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News

deCODE reveals novel genetic links and skin cancer links

DeCODE Genetics : 19 May, 2008  (Company News)
deCODE scientists and academic colleagues from Europe and the USA have expanded upon the company's recent findings in the genetics of pigmentation traits in people of European descent, and demonstrate that certain of these common variants also confer risk of two types of skin cancer.
Utilising genomic analysis of nearly 8,500 Icelandic and Dutch participants, the deCODE team identified a novel, tightly-linked pair of single-letter variants (SNPs) near the ASIP (agouti signalling protein) gene on chromosome 20 that greatly increase the likelihood of an individual being prone to freckles and sunburn. A SNP in the TYR (tyrosinase) gene on chromosome 11, previously linked by deCODE to eye color, was here shown also to confer susceptibility to sunburn. Both ASIP and TYR are known to play a role in pigmentation.

Because very fair skin, blue or green eyes, freckles, red hair, and exposure to ultraviolet light are all known risk factors for skin cancer, in the second paper the deCODE team set out to investigate whether the variants it had linked to pigmentation traits also associated with risk of cutaneous melanoma (CM) and basal cell carcinoma (BCC).

CM is the most dangerous form of skin cancer, while BCC is very common but does not frequently spread to other parts of the body. In case-control and replication studies involving a total of some 45,000 CM and BCC patients and control subjects from Iceland, Sweden, Spain, Hungary, Romania and Slovakia, carrying one set of the ASIP variants - which 15 percent of the population does - was shown to correspond to a 45 percent increase in risk of CM and 33 percent increase in risk of BCC compared to non-carriers.

Each copy of the TYR variant, of which 35 percent of people carry at least one copy, was found to confer a 20 percent increased risk of CM and a 14 percent increase in risk of BCC compared to non-carriers. These increases in risk remain significant even after accounting for the effect of the pigmentation traits themselves on cancer risk. Furthermore, several other variants that deCODE has also linked to freckling and sensitivity to sun did not show any detectable link to skin cancer.

'It is common knowledge that people with fairer complexions tend to be more sensitive to the sun, and that extensive exposure to sun or repeated burning can increase the risk of skin cancers. But we are now showing that there are a variety of different genetic bases for what appear to be the same pigmentation characteristics, and we have demonstrated that certain of these carry with them greater risk of skin cancer than do others.

This information is important for understanding the biology of skin cancers, particularly as it appears that these variants may be conferring some of this additional risk through a mechanism independent of their role in giving rise to sun-sensitive skin. These findings may also be useful for helping individuals to better gauge their susceptibility to skin cancer, and we are therefore very pleased to be including these variants in our deCODEme service,' said Kari Stefansson, chief executive officer of deCODE.

The two papers from the studies, 'Two newly identified genetic determinants of pigmentation in Europeans' and 'ASIP and TYR pigmentation variants associate with cutaneous melanoma and basal cell carcinoma,' are published in the online edition of Nature Genetics.

The research was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, by a subcontract agreement to deCODE Genetics under Westat contract N02-CP-91026 to the National Cancer Institute. The Swedish portion of the study received financial support from the Swedish Cancer Society, the Radiumhemmet Research Funds and the Swedish Research Council.
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