; however, similar protection from nonmelanoma skin cancer is perplexing. Therefore, these observations need to be substantiated with evidence at the tissue level. Recent advancements in genomics enable the mapping of the somatic variations that would act as a molecular correlate for cancer. In normal, seemingly healthy skin, deep sequencing of a selected panel of cancer-associated genes suggests a pervasive positive selection of somatic variations that provides valuable insights into the origin of somatic variations and map their progression to skin cancers ( Martincorena et al., 2015 Martincorena I. Roshan A. Gerstung M. Ellis P. Van Loo P. McLaren S. et al. Tumor evolution. High burden and pervasive positive selection of somatic mutations in normal human skin. Science. 2015; 348: 880-886 Crossref PubMed Scopus (1039) Google Scholar ; Zheng et al., 2021 Zheng Q. Capell B.C. Parekh V. O’Day C. Atillasoy C. Bashir H.M. et al. Whole-exome and transcriptome analysis of UV-exposed epidermis and carcinoma in situ reveals early drivers of carcinogenesis. J Invest Dermatol. 2021; 141: 295-307.e13 Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar ). Lower Skin Cancer Risk in Vitiligo: DNA Repair as Potential Mechanism?Journal of Investigative DermatologyVol. 143Issue 6PreviewVitiligo is an autoimmune disease that targets skin melanocytes, resulting in a localized loss of epidermal melanocytes visible as depigmented skin lesions. Individuals with low skin pigmentation levels generally have an increased risk of skin cancer. However, the incidence of both melanoma and nonmelanoma skin cancer (NMSC) turns out to be lower in patients with vitiligo than in healthy individuals, despite the lack of pigmentation in vitiligo lesions or treatment by UV phototherapy (Paradisi et al., 2014; Teulings et al., 2013). Full-Text PDF