August 1994

The Role of Sunlight and DNA Repair in Melanoma and Nonmelanoma Skin CancerThe Xeroderma Pigmentosum Paradigm

Author Affiliations

From the Laboratory of Molecular Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Md (Drs Kraemer and Lee); the Department of Dermatology, Columbia University College of Physicians and Surgeons, New York, NY (Dr Andrews); and the Departments of Laboratory Medicine and Pathology and Dermatology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ (Dr Lambert). Dr Lee is now with the Division of Dermatology, Department of Family Practice, US Air Force Medical Corps, Yokota (Japan) Air Base Hospital.

Arch Dermatol. 1994;130(8):1018-1021. doi:10.1001/archderm.1994.01690080084012

Background and Design:  The frequency of melanoma and nonmelanoma skin cancer is increasing rapidly in the United States. However, the linkage of these cancers to sun exposure has been questioned because of differences in anatomic site distribution. To obtain insights into the development of these skin cancers, we examined reports of 132 patients with xeroderma pigmentosum (XP), an inherited cancer-prone, DNA repair—deficient disorder with marked clinical and laboratory UV hypersensitivity.

Results:  Malignant skin neoplasms were present in 70% of the patients with XP at a median age of 8 years, which is 50 years earlier than in the US white population. Fifty-seven percent of the patients had basal cell or squamous cell carcinoma, and 22% had melanoma. The frequency of melanomas, like the frequency of nonmelanoma skin cancers (basal cell and squamous cell carcinomas), anterior eye cancers, and tongue cancers, but unlike that of internal neoplasms, was increased 1000-fold or more in patients with XP who were younger than 20 years. As in the general population, the anatomic distribution of melanomas was different from that of nonmelanomas in the patients with XP.

Conclusions:  These data suggest that (1) DNA repair plays a major role in the prevention of cutaneous cancers in the general population and (2) sunlight exposure is responsible for the induction of melanoma as well as nonmelanoma skin cancer in patients with XP, although acting by different mechanisms for the two types of skin cancer.(Arch Dermatol. 1994;130:1018-1021)