Melanoma is a rare but deadly form of skin cancer. Known risk factors include pale skin, large numbers of moles (also known as nevi), and prolonged sun exposure. Nevus count has a strong genetic component and researchers have already identified some genetic variants that influence the trait. In a new study published in American Journal of Human Genetics, an international team of scientists led by David Duffy and Grant Montgomery reports a genetic variant newly associated with nevus count and melanoma risk, but with an interesting twist.
When Duffy’s team examined data from about 2,000 adolescents of European ancestry living in Australia, they found that each copy of a T at variant rs12203592 was associated with a significant increase in numbers of “flat” nevi (the most common type of nevus). When they looked at data from the parents of the adolescents, however, they saw no such effect. In fact, the data suggested that the C version of rs12203592 – not the T version – was associated with higher nevus counts in older people. Comparing these results with data from thousands of individuals from the UK confirmed the differing age-dependent effects of rs12203592.
(23andMe Complete Edition customers can check their data for rs12203592 using the Browse Raw Data feature.)
To investigate whether rs12203592 also influences risk for melanoma, the researchers analyzed data from approximately 3,500 individuals with melanoma and over 5,000 healthy individuals, all of European ancestry. The C version of rs12203592 was associated with 1.15 times higher odds of disease, but when they restricted the analysis based on the location of the melanoma, the association was only significant for melanomas on the trunk (main torso). Each copy of a C led to about 1.3 times higher odds of truncal melanoma.
The mechanisms connecting rs12203592 to melanoma risk are not yet fully understood. While the T version of rs12203592 has been associated with traits typically considered risk factors for melanoma (pale skin, dark hair, and freckling), this study suggests that the T version actually protects against the disease. The observation of age-dependent effects on nevus counts adds more wrinkles to the story. Duffy and his colleagues posit that individuals with a T at rs12203592 are more likely to develop large numbers of moles early in life, but that these moles tend to disappear with age. More research will be needed to determine the relationship between age-dependent patterns of nevus counts and melanoma risk.
SNPwatch gives you the latest news about research linking various traits and conditions to individual genetic variations. These studies are exciting because they offer a glimpse into how genetics may affect our bodies and health; but in most cases, more work is needed before this research can provide information of value to individuals. For that reason it is important to remember that like all information we provide, the studies we describe in SNPwatch are for research and educational purposes only. SNPwatch is not intended to be a substitute for professional medical advice; you should always seek the advice of your physician or other appropriate healthcare professional with any questions you may have regarding diagnosis, cure, treatment or prevention of any disease or other medical condition.