UV dose determines key characteristics of nonmelanoma skin cancer.

Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), known as nonmelanoma skin cancer (NMSC), are the most common cancers worldwide. Although many factors are involved in the pathogenesis of NMSC, UV radiation is an important risk factor. A fundamental question in skin cancer research is whether varying doses of total UV radiation influence key characteristics of NMSC. The hypothesis that differences in UV doses influence the BCC/SCC ratio, number of tumors, and anatomic location of the tumor was investigated in 311 participants having 326 tumors and with exposure to a broad range of UV doses. An epidemiologic questionnaire was given to each participant soliciting detailed information on exposure to solar radiation. Environmental UVA and UVB doses were measured continually for 6 years at a permanent UV monitoring station. The total ratio of BCC/SCC was 3.5. Participants who received low and high UV doses had a BCC/SCC ratio of 4.2. Those who received very high UV doses had a ratio of 2.1. A very high UV dose was also associated with the doubling of the total number of tumors per person and a significantly increased risk of having SCC, a more aggressive malignancy. Tumors in sun-exposed areas (on the body) were more common in participants who received high and very high UV doses. The tumors in sun-protected areas were associated with exposure to lower levels of UV. This large-scale population study provides evidence that varying doses of UV radiation have a profound influence on key characteristics of NMSC.

[1]  E. D. Smith,et al.  Cost of Nonmelanoma Skin Cancer Treatment in the United States , 2001, Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.].

[2]  J. Parrish,et al.  The interaction of UVA and UVB in the production of threshold erythema. , 1982, The Journal of investigative dermatology.

[3]  M. Karagas,et al.  Occurrence of other cancers among patients with prior basal cell and squamous cell skin cancer. , 1998, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[4]  S. Kurata,et al.  Perineural and Neural Involvement in Skin Cancers , 1997, Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.].

[5]  R. Kirsner,et al.  Squamous Cell Carcinoma Arising in Osteomyelitis and Chronic Wounds: Treatment with Mohs Micrographic Surgery vs Amputation , 1996, Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.].

[6]  Jaime F Abarca,et al.  Skin cancer and ultraviolet‐B radiation under the Antarctic ozone hole: southern Chile, 1987–2000 , 2002, Photodermatology, photoimmunology & photomedicine.

[7]  C. Scaletta,et al.  Protection against pyrimidine dimers, p53, and 8-hydroxy-2'-deoxyguanosine expression in ultraviolet-irradiated human skin by sunscreens: difference between UVB + UVA and UVB alone sunscreens. , 2001, The Journal of investigative dermatology.

[8]  W. M. Sams,et al.  The Biologic Effects of Ultraviolet Radiation , 1970 .

[9]  M. A. Everett,et al.  The Biologic Effects of Ultraviolet Radiation , 1970 .

[10]  H. Griffiths,et al.  Molecular and cellular effects of ultraviolet light-induced genotoxicity. , 1998, Critical reviews in clinical laboratory sciences.

[11]  F. D. de Gruijl,et al.  Mutations in cancer genes of UV-induced skin tumors of hairless mice. , 1999, Journal of epidemiology.

[12]  M. Kripke,et al.  Ultraviolet radiation and immunology: something new under the sun--presidential address. , 1994, Cancer research.

[13]  M. Kripke,et al.  The immune system in ultraviolet carcinogenesis. , 1996, The journal of investigative dermatology. Symposium proceedings.

[14]  M. Ueda,et al.  UV-induced skin damage. , 2003, Toxicology.

[15]  L. Talve,et al.  UVA irradiation increases the incidence of epithelial tumors in UVB-irradiated hairless mice. , 1990, Photodermatology, photoimmunology & photomedicine.

[16]  F. Gruijl Ultraviolet radiation and tumor immunity. , 2002 .

[17]  F. D. de Gruijl Ultraviolet radiation and tumor immunity. , 2002, Methods.

[18]  Stella M. Yu Healthy People 2010 , 1998, Maternal and Child Health Journal.

[19]  R. Strange,et al.  Risk Factors for Basal Cell Carcinoma in the UK: Case-Control Study in 806 Patients , 1997, Journal of the Royal Society of Medicine.

[20]  Latitudinal UVR-PAR measurements in Argentina: extent of the 'ozone hole' , 1997 .

[21]  F. Gruijl,et al.  Mutations in cancer genes of UV-induced skin tumors of hairless mice. , 1999 .

[22]  Andrew G Smith,et al.  Presentation with multiple cutaneous basal cell carcinomas: association of glutathione S-transferase and cytochrome P450 genotypes with clinical phenotype. , 1999, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[23]  V. Devita,et al.  Cancer : Principles and Practice of Oncology , 1982 .

[24]  S. Freeman,et al.  Excision repair of pyrimidine dimers induced by simulated solar radiation in the skin of patients with basal cell carcinoma. , 1990, The Journal of investigative dermatology.

[25]  B. Armstrong,et al.  The epidemiology of UV induced skin cancer. , 2001, Journal of photochemistry and photobiology. B, Biology.

[26]  H. Wanebo,et al.  Prognostic and therapeutic use of microstaging of cutaneous squamous cell carcinoma of the trunk and extremities , 1985, Cancer.

[27]  R. Dummer,et al.  Immunotherapy for nonmelanoma skin cancer , 2002, Cancer.

[28]  Robert Jackson Geographic Pathology of Skin Cancer , 1999, Journal of cutaneous medicine and surgery.

[29]  F. Gruijl Photocarcinogenesis: UVA vs. UVB Radiation , 2002 .

[30]  A. Gaspari,et al.  Immunotherapy of Basal Cell Carcinoma: Evolving Approaches , 2003, Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.].

[31]  K Magnus,et al.  The nordic profile of skin cancer incidence. A comparative epidemiological study of the three main types of skin cancer , 1991, International journal of cancer.

[32]  A. Plana-Fattori,et al.  An Overview of the Ultraviolet Index and the Skin Cancer Cases in Brazil¶ , 2003, Photochemistry and photobiology.

[33]  H. Mukhtar,et al.  Kinetics of UV Light–induced Cyclobutane Pyrimidine Dimers in Human Skin In Vivo: An Immunohistochemical Analysis of both Epidermis and Dermis , 2000, Photochemistry and photobiology.

[34]  M. Herlyn,et al.  Ultraviolet B–induced squamous epithelial and melanocytic cell changes in a xenograft model of cancer development in human skin , 1998, Molecular carcinogenesis.

[35]  R. Carroll,et al.  Prognostic factors for local recurrence, metastasis, and survival rates in squamous cell carcinoma of the skin, ear, and lip. Implications for treatment modality selection. , 1992, Journal of the American Academy of Dermatology.

[36]  L. Grossman,et al.  DNA repair and nonmelanoma skin cancer in Puerto Rican populations. , 2003, Journal of the American Academy of Dermatology.

[37]  L Grossman,et al.  DNA repair and aging in basal cell carcinoma: a molecular epidemiology study. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[38]  S. Ullrich PHOTOIMMUNE SUPPRESSION AND PHOTOCARCINOGENESIS , 2002 .

[39]  F. Gruijl,et al.  Early p53-positive foci as indicators of tumor risk in ultraviolet-exposed hairless mice: kinetics of induction, effects of DNA repair deficiency, and p53 heterozygosity. , 2001, Cancer research.

[40]  P. Buettner,et al.  Incidence rates of skin cancer in Townsville, Australia , 1998, International journal of cancer.

[41]  Steven R Feldman,et al.  Skin cancer is among the most costly of all cancers to treat for the Medicare population. , 2003, Journal of the American Academy of Dermatology.

[42]  J. Cadet,et al.  Bipyrimidine photoproducts rather than oxidative lesions are the main type of DNA damage involved in the genotoxic effect of solar UVA radiation. , 2003, Biochemistry.

[43]  R. Barnhill,et al.  Prognostic factors for cutaneous squamous cell and basal cell carcinoma. Determinants of risk of recurrence, metastasis, and development of subsequent skin cancers. , 1997, Surgical oncology clinics of North America.

[44]  K. Hemminki,et al.  In situ repair of cyclobutane pyrimidine dimers and 6-4 photoproducts in human skin exposed to solar simulating radiation. , 1999, The Journal of investigative dermatology.

[45]  F. D. de Gruijl Photocarcinogenesis: UVA vs. UVB Radiation , 2002, Skin Pharmacology and Physiology.

[46]  C. Potten,et al.  Sensitivity to Sunburn Is Associated with Susceptibility to Ultraviolet Radiation–Induced Suppression of Cutaneous Cell–Mediated Immunity , 2000, The Journal of experimental medicine.

[47]  G. Pfeifer,et al.  Cyclobutane pyrimidine dimers form preferentially at the major p53 mutational hotspot in UVB-induced mouse skin tumors. , 2000, Carcinogenesis.