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Melanoma linked to problems with repairing DNA
By Adam Marcus

Exposure to intense sun at a young age is a major risk factor for melanoma, the most serious form of skin cancer, later in life. The capacity of our cells to repair DNA damaged by sunshine is another risk factor.

Researchers have compared DNA repair activity in the white blood cells of 312 melanoma patients and 324 individuals with no history of the disease. The melanoma patients did not repair damaged DNA as efficiently as others in the study.

The risk of developing melanoma was twice as great for people with poor DNA repair as it was for those whose cells mended damage well, the researchers found.

Vincent van Gogh. Sower with Setting Sun (1888).

The ultraviolet light in sunshine causes mutations in genes that regulate cell growth. People survive regular exposure to sunlight because of genes that repair the damage.

For the average person, skin cells can repair the most intense damage to DNA caused by the mid-day sun, says Qingyi Wei, an epidemiologist at the M.D. Anderson Cancer Center in Houston and a leader of the research team. The findings appear in the Journal of the National Cancer Institute.

"I think this is a landmark study," says Marianne Berwick, an epidemiologist at Memorial Sloan-Kettering Cancer Center in New York who was not involved in the research. "Up until now there have just been hints that melanoma [in the general population] is associated with faulty DNA repair."

The latest study is a "very important advance," adds Kenneth Kraemer, a skin cancer expert at the US National Cancer Institute in Bethesda, Maryland. The findings could eventually lead to molecular tests that identify individuals who are susceptible to melanoma. Doctors currently rely on traits such as eye color and complexion to predict who is most likely to develop skin cancer from sun exposure.

The key genes involved in DNA repair have not yet been identified, though many laboratories are hunting for them. In a previous study, researchers identified eight genes associated with a rare disorder, xeroderma pigmentosa, that can lead to melanoma early in life.

Melanoma will occur in an estimated 54,000 Americans this year, and 7,400 are expected to die from the disease. The condition is three times more common in Australia, but less prevalent in Europe.

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Wei, Q. et al. Repair of UV light-induced DNA damage and risk of cutaneous malignant melanoma. J Natl Cancer Inst 4, 308-315 (February 19, 2003).

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