Chromatid breaks impact skin cancer development

Houston - One of the cornerstones of dermatology is the association between overexposure to sunlight and damage it does to the skin.

Breaks in cellular DNA are a principle causal factor in the development of skin cancer, so it was reasonable to hypothesize that as the number of breaks in chromosomes increases, so would the incidence and aggressiveness of the cancer. But as it turns out, the equation isn't quite so simple.

Another important component in the development of skin cancer is the ability of cellular DNA to repair solar damage, says Qingyi Wei, M.D., Ph.D., a researcher at the M.D. Anderson Cancer Center here. Dr. Wei focuses his research on the etiology of skin cancer.

Research specifics

Dr. Wei's research team took lymphocyte samples from patients with various types of skin cancer and from cancer-free controls.

Previous research has shown that response patterns to ultraviolet–B (UVB) are genetic in nature and similar across the types of cells found within a single patient. It was easier and less invasive to obtain samples of lymphocytes.

Researchers subjected the cells to a uniform exposure to UVB, allowed 24 hours for the cells to repair themselves, and then counted the frequency of chromatid breaks per cell.

Breaks' affect on cancer

There was a nearly threefold increased risk for basal cell or squamous cell carcinoma - in a dose-dependent manner - that increased with the number of breaks.

Surprisingly, that did not hold for melanoma, where the number of breaks per cell was closer to the level of the healthy controls than to the other forms of cancer.

The researchers found that:

Using a matrix of physical traits and lifetime experiences, the researchers found that the experimental data generated in this study is consistent with the risk for basal cell carcinoma being associated with intermittent sun exposure. But beyond a certain plateau, that risk did not increase with added sun exposure, as previous population studies had shown. This suggests a genetic predisposition to early onset BCC in the low-dose exposure range.

Development of squamous cell carcinoma was associated with total accrued sun exposure.

Finally, the risk of cutaneous malignant melanoma was strongly associated with intermittent sun exposure, particularly with that which occurred at an early age.

Melanoma findings intriguing

Dr. Wei says the findings on melanoma "were a bit counterintuitive" because those who developed melanoma had so few chromatid breaks.

But he cautions against reading the findings as suggesting that UVB damage does not cause melanoma.

"At the DNA level, I don't think that melanoma is less sensitive to UVB," Dr. Wei explains. "The measure of chromatid breaks is not a good marker for melanoma, for which a direct measure of DNA repair rate is needed.

"Apparently with chromosome breaks, as seen with basal cell and squamous cell carcinomas, the cells either die or they escape and develop cancer rather quickly. Whereas with melanoma, the cells do not die, they hang in there, and that's why it can take 20 years for melanoma to develop," Dr. Wei says.