Xeroderma pigmentosum and the role of UV-induced DNA damage in skin cancer.
Xeroderma pigmentosum (XP) is a rare, autosomal recessive disease that is characterized by the extreme sensitivity of the skin to sunlight. Compared to normal individuals, XP patients have a more than 1000-fold increased risk of developing cancer on sun-exposed areas of the skin. Genetic and molecular analyses have revealed that the repair of ultraviolet (UV)-induced DNA damage is impaired in XP patients owing to mutations in genes that form part of a DNA-repair pathway known as nucleotide excision repair (NER). Two other diseases, Cockayne syndrome (CS) and the photosensitive form of trichothiodystrophy (TTD), are linked to a defect in the NER pathway. Strikingly, although CS and TTD patients are UV-sensitive, they do not develop skin cancer. The recently developed animal models that mimic the human phenotypes of XP, CS and TTD will contribute to a better understanding of the etiology of these diseases and the role of UV-induced DNA damage in the development of skin cancer.
van Steeg
H
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National Institute of Public Health and the Environment, Dept of Carcinogenesis, Mutagenesis and Genetics, Bilthoven, The Netherlands. h.van.steeg@rivm.nl
Kraemer
K H
KH
D000818:Animals; D004249:DNA Damage / Q000528:radiation effects; D004195:Disease Models, Animal; D006801:Humans; D012878:Skin Neoplasms / Q000235:genetics*; D013577:Syndrome; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000235:genetics* / Q000503:physiopathology