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Gene determines tanning response and melanoma risk
By Bijal P. Trivedi

"Slip, Slop, Slap," is the slogan of an Australian skin cancer awareness campaign that has been going strong for well over a decade. The campaign encourages Australians, who have the highest rates of skin cancer in the world, to "slip on a shirt, slop on sunscreen, and slap on a hat" before braving the southern rays. It's particularly good advice, says Australian researcher Richard Sturm, whose recent study shows that a person's skin color and potential to tan is heavily influenced by the particular variants of the melanocortin-1 receptor (MCR-1) gene. Genetic testing could help people gauge the risk of developing melanoma and modify time spent in the sun, says Sturm. He presented his results at the annual meeting of the American Society of Human Genetics, in Philadelphia.

MCR-1 is the switch that controls the tanning response, says Sturm, of the University of Queensland. The most common version, or wild type, of the gene allows immature yellow and red pigment molecules to be chemically altered to become brown and black—people with two copies of wild type MCR-1 are able to tan and are not as susceptible to skin cancers.

Three variants of MCR-1—R151C, R160W and D294H—block the transformation of the pigment molecules. People with one of the variants and one wild type are able to get a moderate tan. But those with two variants are at the greatest risk for melanoma, says Sturm.

Having two variant forms of MCR-1 is strongly associated with red hair, blue eyes, and fair skin. These people have high mole counts, cannot tan but instead burn and freckle in the sun and have a four to five-fold increased risk of melanoma compared to the general Australian population.

However, the people who need to be most cautious, believes Sturm, are those who have one wild type gene and one variant. These people tend to over-rate their ability to tan, and increase their risk of melanoma by spending excessive amounts of time in the sun.

Sturm's study is the largest one to date. The study examines the MCR-1 gene type in 459 melanoma patients and 399 control individuals and correlates the data with the risk factor. He also thinks there is a need to classify skin color using genetic criteria rather than the use of self-observation, which could lead to under-estimates of melanoma risk.

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Sturm, R.A. et al. Melanocortin-1 receptor genotype is a risk factor for basal cell carcinoma, squamous cell carcinoma and melanoma. Am J Hum Genet 67, supplement to volume 67, 16 (October 2000).

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