Researchers may have found a more potent risk factor for melanoma than blistering sunburns, freckling, or family history of the deadly skin disease. In a new study, scientists at NYU Langone Medical Center report that a genetic variation leads to a nearly four-fold increase of melanoma in women under the age of 50.
"Potentially, we have a genetic test that might identify pre-menopausal women who are at higher risk for melanoma," said Dr. Polsky. "And if that's the case, then we might want to have increased surveillance of those patients including more frequent visits to the doctor, more rigorous teaching of skin self-examination, and other preventive steps." For largely unknown reasons, melanoma is more common among women than men under the age of 40.
Polsky and his co-authors suspect the difference may be linked to the activity of estrogen, mediated in part by a genetic variant in a gene called MDM2. When estrogen binds to this gene, it turns on production of MDM2, a potential oncogene (cancer promoting gene) in cells. In the presence of the genetic variation in MDM2, originally identified by the laboratory of Dr. Arnold Levine at the Institute for Advanced Study, Princeton, the estrogen binds more strongly, resulting in far greater production of the MDM2 protein. Women with higher estrogen levels and who also have the genetic variation would be expected to have higher estrogen-related MDM2 protein that could increase their melanoma risk, explains Dr. Polsky.
Scientists have shown that the substitution of a single letter of DNA at a specific point in the MDM2 promoter can significantly ramp up gene production. The new study evaluated the effects of this natural genetic variation in 227 melanoma patients enrolled in NYU's Interdisciplinary Melanoma Cooperative Group between August 2002 and November 2006. Dr. Polsky and colleagues from NYU School of Medicine recorded each patient's MDM2 and p53 genetic variations, as well as age, sex, personal and family history of melanoma, and tumor thickness. The results showed that more than 40 percent of women diagnosed with melanoma under the age of 50 had the genetic variation in the MDM2 gene promoter. In contrast, only about 16 percent of women diagnosed after the age of 50 had the variation. The new study was released online March 24, 2009, in the journal Clinical Cancer Research and will be published in the April 1, 2009, issue of the journal.
