GenoMEL, the Melanoma Genetics Consortium, has been in existence for 13 years. One of GenoMEL's research aims is to identify melanoma susceptibility genes. Ten percent of melanoma cases result from an inherited predisposition for which high penetrance melanoma genes seem to be responsible. Germline mutations in the CDKN2A gene, which encodes two proteins (p16 and p14ARF), are the most common cause of inherited susceptibility to melanoma, however they account for only 20-25% of families with multiple cases of melanoma.
Since the hunt for high risk melanoma genes has not revealed a single gene anymore since 1996, GenoMEL continued their search for genes by a Single Nucleotide Polymorphism (SNP) based genome wide association study in 1650 sporadic melanoma cases and 4336 controls throughout Europe and Australia; this time to identify low penetrance genes rather than high penetrance genes.
Interestingly, among the SNPs found to be associated with melanoma risk were SNPS in or near genes affecting skin pigmentation such as MC1R, ASIP, TYR and TYRP1. The associations remained significant even after adjustment for the effect of pigmentation.
The corresponding associated odds ratios (ranging from 1.15-1.45) seem to be small, but taking into account that melanoma is a polygenic trait, combined genetic variants in these pigmentation genes could add-up significantly to melanoma risk.
It is remarkable to see that phenotypic characteristics that have been clinically linked to melanoma for decades are now explained and confirmed on the genetic level and that for the same token these underlying genetic determinants have become definite key players in melanoma predisposition irrespective of their effects on pigmentation.