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Polymorphisms in DNA repair gene XPD may increase risk of skin cancer
By Sharon Guynup

Scottish researchers have unearthed three genetic mutations of the XPD gene that are significantly linked to the incidence of melanoma, the most deadly form of skin cancer.

The nucleotide excision repair (NER) pathway has evolved to restore DNA damaged by ultraviolet light—or kill off cells that are beyond repair. It is a complex process, involving at least 25 proteins, which is synchronized with cellular processes such as transcription and DNA replication. In a recent study, Daniela Tomescu and colleagues, of Edinburgh University, United Kingdom, have investigated whether subtle changes in NER genes might also increase the risk for skin cancer.

The team selected patients likely to have a genetic predisposition to skin cancer from a group being treated for melanoma at the Department of Dermatology at the Royal Infirmary of Edinburgh. The study participants were all under the age of 50, they had no history of extreme sun exposure and were in the earliest stage of the disease.

Skin cancer patients had a higher frequency of polymorphisms in exons 6, 22, and 23 of the XPD gene compared with the control group. Statistical analysis showed a significant correlation between the presence of these mutations and the disease. This suggests that even small changes in excision repair genes might hamper cell repair or alter proteins governing the cell cycle. Over years of exposure to UV rays, even a tiny reduction in the cells' repair capacity could greatly increase the risk for cancer.

A larger study will be needed to confirm these findings and to search for similar associations in other NER genes.

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Tomescu, D. et al. Nucleotide excision repair gene XPD polymorphisms and genetic predisposition to melanoma. Carcinogenesis 22, 403-408 (March 2001).

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