Researchers have identified five genetic variants that appear to be the most promising markers of susceptibility for melanoma from a set of 745 variants that have been linked to the disease in published studies. The results of this meta-analysis, which included 145 genetic association studies in melanoma, appeared online June 21 in the Journal of the National Cancer Institute.
Each of the five variants showed a statistically significant association with melanoma at the genome-wide level and had “strong epidemiological credibility,” Dr. Alexander Stratigos of the University of Athens Medical School in Greece and his colleagues found.
To conduct the analysis, the researchers collected and catalogued all genetic association studies published in the field of melanoma, including results from recent genome-wide association studies. Working with colleagues around the world, they then conducted a systematic meta-analysis for each genetic variant identified. For each variant that showed a statistically significant association with melanoma in the meta-analysis, the authors also assessed the epidemiologic evidence supporting such an association.
The strongest associations with melanoma included variants within genes that play an important role in determining the color of skin, hair, and eyes. This finding may reflect the fact that these variants had been tested in the original candidate gene studies precisely because of their effects on pigmentation, a well-known risk factor of melanoma, the study authors noted.
Nonetheless, the confirmation of some of these variants in genome-wide association studies“strongly supports their contribution to melanoma susceptibility,” Dr. Stratigos wrote in an e-mail. “Whether their effect on melanoma risk is exclusively through their influence on pigmentation, or also partly independent of that, cannot be assessed with our systematic meta-analysis approach,” he added.
The results provide “an integrated perspective of the accumulated evidence of genetic associations” in melanoma, the authors concluded. Their evidence is available online at the MelGene Database, which provides “a regularly updated field synopsis of genetic association studies performed in melanoma,” according to the site.
NCI Cancer Bulletin for June 28, 2011 - National Cancer Institute
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