More than a hundred studies have proposed gene alterations that may be associated with the risk of melanoma skin cancer. Now, the first comprehensive analysis of these studies has identified just five genetic variants that are statistically significantly associated with melanoma at the genome-wide level and strongly backed by epidemiologic evidence. The study was published online June 21st in the Journal of the National Cancer Institute.

To assess the accumulated evidence linking specific genetic variants to cutaneous melanoma (CM), Alexander J. Stratigos, M.D., of the University of Athens Medical School in Greece and colleagues collected and catalogued all genetic association studies published in the melanoma field, including genome wide association studies. In a joint collaborative project with other international institutions, the authors conducted a systematic meta-analysis for each genetic variant identified. For those variants that had statistically significant results in the meta-analysis, they also graded the epidemiologic evidence supporting their association with melanoma.

Starting with 745 variants, the authors narrowed down their search to 19 in eight different chromosomal locations, or loci, with statistically significant associations with melanoma. Four of these loci were identified in the main meta-analyses and Stratigos and colleagues found strong epidemiologic support for an association between these genetic variants and melanoma. Supplementary analyses identified variants at one more location that met these criteria.

The loci having the strongest associations with melanoma susceptibility contained genes that play an important role in determining skin, hair, and eye color. However, the authors note that this finding has to be interpreted with caution because these loci were chosen in the first place, i.e., for testing in the original studies, because of their effect on pigmentation, which is known to be associated with melanoma risk.

The evidence accumulated for this study has been reported on the publicly accessible, regularly updated MelGene website, which provides a potential forum to report genes associated with CM as they are identified.

"In summary," the authors write, "we present a systematic and comprehensive assessment of the current evidence of genetic epidemiology research in CM. The putative risk factors that have emerged from the meta-analyses—accessible on MelGene—represent the most promising CM susceptibility genes described to date."

Source: JNCI

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