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Mutagenesis 2004 19(5):399-401; doi:10.1093/mutage/geh048
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Mutagenesis vol. 19 no. 5 © UK Environmental Mutagen Society 2004; all rights reserved.

TP53 mutations in squamous-cell carcinomas of the conjunctiva: evidence for UV-induced mutagenesis

Charles Ateenyi-Agaba1, Min Dai2, Florence Le Calvez2, Edward Katongole-Mbidde3, Anouk Smet2, Massimo Tommasino2, Silvia Franceschi2, Pierre Hainaut2 and Elisabete Weiderpass2,4–,6

1Department of Ophthalmology, Makerere University, PO Box 7072, Kampala, Uganda, 2International Agency for Research on Cancer, World Health Organization, 150 Cours Albert Thomas, 69372 Lyon Cedex 08, France, 3Uganda Cancer Institute, PO Box 7051, Kampala, Uganda, 4Department of Epidemiology and Biostatistics, Karolinska Institutet, PO Box 281, S-17177 Stockholm, Sweden, 5Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Liisankatu 21 B, FIN-00170 Helsinki, Finland and Cancer Registry of Norway, Oslo, Norway

Squamous cell carcinoma of the conjunctiva is associated with sun exposure and often occurs in HIV-positive individuals. We have analysed TP53 mutations in 21 cases of squamous cell carcinoma and 22 controls with benign conjunctival lesions from a region (Uganda, Africa) with a high prevalence of heavy sun exposure and HIV infection. TP53 mutations were detected in 11 cases (52%) and 3 controls (14%). Seven of the mutations (6 in cases and 1 in controls) were CC->TT transitions, a molecular signature of mutagenesis by solar UV rays. A similar prevalence (56%) of TP53 mutations was found in 18 squamous cell carcinoma cases positive for epidermodysplasia verruciformis human papillomavirus types. The prevalence of CC->TT transitions reported here is the highest observed in any cancer type and matches that of skin cancers in subjects with xeroderma pigmentosum, an inherited disease with hypersensitivity to UV damage. These results confirm at the molecular level the causal role of solar UV rays in the aetiology of squamous cell carcinoma of the conjunctiva and suggest that infection with epidermodysplasia verruciformis types of human papillomavirus may act as a cofactor to increase the sensitivity of conjunctiva cells to UV-induced mutagenesis.

6 To whom correspondence should be addressed at: Finnish Cancer Registry, Institute for Statistical and Epidemiological Cancer Research, Liisankatu 21 B, FIN-00170 Helsinki, Finland. Tel: +358 9 135 33274; Fax: +358 9 135 5378; Email: elisabete.weiderpass{at}cancer.fi


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