Skin Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Skin Cancer, including details on identification, causes, prevention, treatment.

The XPC poly-AT polymorphism in non-melanoma skin cancer.

Nelson HH, Christensen B, Karagas MR

Department of Environmental Health, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA. hnelson@hsph.harvard.edu

Signature UV-DNA lesions, cyclobutane dimers and 6-4 photoproducts, are repaired via the nucleotide excision repair pathway. NER may be subdivided into transcription-coupled repair and global genome repair, and the XPC protein is specific to this latter repair pathway recognizing helix distorting lesions and initiating their repair. Inactivating XPC mutations are associated with xeroderma pigmentosa and an extremely high risk of skin cancer. A common polymorphism in intron 9 of the XPC gene has been associated with both reduced repair of UV-DNA damage (using the host-cell reactivation assay) and increased risk of squamous cell head and neck cancer. Here, we have tested the hypothesis that the XPC PAT+ polymorphism is associated with non-melanoma skin cancer using a population-based case control study of skin cancer in New Hampshire (n=1917). Overall, there was a modest decreased risk of squamous cell carcinoma (SCC) among those with the homozygous variant PAT+/+ genotype (OR 0.8, 95% CI 0.5-1.1) that was most evident among tanners (OR 0.4, 95% CI 0.1-1.1), however, these trends failed to reach statistical significance. There was no association of the PAT+/+ genotype and basal cell carcinoma (OR 1.0, 95% CO 0.7-1.3), however there was a modest, non-statistically significant, decreased risk among those with the heterozygous genotype (OR 0.8, 95% CI 0.7-1.1). We did not detect gene environment interactions for either SCC or BCC between the XPC PAT genotype and average hours of UV exposure per week, painful sunburn history, nor ionizing radiation therapy. These results suggest that the XPC PAT+polymorphism does not play a major role in non-melanoma skin cancer, but that it may slightly modify the risk of SCC among individuals with a phenotype which results in low UV-DNA adduct burdens. These results require further confirmation.

Published 2 May 2005 in Cancer Lett, 222(2): 205-9.
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