In two papers published today, deCODE scientists and academic colleagues from Europe and the U.S. expand 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.
In the first paper, utilizing 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 signaling 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% of the population does -- was shown to correspond to a 45% increase in risk of CM and 33% increase in risk of BCC compared to non-carriers. Each copy of the TYR variant, of which 35% of people carry at least one copy, was found to confer a 20% increased risk of CM and a 14% 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.