Skin colour and skin cancer

The team from Iceland's deCODE Genetics that identified sequence variations influencing hair, eye and skin pigmentation have found two more genetic determinants and two variants that confer an increased risk of melanoma.

The studies were published today in Nature Genetics, along with an Australian study identifying a new melanoma risk locus.

In October last year, deCODE reported novel single nucleotide polymorphisms (SNPs) influencing skin, eye and hair colour in Europeans.

They found that a SNP on chromosome 14 in the SLC24A4 gene is associated with an increased likelihood of blond rather than brown hair, and blue rather than green eyes. Blonde hair is also associated with a variant near the KITLG gene on chromosome 12.

A SNP on chromosome 6 is associated with freckles, as is a SNP in the tyrosinase (TYR) gene.

The team also confirmed previous studies associating red hair, freckles and sun sensitivity with the MC1R gene, and other variants near the OCA2 gene with eye and hair colour.

In the new studies, the team found a variant in the ASIP (encoding agouti signalling protein) gene, which has a well-documented role in pigmentation, which was very similar to those observed in MC1R. They also found two coding variants in TPCN2 that are associated with blond versus brown hair.

Importantly for skin cancer research, the team has found a haplotype near ASIP confers a significant risk of cutaneous melanoma, the highly aggressive cancer that causes the majority of deaths, and a risk of basal cell carcinoma, the more common but less deadly cancer.

A variant on TYR also conferred a risk of cutaneous melanoma and basal cell carcinoma.

In an independent study, Stuart McGregor, from the Queensland Institute of Medical Research, and colleagues found two SNPs on chromosome 20 conferred a risk of cutaneous melanoma. The SNPs are located in the region of ASIP but the team believes there are several other candidate loci.

deCODE papers: DOI: 10.1038/ng.160 and DOI: 10.1038/ng.161 MacGregor paper: DOI: 10.1038/ng.163