Genetics of Skin Pigment and Cancer

Experience shows that people with fair complexions (low levels of melanin) are more prone to sunburn. New research now reveals that certain variations in the genes that control the color of our skin, hair and eyes are associated with an increased risk of melanoma and carcinoma, two potentially deadly forms of skin cancer. Here is a summary of what these three new studies on the genetic variants and skin cancer revealed.

* Genes Associated with Fair Color and Skin Cancer *

Daniel Gudbjartsson, Patrick Sulem and a throng of other researchers published the article “ASIP and TYR pigmentation variants associate with cutaneous melanoma and basal cell carcinoma,” the results of which indicate that fair coloration increases the risk of developing cutaneous melanoma (CM) and basal cell carcinoma (BCC).

Previously published genome-wide association studies have identified some of the allele variations associated with the hair, eye and skin pigmentation of Europeans. This new study assessed the effect of these variants on risk of CM and BCC in European populations. The sample studied included 2,121 subjects with CM, 2,163 with BCC and more than 40,000 controls.

The genetic variants associated with three sections of genes were found to be linked with increased risk of skin cancer.
The variant of the TYR gene that encodes a R402Q amino acid substitution previously shown to affect eye color and tanning response, was, in this study, associated with increased risk of developing CM and BCC. Variations in a haplotype (set of closely associated genes) near the ASIP gene, known to affect pigmentation traits, conferred significant risk of CM and BCC. An eye color variant in gene TYRP1 was also associated with risk of CM.

* Genome-wide Association Studies *

Many scientists and research groups are now carrying out genome-wide association studies, which involve rapidly scanning markers (DNA sequences used to identify a particular location on a chromosome) across the genomes of many people to find genetic variations associated with a particular disease.

Since 2005, studies employing this gene-scanning technique have discovered approximately 100 DNA variants to 40 common diseases and traits, including prostate cancer, heart disease, multiple sclerosis, gallstones and restless leg syndrome, to name just a few. We can now add the genetic variants associated with skin cancer to the list.
* Genome-wide Association Study of Pigmentation Genes *

Gudbjartsson and Sulem also announced another research project, this one a genome-wide association study titled, ‘Two newly identified genetic determinants of pigmentation in Europeans.’ Genetic variants associated with human pigmentation characteristics were examined among a sample of more than 5,000 Icelanders. Two coding variants in TPCN2 gene were associated with hair color, and a variant at the ASIP locus showed a strong relationship with skin sensitivity to sun, freckling and red hair.

* Genetic Variations in Chromosome 20 Associated with Melanoma *

Kevin M Brown, Stuart MacGregor and about 40 other researchers unveiled another genome-wide association study, titled “Common sequence variants on 20q11.22 confer melanoma susceptibility.” This study identified a new melanoma risk locus on chromosome 20.

* Knowing Your Skin Cancer Risk *

Being aware of genetic variants that increase the risk of certain diseases does not mean that we know how to cure or prevent these illnesses; at least not yet. But once genetic links are identified, researchers can use the information to develop better strategies to detect, treat and prevent the disease. In the case of genetic variations associated with skin cancer, knowledge is power. Knowing that you are at increased risk can help you to take the necessary precautions to protect yourself from the sun’s skin damaging rays.

Here are some sites with helpful information on being sun-smart this summer:

Kids Health – How to Be Safe When You’re In the Sun

Centers fro Disease Control – Play It Safe in the Sun

American Academy of Dermatology – Safe Sun Tips

* Sources *

Gudbjartsson, D., Sulem P. et al. “ASIP and TYR pigmentation variants associate with cutaneous melanoma and basal cell carcinoma.” Nature Genetics (18 May 2008), 161, Letters

Sulem P., Gudbjartsson, D. et al. “Two newly identified genetic determinants of pigmentation.” Europeans Nature Genetics (18 May 2008), 160, Brief Communications

Brown, K., McGregor, S. et al. “Common sequence variants on 20q11.22 confer melanoma susceptibility.” Nature Genetics (8 May 2008), 163, Brief Communications